Fiche société
Hospices Civils de Lyon
Traitements, essais et publications liés.
Traitements20programmes
Essais7liés
Publications30liées
SourceDBlocale
Traitements
20| Molécule | Indication / population | Phase | Objectif | Pays | Résultat |
|---|---|---|---|---|---|
| 1 Hypercapnic challenge while participant is awakeDespite the continuous development of new antiseizure medications over the past 25 years, 30% of patients with epilepsy suffer from drug-resistant seizures and are at risk of epilepsy-related complications, like cognitive dysfunctions, sleep-disordered breathing or Sudden and Unexpected Death in Epilepsy (SUDEP). SUDEP typically occurs during sleep, after a nocturnal seizure, and primarily results from a postictal central respiratory dysfunction in patients with generalized convulsive seizure (GCS), suggesting that interaction between respiratory dysfunction and sleep state may play a role in its pathophysiology. Post-mortem data in SUDEP patients showed alteration of neuronal populations involved in respiratory control in the medulla. Accordingly, pharmacologic strategies aimed at reducing the severity of postictal respiratory dysfunction has appeared as one of the most promising way to prevent SUDEP. However, no encouraging result has hitherto been reported. Interconnections between the complex network that regulates arousal and sleep and the respiratory network are numerous. They primarily include the relation between chemosensitive regulation and arousal system to ensure asphyxia-induced arousal (i.e. arousal to elevated CO2), especially through serotonin (5HT)-dependent connections in brain stem. The link between alterations of the brainstem networks involved in arousal regulation and respiratory dysfunction has not been characterized in patients with epilepsy yet. Like 5HT, adenosine is deeply implicated in the regulation of sleep and central respiratory control. Seizures transiently increase adenosine extracellular levels. Adenosine physiological effects in the brain are mediated through the activation of two types of Adenosine receptors (ARs), A1Rs and A2ARs. Extracellular adenosine promotes sleep via A1R-dependant inhibition of glutamatergic neurons in the basal forebrain, but also via A2AR-dependant activation of neurons in the nucleus accumbens. Respiration is also inhibited by A1R and A2AR. Most importantly, it has been shown that drug-resistant epilepsy is associated with long-term alterations of ARs cortical expression. However, whether or not a similar epilepsy-related plasticity of ARs occurs in the brainstem and may participate to chronic arousal and respiratory dysfunction in epilepsy has never been investigated. Considering the tight interplay between central respiratory control, arousal regulation and brainstem adenosine, the main hypothesis of the BRAVE study is that epilepsy might result in alterations of the distribution of A1Rs in the brainstem structures involved in respiratory regulation and/or arousal control, especially in the brainstem structures involved in respiratory regulation under hypercapnic condition. The study combines clinical respiratory characterization, morphological, functional and metabolic imaging, using the hybrid simultaneous 3T MRI-PET scanner (Siemens Biograph mMR) of the CERMEP. Combining PET with anatomical and functional MR imaging enables non-invasively in vivo mapping of receptor binding and functional neuronal assessment of a physiological task in the entire brain with high spatial resolution. Investigators already performed fMRI study of respiratory centers, showing number of functional changes in brainstem regions participating to the central control of respiration, including reduced activation during breath-holding fMRI, in patients with epilepsy. The BRAVE study will use the same respiratory paradigm as the one used in this past study. PET imaging will be focused on A1R, using \[18F\]CPFPX, a selective A1R antagonist. | Épilepsie | Non applicable | À vérifier | France | À vérifier |
| biological samplesSystemic autoimmune diseases associated with type I interferon (IFN-I) dysregulation, such as systemic lupus erythematosus, systemic sclerosis, myositis, and mixed or undifferentiated connective tissue diseases, and genetic type 1 interferonopathies are characterized by chronic and excession IFN-I signaling and production contributing to disease pathogenesis. Aberrant IFN-I production can be triggered through the activation of multiple signaling pathways, particularly those involving intracellular and extracellular RNA and DNA sensing receptors. We hypothesize that excessive IFN-I production results from an increased tonic activation state of nucleic acid sensors and/or an enhanced responsiveness of these sensors to endogenous nucleic acids, thereby sustaining pathological IFN-I signaling and chronic inflammation. The aim of this study is to characterize the type I interferon (IFN-I) response, defined by both the IFN-I gene signature and plasma IFN-α levels, following stimulation with a panel of ligands specific for DNA- and RNA-sensing pathways. | Lupus, Myopathies | Non applicable | Immunomodulation | France | À vérifier |
| Cardio-respiratory monitoring30% of patients with epilepsy suffer from drug-resistant seizures and have a greater risk of premature mortality than the general population. Among all causes of death, the most frequent is SUDEP, for sudden and unexpected death in epilepsy patients. SUDEP typically occurs after a nocturnal seizure, and primarily results from a postictal central respiratory dysfunction in patients with generalized convulsive seizure (GCS), suggesting the critical role of seizure-related impairment of breathing control, and underscoring the importance of monitoring and preventive interventions during the post-ictal phase. Most of patients with drug-resistant seizures demonstrate transient peri-ictal apnea and hypoxemia especially in the aftermath of a GCS. Experimental and clinical data suggest that most SUDEP primarily result from a fatal seizure-related respiratory arrest 5. Apnea was the primary cause of death in several epilepsy models. In patients whose SUDEP had occurred during long-term video-EEG monitoring, we observed fatal postictal central apnea after a nocturnal GCS in all SUDEP. Accordingly, it is currently hypothesized that in a subgroup of patients, repetition of seizures may contribute to chronic alteration of respiratory regulation which may increase the risk of fatal postictal central respiratory arrest. Central regulation of autonomic function is ensured by the so-called Central Autonomic Network (CAN), which anatomy in humans has primarily been investigated in neuroimaging studies or using intraEEG (iEEG) data in patients with drug-resistant focal epilepsy undergoing presurgical evaluation with intracerebral electrodes. Central regulation of breathing primarily rely on brainstem, especially the preBötzinger complex for rhythm generation and the retrotrapezoid nucleus and dorsal raphe for chemoreception, especially ventilatory response to hypercapnia. However, through an intricated structures connecting these regions, this respiratory signal projects to a network of cortical and subcortical regions mainly including the limbic and sensorimotor cortical areas. Studies in patients undergoing iEEG reinforced the role of limbic and paralimbic structures, with transient central apnea elicited by direct electrical stimulation of amygdala, hippocampus, anterior parahippocampal, and antero-mesial fusiform gyri. However, our group also reported transient hypoxemia could be elicited by cortical direct electrical stimulation outside the temporo-limbic structures, most commonly after stimulation of the perisylvian cortex. Importantly, our group recently showed that involvement of this perisylvian cortex in the epileptogenic zone is a strong risk factor of SUDEP, reinforcing the importance of further studying its integration in the cortical control of respiration. The involvement of cortical control of ventilation is particularly important to ensure expiratory load compensation, a typical situation after GCS, which is associated with airway obstruction, especially when the face is positioned into the pillow. This cortical component of the physiological response to experimental expiratory loads was investigated in healthy subjects through the study of EEG activity during an expiratory load compensation protocol. Accordingly, EEGs were processed by ensemble averaging expiratory time-locked segments and examined for pre-expiratory EEG potentials, defined as a slow negative shift from the baseline signal preceding expiration, and suggestive of cortical preparation of expiration. Expiratory load compensation was associated with EEG premotor potential presumably involving the supplementary motor area. However, because of the limited spatial resolution of scalp EEG, the organization of cortical neural sources involved in this expiratory load compensation or during response to hypercapnia, especially the interaction between the premotor cortex, the sensorimotor cortical areas and the perisylvian cortex is unknown. | Épilepsie | Non applicable | À vérifier | France | À vérifier |
| Comprehensive respiratory monitoring30% of patients with epilepsy suffer from drug-resistant seizures and have a greater risk of premature mortality than the general population. Among all causes of death, the most frequent is SUDEP, for sudden and unexpected death in epilepsy patients. SUDEP typically occurs after a nocturnal seizure, and primarily results from a postictal central respiratory dysfunction in patients with generalized convulsive seizure (GCS), suggesting the critical role of seizure-related impairment of breathing control, and underscoring the importance of monitoring and preventive interventions during the post-ictal phase. Most of patients with drug-resistant seizures demonstrate transient peri-ictal apnea and hypoxemia especially in the aftermath of a GCS. Experimental and clinical data suggest that most SUDEP primarily result from a fatal seizure-related respiratory arrest 5. Apnea was the primary cause of death in several epilepsy models. In patients whose SUDEP had occurred during long-term video-EEG monitoring, we observed fatal postictal central apnea after a nocturnal GCS in all SUDEP. Accordingly, it is currently hypothesized that in a subgroup of patients, repetition of seizures may contribute to chronic alteration of respiratory regulation which may increase the risk of fatal postictal central respiratory arrest. Central regulation of autonomic function is ensured by the so-called Central Autonomic Network (CAN), which anatomy in humans has primarily been investigated in neuroimaging studies or using intraEEG (iEEG) data in patients with drug-resistant focal epilepsy undergoing presurgical evaluation with intracerebral electrodes. Central regulation of breathing primarily rely on brainstem, especially the preBötzinger complex for rhythm generation and the retrotrapezoid nucleus and dorsal raphe for chemoreception, especially ventilatory response to hypercapnia. However, through an intricated structures connecting these regions, this respiratory signal projects to a network of cortical and subcortical regions mainly including the limbic and sensorimotor cortical areas. Studies in patients undergoing iEEG reinforced the role of limbic and paralimbic structures, with transient central apnea elicited by direct electrical stimulation of amygdala, hippocampus, anterior parahippocampal, and antero-mesial fusiform gyri. However, our group also reported transient hypoxemia could be elicited by cortical direct electrical stimulation outside the temporo-limbic structures, most commonly after stimulation of the perisylvian cortex. Importantly, our group recently showed that involvement of this perisylvian cortex in the epileptogenic zone is a strong risk factor of SUDEP, reinforcing the importance of further studying its integration in the cortical control of respiration. The involvement of cortical control of ventilation is particularly important to ensure expiratory load compensation, a typical situation after GCS, which is associated with airway obstruction, especially when the face is positioned into the pillow. This cortical component of the physiological response to experimental expiratory loads was investigated in healthy subjects through the study of EEG activity during an expiratory load compensation protocol. Accordingly, EEGs were processed by ensemble averaging expiratory time-locked segments and examined for pre-expiratory EEG potentials, defined as a slow negative shift from the baseline signal preceding expiration, and suggestive of cortical preparation of expiration. Expiratory load compensation was associated with EEG premotor potential presumably involving the supplementary motor area. However, because of the limited spatial resolution of scalp EEG, the organization of cortical neural sources involved in this expiratory load compensation or during response to hypercapnia, especially the interaction between the premotor cortex, the sensorimotor cortical areas and the perisylvian cortex is unknown. | Épilepsie | Non applicable | À vérifier | France | À vérifier |
| ENHANCED MEDICAL TREATMENTType 2 cardio renal syndrome is defined by the occurrence or the exacerbation of a kidney failure induced by a chronic heart failure. Sodium overload is one of the main causes leading to the occurrence or the exacerbation of this syndrome. Some patients have a massive sodium retention on which medications are not effective enough. These patients have no further therapeutic options because of the refractory congestion and a 3-months mortality rate around 15%, frequent rehospitalization (3-months rehospitalization rate at 71%) and an excessively impaired quality of life. For those refractory heart failure with cardio renal syndrome, nephrology departments resort to non-medication sodium extraction (hemodialysis, peritoneal dialysis, isolated ultrafiltration). Between 2002 and 2008, 927 French patients would have start dialysis in this situation. In 2013, 174 patients start dialysis in 97 dialysis centers. French National Authority of Health recently published new Good Practice Guidance thereupon, strengthened by the increasing number of publications and the widespread use of this technique. There is therefore a consensus among professionals about the benefits of such a technique in those indications. However, bibliographical data are not strong enough to support a strong level of evidence. None of foresight strategies have been compared to others in a proper randomized controlled trial, and there is no clue about any suspected superiority from one strategy to another. So far, the investigators propound invasive, expensive and not validated techniques to patients with functional and vital prognosis altered. The investigators think it's essential to prove the efficacy of such an approach. They wish to quantify those techniques impact on rehospitalization, with a consideration for the potential survival impact. It seems unethical to evaluate separated techniques, taking in account that patients with severe heart failure will switch from one technique to another among their care. It is therefore crucial to validate benefits from an invasive procedure (hemodialysis, peritoneal dialysis, isolated ultrafiltration) compared to a medication-restricted care. | Insuffisance cardiaque | Non applicable | À vérifier | France | À vérifier |
| estradiolMultiple sclerosis (MS) affects 1 in 1000 people in western countries, mainly women in their childbearing years. It is an autoimmune disease of the central nervous system (CNS), which results in a chronic focal inflammatory response with subsequent demyelination and axonal loss. Recent prospective studies reported a significant decline by two-thirds in the rate of relapses during the third trimester of pregnancy and a significant increase by two-thirds during the first three months post-partum by comparison to the relapse rate observed during the year prior to the pregnancy (Confavreux et al., 1998). These dramatic changes in the relapse rate occur at a time when the impregnation of many substances (among which, sexual steroids) is at its highest, before a dramatic decline to the pre-pregnancy levels, immediately following delivery. It may be hypothesized that sexual steroids could exert beneficial effects through a modulation of the immune state with a lowering of the pro-inflammatory lymphocyte responses of the Th1 type and an enhancement of the anti-inflammatory responses of the Th2 type. They may also play a direct role in the remyelination of central nervous system lesions, as they do in the peripheral nervous system. The POPART'MUS study is a European, multicentre, randomized, placebo-controlled and double-blind clinical trial, which aims to prevent MS relapses related to the post-partum condition, by administering high doses of progestin (nomegestrol acetate), in combination with endometrial protective doses of estradiol. Treatment will be given immediately after delivery and continuously during the first three months post-partum. Assuming the results of the trial to be positive, this new treatment could be considered in the relapsing-remitting phase of the disease in women afar from pregnancy and post-partum. | SEP | Phase 3 | Remyélinisation | France | À vérifier |
| Expiratory load compensation30% of patients with epilepsy suffer from drug-resistant seizures and have a greater risk of premature mortality than the general population. Among all causes of death, the most frequent is SUDEP, for sudden and unexpected death in epilepsy patients. SUDEP typically occurs after a nocturnal seizure, and primarily results from a postictal central respiratory dysfunction in patients with generalized convulsive seizure (GCS), suggesting the critical role of seizure-related impairment of breathing control, and underscoring the importance of monitoring and preventive interventions during the post-ictal phase. Most of patients with drug-resistant seizures demonstrate transient peri-ictal apnea and hypoxemia especially in the aftermath of a GCS. Experimental and clinical data suggest that most SUDEP primarily result from a fatal seizure-related respiratory arrest 5. Apnea was the primary cause of death in several epilepsy models. In patients whose SUDEP had occurred during long-term video-EEG monitoring, we observed fatal postictal central apnea after a nocturnal GCS in all SUDEP. Accordingly, it is currently hypothesized that in a subgroup of patients, repetition of seizures may contribute to chronic alteration of respiratory regulation which may increase the risk of fatal postictal central respiratory arrest. Central regulation of autonomic function is ensured by the so-called Central Autonomic Network (CAN), which anatomy in humans has primarily been investigated in neuroimaging studies or using intraEEG (iEEG) data in patients with drug-resistant focal epilepsy undergoing presurgical evaluation with intracerebral electrodes. Central regulation of breathing primarily rely on brainstem, especially the preBötzinger complex for rhythm generation and the retrotrapezoid nucleus and dorsal raphe for chemoreception, especially ventilatory response to hypercapnia. However, through an intricated structures connecting these regions, this respiratory signal projects to a network of cortical and subcortical regions mainly including the limbic and sensorimotor cortical areas. Studies in patients undergoing iEEG reinforced the role of limbic and paralimbic structures, with transient central apnea elicited by direct electrical stimulation of amygdala, hippocampus, anterior parahippocampal, and antero-mesial fusiform gyri. However, our group also reported transient hypoxemia could be elicited by cortical direct electrical stimulation outside the temporo-limbic structures, most commonly after stimulation of the perisylvian cortex. Importantly, our group recently showed that involvement of this perisylvian cortex in the epileptogenic zone is a strong risk factor of SUDEP, reinforcing the importance of further studying its integration in the cortical control of respiration. The involvement of cortical control of ventilation is particularly important to ensure expiratory load compensation, a typical situation after GCS, which is associated with airway obstruction, especially when the face is positioned into the pillow. This cortical component of the physiological response to experimental expiratory loads was investigated in healthy subjects through the study of EEG activity during an expiratory load compensation protocol. Accordingly, EEGs were processed by ensemble averaging expiratory time-locked segments and examined for pre-expiratory EEG potentials, defined as a slow negative shift from the baseline signal preceding expiration, and suggestive of cortical preparation of expiration. Expiratory load compensation was associated with EEG premotor potential presumably involving the supplementary motor area. However, because of the limited spatial resolution of scalp EEG, the organization of cortical neural sources involved in this expiratory load compensation or during response to hypercapnia, especially the interaction between the premotor cortex, the sensorimotor cortical areas and the perisylvian cortex is unknown. | Épilepsie | Non applicable | À vérifier | France | À vérifier |
| Hypercapnic challenge30% of patients with epilepsy suffer from drug-resistant seizures and have a greater risk of premature mortality than the general population. Among all causes of death, the most frequent is SUDEP, for sudden and unexpected death in epilepsy patients. SUDEP typically occurs after a nocturnal seizure, and primarily results from a postictal central respiratory dysfunction in patients with generalized convulsive seizure (GCS), suggesting the critical role of seizure-related impairment of breathing control, and underscoring the importance of monitoring and preventive interventions during the post-ictal phase. Most of patients with drug-resistant seizures demonstrate transient peri-ictal apnea and hypoxemia especially in the aftermath of a GCS. Experimental and clinical data suggest that most SUDEP primarily result from a fatal seizure-related respiratory arrest 5. Apnea was the primary cause of death in several epilepsy models. In patients whose SUDEP had occurred during long-term video-EEG monitoring, we observed fatal postictal central apnea after a nocturnal GCS in all SUDEP. Accordingly, it is currently hypothesized that in a subgroup of patients, repetition of seizures may contribute to chronic alteration of respiratory regulation which may increase the risk of fatal postictal central respiratory arrest. Central regulation of autonomic function is ensured by the so-called Central Autonomic Network (CAN), which anatomy in humans has primarily been investigated in neuroimaging studies or using intraEEG (iEEG) data in patients with drug-resistant focal epilepsy undergoing presurgical evaluation with intracerebral electrodes. Central regulation of breathing primarily rely on brainstem, especially the preBötzinger complex for rhythm generation and the retrotrapezoid nucleus and dorsal raphe for chemoreception, especially ventilatory response to hypercapnia. However, through an intricated structures connecting these regions, this respiratory signal projects to a network of cortical and subcortical regions mainly including the limbic and sensorimotor cortical areas. Studies in patients undergoing iEEG reinforced the role of limbic and paralimbic structures, with transient central apnea elicited by direct electrical stimulation of amygdala, hippocampus, anterior parahippocampal, and antero-mesial fusiform gyri. However, our group also reported transient hypoxemia could be elicited by cortical direct electrical stimulation outside the temporo-limbic structures, most commonly after stimulation of the perisylvian cortex. Importantly, our group recently showed that involvement of this perisylvian cortex in the epileptogenic zone is a strong risk factor of SUDEP, reinforcing the importance of further studying its integration in the cortical control of respiration. The involvement of cortical control of ventilation is particularly important to ensure expiratory load compensation, a typical situation after GCS, which is associated with airway obstruction, especially when the face is positioned into the pillow. This cortical component of the physiological response to experimental expiratory loads was investigated in healthy subjects through the study of EEG activity during an expiratory load compensation protocol. Accordingly, EEGs were processed by ensemble averaging expiratory time-locked segments and examined for pre-expiratory EEG potentials, defined as a slow negative shift from the baseline signal preceding expiration, and suggestive of cortical preparation of expiration. Expiratory load compensation was associated with EEG premotor potential presumably involving the supplementary motor area. However, because of the limited spatial resolution of scalp EEG, the organization of cortical neural sources involved in this expiratory load compensation or during response to hypercapnia, especially the interaction between the premotor cortex, the sensorimotor cortical areas and the perisylvian cortex is unknown. | Épilepsie | Non applicable | À vérifier | France | À vérifier |
| Indapamide (T2)The principal scientific objective of the trial is to identify the factors that are associated with differential blood pressure responses between drugs. This may allow investigators to produce new hypotheses on the pathophysiology of hypertension and on the mechanisms of drug action. These factors can be of different types: * Environmental factors (sodium or alcohol intake); * Morphological (height, weight, body mass index, body surface area); * Initial blood pressure; * Electrocardiogram (ECG) parameters of left ventricular hypertrophy; * Biological parameters as the activity level of the renin angiotensin aldosterone system; * Genetic polymorphisms. | Hypertension | Phase 4 | À vérifier | France | À vérifier |
| nomegestrol acetateMultiple sclerosis (MS) affects 1 in 1000 people in western countries, mainly women in their childbearing years. It is an autoimmune disease of the central nervous system (CNS), which results in a chronic focal inflammatory response with subsequent demyelination and axonal loss. Recent prospective studies reported a significant decline by two-thirds in the rate of relapses during the third trimester of pregnancy and a significant increase by two-thirds during the first three months post-partum by comparison to the relapse rate observed during the year prior to the pregnancy (Confavreux et al., 1998). These dramatic changes in the relapse rate occur at a time when the impregnation of many substances (among which, sexual steroids) is at its highest, before a dramatic decline to the pre-pregnancy levels, immediately following delivery. It may be hypothesized that sexual steroids could exert beneficial effects through a modulation of the immune state with a lowering of the pro-inflammatory lymphocyte responses of the Th1 type and an enhancement of the anti-inflammatory responses of the Th2 type. They may also play a direct role in the remyelination of central nervous system lesions, as they do in the peripheral nervous system. The POPART'MUS study is a European, multicentre, randomized, placebo-controlled and double-blind clinical trial, which aims to prevent MS relapses related to the post-partum condition, by administering high doses of progestin (nomegestrol acetate), in combination with endometrial protective doses of estradiol. Treatment will be given immediately after delivery and continuously during the first three months post-partum. Assuming the results of the trial to be positive, this new treatment could be considered in the relapsing-remitting phase of the disease in women afar from pregnancy and post-partum. | SEP | Phase 3 | Remyélinisation | France | À vérifier |
| Perindopril (T1)The principal scientific objective of the trial is to identify the factors that are associated with differential blood pressure responses between drugs. This may allow investigators to produce new hypotheses on the pathophysiology of hypertension and on the mechanisms of drug action. These factors can be of different types: * Environmental factors (sodium or alcohol intake); * Morphological (height, weight, body mass index, body surface area); * Initial blood pressure; * Electrocardiogram (ECG) parameters of left ventricular hypertrophy; * Biological parameters as the activity level of the renin angiotensin aldosterone system; * Genetic polymorphisms. | Hypertension | Phase 4 | À vérifier | France | À vérifier |
| PET/MRI acquisitionDespite the continuous development of new antiseizure medications over the past 25 years, 30% of patients with epilepsy suffer from drug-resistant seizures and are at risk of epilepsy-related complications, like cognitive dysfunctions, sleep-disordered breathing or Sudden and Unexpected Death in Epilepsy (SUDEP). SUDEP typically occurs during sleep, after a nocturnal seizure, and primarily results from a postictal central respiratory dysfunction in patients with generalized convulsive seizure (GCS), suggesting that interaction between respiratory dysfunction and sleep state may play a role in its pathophysiology. Post-mortem data in SUDEP patients showed alteration of neuronal populations involved in respiratory control in the medulla. Accordingly, pharmacologic strategies aimed at reducing the severity of postictal respiratory dysfunction has appeared as one of the most promising way to prevent SUDEP. However, no encouraging result has hitherto been reported. Interconnections between the complex network that regulates arousal and sleep and the respiratory network are numerous. They primarily include the relation between chemosensitive regulation and arousal system to ensure asphyxia-induced arousal (i.e. arousal to elevated CO2), especially through serotonin (5HT)-dependent connections in brain stem. The link between alterations of the brainstem networks involved in arousal regulation and respiratory dysfunction has not been characterized in patients with epilepsy yet. Like 5HT, adenosine is deeply implicated in the regulation of sleep and central respiratory control. Seizures transiently increase adenosine extracellular levels. Adenosine physiological effects in the brain are mediated through the activation of two types of Adenosine receptors (ARs), A1Rs and A2ARs. Extracellular adenosine promotes sleep via A1R-dependant inhibition of glutamatergic neurons in the basal forebrain, but also via A2AR-dependant activation of neurons in the nucleus accumbens. Respiration is also inhibited by A1R and A2AR. Most importantly, it has been shown that drug-resistant epilepsy is associated with long-term alterations of ARs cortical expression. However, whether or not a similar epilepsy-related plasticity of ARs occurs in the brainstem and may participate to chronic arousal and respiratory dysfunction in epilepsy has never been investigated. Considering the tight interplay between central respiratory control, arousal regulation and brainstem adenosine, the main hypothesis of the BRAVE study is that epilepsy might result in alterations of the distribution of A1Rs in the brainstem structures involved in respiratory regulation and/or arousal control, especially in the brainstem structures involved in respiratory regulation under hypercapnic condition. The study combines clinical respiratory characterization, morphological, functional and metabolic imaging, using the hybrid simultaneous 3T MRI-PET scanner (Siemens Biograph mMR) of the CERMEP. Combining PET with anatomical and functional MR imaging enables non-invasively in vivo mapping of receptor binding and functional neuronal assessment of a physiological task in the entire brain with high spatial resolution. Investigators already performed fMRI study of respiratory centers, showing number of functional changes in brainstem regions participating to the central control of respiration, including reduced activation during breath-holding fMRI, in patients with epilepsy. The BRAVE study will use the same respiratory paradigm as the one used in this past study. PET imaging will be focused on A1R, using \[18F\]CPFPX, a selective A1R antagonist. | Épilepsie | Non applicable | À vérifier | France | À vérifier |
| RESPONSE — French Registry for Monitoring Pregnancies for Multiple SclerosisThe influence of pregnancy on the course of multiple sclerosis (MS) has long been a controversial topic. After the publication of the first large prospective study of pregnancy and MS in 1998, counselling of women with MS has radically changed and many patients have been able to fulfill their desire of motherhood. However, there are still some challenges for the neurologist, who has to face old unanswered questions or new issues, regarding the use of disease modifying drugs (DMDs) in this period of life, effects on the short and long term outcome of the mother (in terms of relapses and disability) and the child, role of breast-feeding and locoregional analgesia. To set up a national prospective pregnancy registry for patients with MS, nested within the Observatoire Français de la Sclérose en Plaque (OFSEP) cohort, owing to a better knowledge of interactions between MS and pregnancy-related issues (pregnancy itself, locoregional analgesia, breastfeeding, impact of using or stopping DMDs on women/children…) | SEP | À vérifier | À vérifier | France, Martinique | À vérifier |
| SEEG monitoring30% of patients with epilepsy suffer from drug-resistant seizures and have a greater risk of premature mortality than the general population. Among all causes of death, the most frequent is SUDEP, for sudden and unexpected death in epilepsy patients. SUDEP typically occurs after a nocturnal seizure, and primarily results from a postictal central respiratory dysfunction in patients with generalized convulsive seizure (GCS), suggesting the critical role of seizure-related impairment of breathing control, and underscoring the importance of monitoring and preventive interventions during the post-ictal phase. Most of patients with drug-resistant seizures demonstrate transient peri-ictal apnea and hypoxemia especially in the aftermath of a GCS. Experimental and clinical data suggest that most SUDEP primarily result from a fatal seizure-related respiratory arrest 5. Apnea was the primary cause of death in several epilepsy models. In patients whose SUDEP had occurred during long-term video-EEG monitoring, we observed fatal postictal central apnea after a nocturnal GCS in all SUDEP. Accordingly, it is currently hypothesized that in a subgroup of patients, repetition of seizures may contribute to chronic alteration of respiratory regulation which may increase the risk of fatal postictal central respiratory arrest. Central regulation of autonomic function is ensured by the so-called Central Autonomic Network (CAN), which anatomy in humans has primarily been investigated in neuroimaging studies or using intraEEG (iEEG) data in patients with drug-resistant focal epilepsy undergoing presurgical evaluation with intracerebral electrodes. Central regulation of breathing primarily rely on brainstem, especially the preBötzinger complex for rhythm generation and the retrotrapezoid nucleus and dorsal raphe for chemoreception, especially ventilatory response to hypercapnia. However, through an intricated structures connecting these regions, this respiratory signal projects to a network of cortical and subcortical regions mainly including the limbic and sensorimotor cortical areas. Studies in patients undergoing iEEG reinforced the role of limbic and paralimbic structures, with transient central apnea elicited by direct electrical stimulation of amygdala, hippocampus, anterior parahippocampal, and antero-mesial fusiform gyri. However, our group also reported transient hypoxemia could be elicited by cortical direct electrical stimulation outside the temporo-limbic structures, most commonly after stimulation of the perisylvian cortex. Importantly, our group recently showed that involvement of this perisylvian cortex in the epileptogenic zone is a strong risk factor of SUDEP, reinforcing the importance of further studying its integration in the cortical control of respiration. The involvement of cortical control of ventilation is particularly important to ensure expiratory load compensation, a typical situation after GCS, which is associated with airway obstruction, especially when the face is positioned into the pillow. This cortical component of the physiological response to experimental expiratory loads was investigated in healthy subjects through the study of EEG activity during an expiratory load compensation protocol. Accordingly, EEGs were processed by ensemble averaging expiratory time-locked segments and examined for pre-expiratory EEG potentials, defined as a slow negative shift from the baseline signal preceding expiration, and suggestive of cortical preparation of expiration. Expiratory load compensation was associated with EEG premotor potential presumably involving the supplementary motor area. However, because of the limited spatial resolution of scalp EEG, the organization of cortical neural sources involved in this expiratory load compensation or during response to hypercapnia, especially the interaction between the premotor cortex, the sensorimotor cortical areas and the perisylvian cortex is unknown. | Épilepsie | Non applicable | À vérifier | France | À vérifier |
| Indapamide (T2)The principal scientific objective of the trial is to identify the factors that are associated with differential blood pressure responses between drugs. This may allow investigators to produce new hypotheses on the pathophysiology of hypertension and on the mechanisms of drug action. These factors can be of different types: * Environmental factors (sodium or alcohol intake); * Morphological (height, weight, body mass index, body surface area); * Initial blood pressure; * Electrocardiogram (ECG) parameters of left ventricular hypertrophy; * Biological parameters as the activity level of the renin angiotensin aldosterone system; * Genetic polymorphisms. | Hypertension | Phase 4 | À vérifier | France | À vérifier |
| nomegestrol acetateMultiple sclerosis (MS) affects 1 in 1000 people in western countries, mainly women in their childbearing years. It is an autoimmune disease of the central nervous system (CNS), which results in a chronic focal inflammatory response with subsequent demyelination and axonal loss. Recent prospective studies reported a significant decline by two-thirds in the rate of relapses during the third trimester of pregnancy and a significant increase by two-thirds during the first three months post-partum by comparison to the relapse rate observed during the year prior to the pregnancy (Confavreux et al., 1998). These dramatic changes in the relapse rate occur at a time when the impregnation of many substances (among which, sexual steroids) is at its highest, before a dramatic decline to the pre-pregnancy levels, immediately following delivery. It may be hypothesized that sexual steroids could exert beneficial effects through a modulation of the immune state with a lowering of the pro-inflammatory lymphocyte responses of the Th1 type and an enhancement of the anti-inflammatory responses of the Th2 type. They may also play a direct role in the remyelination of central nervous system lesions, as they do in the peripheral nervous system. The POPART'MUS study is a European, multicentre, randomized, placebo-controlled and double-blind clinical trial, which aims to prevent MS relapses related to the post-partum condition, by administering high doses of progestin (nomegestrol acetate), in combination with endometrial protective doses of estradiol. Treatment will be given immediately after delivery and continuously during the first three months post-partum. Assuming the results of the trial to be positive, this new treatment could be considered in the relapsing-remitting phase of the disease in women afar from pregnancy and post-partum. | SEP | Phase 3 | Remyélinisation | France | À vérifier |
| 1 Hypercapnic challenge while participant is awakeDespite the continuous development of new antiseizure medications over the past 25 years, 30% of patients with epilepsy suffer from drug-resistant seizures and are at risk of epilepsy-related complications, like cognitive dysfunctions, sleep-disordered breathing or Sudden and Unexpected Death in Epilepsy (SUDEP). SUDEP typically occurs during sleep, after a nocturnal seizure, and primarily results from a postictal central respiratory dysfunction in patients with generalized convulsive seizure (GCS), suggesting that interaction between respiratory dysfunction and sleep state may play a role in its pathophysiology. Post-mortem data in SUDEP patients showed alteration of neuronal populations involved in respiratory control in the medulla. Accordingly, pharmacologic strategies aimed at reducing the severity of postictal respiratory dysfunction has appeared as one of the most promising way to prevent SUDEP. However, no encouraging result has hitherto been reported. Interconnections between the complex network that regulates arousal and sleep and the respiratory network are numerous. They primarily include the relation between chemosensitive regulation and arousal system to ensure asphyxia-induced arousal (i.e. arousal to elevated CO2), especially through serotonin (5HT)-dependent connections in brain stem. The link between alterations of the brainstem networks involved in arousal regulation and respiratory dysfunction has not been characterized in patients with epilepsy yet. Like 5HT, adenosine is deeply implicated in the regulation of sleep and central respiratory control. Seizures transiently increase adenosine extracellular levels. Adenosine physiological effects in the brain are mediated through the activation of two types of Adenosine receptors (ARs), A1Rs and A2ARs. Extracellular adenosine promotes sleep via A1R-dependant inhibition of glutamatergic neurons in the basal forebrain, but also via A2AR-dependant activation of neurons in the nucleus accumbens. Respiration is also inhibited by A1R and A2AR. Most importantly, it has been shown that drug-resistant epilepsy is associated with long-term alterations of ARs cortical expression. However, whether or not a similar epilepsy-related plasticity of ARs occurs in the brainstem and may participate to chronic arousal and respiratory dysfunction in epilepsy has never been investigated. Considering the tight interplay between central respiratory control, arousal regulation and brainstem adenosine, the main hypothesis of the BRAVE study is that epilepsy might result in alterations of the distribution of A1Rs in the brainstem structures involved in respiratory regulation and/or arousal control, especially in the brainstem structures involved in respiratory regulation under hypercapnic condition. The study combines clinical respiratory characterization, morphological, functional and metabolic imaging, using the hybrid simultaneous 3T MRI-PET scanner (Siemens Biograph mMR) of the CERMEP. Combining PET with anatomical and functional MR imaging enables non-invasively in vivo mapping of receptor binding and functional neuronal assessment of a physiological task in the entire brain with high spatial resolution. Investigators already performed fMRI study of respiratory centers, showing number of functional changes in brainstem regions participating to the central control of respiration, including reduced activation during breath-holding fMRI, in patients with epilepsy. The BRAVE study will use the same respiratory paradigm as the one used in this past study. PET imaging will be focused on A1R, using \[18F\]CPFPX, a selective A1R antagonist. | Épilepsie | Non applicable | À vérifier | France | À vérifier |
| RESPONSE — French Registry for Monitoring Pregnancies for Multiple SclerosisThe influence of pregnancy on the course of multiple sclerosis (MS) has long been a controversial topic. After the publication of the first large prospective study of pregnancy and MS in 1998, counselling of women with MS has radically changed and many patients have been able to fulfill their desire of motherhood. However, there are still some challenges for the neurologist, who has to face old unanswered questions or new issues, regarding the use of disease modifying drugs (DMDs) in this period of life, effects on the short and long term outcome of the mother (in terms of relapses and disability) and the child, role of breast-feeding and locoregional analgesia. To set up a national prospective pregnancy registry for patients with MS, nested within the Observatoire Français de la Sclérose en Plaque (OFSEP) cohort, owing to a better knowledge of interactions between MS and pregnancy-related issues (pregnancy itself, locoregional analgesia, breastfeeding, impact of using or stopping DMDs on women/children…) | SEP | À vérifier | À vérifier | France, Martinique | À vérifier |
| SEEG monitoring30% of patients with epilepsy suffer from drug-resistant seizures and have a greater risk of premature mortality than the general population. Among all causes of death, the most frequent is SUDEP, for sudden and unexpected death in epilepsy patients. SUDEP typically occurs after a nocturnal seizure, and primarily results from a postictal central respiratory dysfunction in patients with generalized convulsive seizure (GCS), suggesting the critical role of seizure-related impairment of breathing control, and underscoring the importance of monitoring and preventive interventions during the post-ictal phase. Most of patients with drug-resistant seizures demonstrate transient peri-ictal apnea and hypoxemia especially in the aftermath of a GCS. Experimental and clinical data suggest that most SUDEP primarily result from a fatal seizure-related respiratory arrest 5. Apnea was the primary cause of death in several epilepsy models. In patients whose SUDEP had occurred during long-term video-EEG monitoring, we observed fatal postictal central apnea after a nocturnal GCS in all SUDEP. Accordingly, it is currently hypothesized that in a subgroup of patients, repetition of seizures may contribute to chronic alteration of respiratory regulation which may increase the risk of fatal postictal central respiratory arrest. Central regulation of autonomic function is ensured by the so-called Central Autonomic Network (CAN), which anatomy in humans has primarily been investigated in neuroimaging studies or using intraEEG (iEEG) data in patients with drug-resistant focal epilepsy undergoing presurgical evaluation with intracerebral electrodes. Central regulation of breathing primarily rely on brainstem, especially the preBötzinger complex for rhythm generation and the retrotrapezoid nucleus and dorsal raphe for chemoreception, especially ventilatory response to hypercapnia. However, through an intricated structures connecting these regions, this respiratory signal projects to a network of cortical and subcortical regions mainly including the limbic and sensorimotor cortical areas. Studies in patients undergoing iEEG reinforced the role of limbic and paralimbic structures, with transient central apnea elicited by direct electrical stimulation of amygdala, hippocampus, anterior parahippocampal, and antero-mesial fusiform gyri. However, our group also reported transient hypoxemia could be elicited by cortical direct electrical stimulation outside the temporo-limbic structures, most commonly after stimulation of the perisylvian cortex. Importantly, our group recently showed that involvement of this perisylvian cortex in the epileptogenic zone is a strong risk factor of SUDEP, reinforcing the importance of further studying its integration in the cortical control of respiration. The involvement of cortical control of ventilation is particularly important to ensure expiratory load compensation, a typical situation after GCS, which is associated with airway obstruction, especially when the face is positioned into the pillow. This cortical component of the physiological response to experimental expiratory loads was investigated in healthy subjects through the study of EEG activity during an expiratory load compensation protocol. Accordingly, EEGs were processed by ensemble averaging expiratory time-locked segments and examined for pre-expiratory EEG potentials, defined as a slow negative shift from the baseline signal preceding expiration, and suggestive of cortical preparation of expiration. Expiratory load compensation was associated with EEG premotor potential presumably involving the supplementary motor area. However, because of the limited spatial resolution of scalp EEG, the organization of cortical neural sources involved in this expiratory load compensation or during response to hypercapnia, especially the interaction between the premotor cortex, the sensorimotor cortical areas and the perisylvian cortex is unknown. | Épilepsie | Non applicable | À vérifier | France | À vérifier |
| biological samplesSystemic autoimmune diseases associated with type I interferon (IFN-I) dysregulation, such as systemic lupus erythematosus, systemic sclerosis, myositis, and mixed or undifferentiated connective tissue diseases, and genetic type 1 interferonopathies are characterized by chronic and excession IFN-I signaling and production contributing to disease pathogenesis. Aberrant IFN-I production can be triggered through the activation of multiple signaling pathways, particularly those involving intracellular and extracellular RNA and DNA sensing receptors. We hypothesize that excessive IFN-I production results from an increased tonic activation state of nucleic acid sensors and/or an enhanced responsiveness of these sensors to endogenous nucleic acids, thereby sustaining pathological IFN-I signaling and chronic inflammation. The aim of this study is to characterize the type I interferon (IFN-I) response, defined by both the IFN-I gene signature and plasma IFN-α levels, following stimulation with a panel of ligands specific for DNA- and RNA-sensing pathways. | Myopathies | Non applicable | Immunomodulation | France | À vérifier |
Essais cliniques
7| Molécule | Indication / population | Phase | NCT | Titre | Statut |
|---|---|---|---|---|---|
| ULTRAFILTRATION | Insuffisance cardiaque | Non applicable | NCT02846337 | UF-CARE — Ultrafiltration Versus Medical Therapies in the Management of the Cardio Renal Syndrome | COMPLETED |
| biological samples | Myopathies | Non applicable | NCT07837986 | SAFRAN — Investigation of Type I Interferon Excess in Patients With Systemic Autoimmune Diseases and Genetic Type I Interferonopathies | NOT_YET_RECRUITING |
| SEEG monitoring | Épilepsie | Non applicable | NCT07599150 | ICARE — Intracranial CArtography of Cortical Contribution to Respiratory Load Compensation in Epilepsy | RECRUITING |
| RESPONSE — French Registry for Monitoring Pregnancies for Multiple Sclerosis | SEP | À vérifier | NCT03900221 | RESPONSE — French Registry for Monitoring Pregnancies for Multiple Sclerosis | RECRUITING |
| 1 Hypercapnic challenge while participant is awake | Épilepsie | Non applicable | NCT07249034 | BRAVE — Impact of Epilepsy on the Brainstem Adenosine Pathway and Its Relation With Arousal and Respiratory Reactivity | RECRUITING |
| nomegestrol acetate | SEP | Phase 3 | NCT00127075 | POPART'MUS: Prevention of Post Partum Relapses With Progestin and Estradiol in Multiple Sclerosis | UNKNOWN |
| Indapamide (T2) | Hypertension | Phase 4 | NCT00128518 | IDEAL Study: Identification of the Determinants of the Efficacy of Arterial Blood Pressure Lowering Drugs | COMPLETED |
Publications
30| Molécule | Indication / population | Titre | Journal | Date |
|---|---|---|---|---|
| biological samples | Carbon-coated CoNiFeCuCr high-entropy alloy nanoparticles for robust electrochemical simultaneous detection of dopamine and uric acid. | Talanta | ||
| biological samples | DNA- and aptamer-based biosensors for Alzheimer's disease biomarkers toward clinical translation. | Talanta | ||
| biological samples | Immunoaffinity functionalisation of coated blades for fast, specific and sensitive extraction and analysis of veterinary medicine. | Talanta | ||
| Expiratory load compensation | Respiratory physiological reactions during expiratory muscle training in patients with stable severe chronic obstructive pulmonary disease (COPD). | Physiology & behavior | ||
| Expiratory load compensation | Females exhibit greater cardiac volume reductions with expiratory muscle loading during submaximal exercise compared to males. | The Journal of physiology | ||
| Expiratory load compensation | First-Month Adherence to Home Non-Invasive Ventilation in Stable Hypercapnic COPD: Associations with BMI and Bicarbonate Levels. | International journal of chronic obstructive pulmonary disease | ||
| Hypercapnic challenge | Sex differences in cerebrovascular function across an aerobic exercise intervention in older adults using MRI: Results from the Brain in Motion study. | Physiological reports | ||
| Hypercapnic challenge | AAVcc47- Gene Therapy Ameliorates Respiratory Pathology in Mouse Model of Duchenne Muscular Dystrophy. | The Yale journal of biology and medicine | ||
| Hypercapnic challenge | Effect of chronic high-altitude hypoxia on retinal vascular phenotype, choroidal and retinal vasoreactivity in Peruvian highlanders. | Experimental physiology | ||
| SEEG monitoring | Posterior occipitotemporal stereoelectroencephalography implantation in a patient with artificial dural reconstruction: A case report. | Surgical neurology international | ||
| SEEG monitoring | Seizure outcomes of sEEG-guided surgery for temporal vs. extratemporal epilepsy in children. | Epilepsy & behavior : E&B | ||
| SEEG monitoring | The value of fast ripples in identifying extra-temporal epileptogenicity and predicting surgical outcomes in temporal plus epilepsy: A retrospective SEEG cohort study. | Epilepsy research | ||
| Comprehensive respiratory monitoring | Best practices for respiratory function training in perioperative patients with lung cancer: A scoping review and evidence synthesis. | Asia-Pacific journal of oncology nursing | ||
| Comprehensive respiratory monitoring | Acute spinal cord injury-acquired pneumonia induces sustained lung injury in mice. | Experimental neurology | ||
| Comprehensive respiratory monitoring | Effects of MC-100093, GLT-1 enhancer, in mesolimbic brain regions of C57BL/6 mouse exposed to hydrocodone high-dose challenge using comprehensive laboratory monitoring system. | IBRO neuroscience reports | ||
| PET/MRI acquisition | Sequential and Hybrid PET/MRI Acquisition in Follow-Up Examination of Glioblastoma Show Similar Diagnostic Performance. | Cancers | ||
| PET/MRI acquisition | Preoperative 11 C-Methionine PET-MRI in Pediatric Infratentorial Tumors. | Clinical nuclear medicine | ||
| PET/MRI acquisition | Test-retest reproducibility of structural and proxy estimates of brain connectivity at rest. | NeuroImage | ||
| 1 Hypercapnic challenge while participant is awake | Upper airway resistance during progressive hypercapnia and progressive hypoxia in normal awake subjects. | Respiration physiology | ||
| 1 Hypercapnic challenge while participant is awake | Catecholaminergic neurons projecting to the paraventricular nucleus of the hypothalamus are essential for cardiorespiratory adjustments to hypoxia. | American journal of physiology. Regulatory, integrative and comparative physiology | ||
| estradiol | Restoring ovulation in functional hypothalamic amenorrhea: impact of polycystic ovarian morphology on hormonal response to pulsatile GnRH. | Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology | ||
| estradiol | Transdermal versus oral hormone replacement therapy and bone mass density in Turner syndrome patients: a pilot study. | Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology | ||
| estradiol | Optimizing estradiol serum levels for optimal skeletal and cardiovascular health during transdermal menopausal hormone therapy. | Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology | ||
| nomegestrol acetate | Retraction notice to "The use of oral nomegestrol acetate/estradiol in rapid and random start preparation of endometrium before office hysteroscopic polypectomies: A multicenter, prospective, randomized controlled trial" [Eur. J. Obstet. Gynecol. Reprod. Biol. 299 (2024) 213-218]. | European journal of obstetrics, gynecology, and reproductive biology | ||
| estradiol | Hepatic SIRT6 Deficiency Accelerates Female-Specific Aging Through SULT1E1-Mediated Estrogen Depletion. | International journal of molecular sciences | ||
| estradiol | Cadmium Toxicity in Testis Organoids: Validation of an In Vitro Model for Testicular Toxicology. | Toxicologic pathology | ||
| nomegestrol acetate | A detailed review of pharmacokinetics/pharmacodynamics of progestogens in oral contraception. | Frontiers in endocrinology | ||
| nomegestrol acetate | Progestin therapy in premenopausal women with incidental meningioma-a narrative review and recommendations for women's health specialists. | Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology | ||
| Perindopril (T1) | Takotsubo syndrome in a cancer patient treated with a combination of anti-cancer drugs including immune checkpoint inhibitors: a case report. | European heart journal. Case reports | ||
| Perindopril (T1) | Hypertension and myocardial fibrosis: A systematic review and meta-analysis. | Clinical radiology |