University Medical Center Groningen — Biomedical Watch V2

Traitements4programmes

Essais2liés

Publications5liées

SourceDBlocale

Traitements

4

Molécule	Indication / population	Phase	Objectif	Pays	Résultat
[18F]MC225P-glycoprotein, an efflux transporter at the blood-brain barrier plays an important role in de development of neurodegenerative disease. A novel PET tracer (\[18F\]MC225) was developed to measure the function of P-glycoprotein and was tested with succes in healthy volunteers. This study aims to evaluate \[18F\]MC225 in neurodegenerative disease.	Alzheimer, Parkinson	Phase 1	À vérifier	Netherlands	À vérifier
Dapagliflozin 10 mg/day (oral)Rationale: Sodium glucose co transporter 2 (SGLT2) inhibitors are a relatively new class of agents, originally developed as oral antihyperglycemic drugs. SGLT2 inhibitors are clinically available since 2012 for the treatment of patients with diabetes mellitus type 2. Later, SGLT2 inhibitors appeared to have also specific reno- and cardioprotective effects. Remarkably, the trials that have been performed thus far excluded patients with an eGFR below 25 mL/min/1.73m2 at inclusion, prevalent dialysis patients, and kidney transplant recipients. This is unfortunate, because especially these patients are at high risk of reaching kidney failure requiring dialysis, cardiovascular complications and mortality, whereas there are only few proven effective therapies. There is emerging evidence from experimental studies and post hoc-analyses of randomized clinical trials that SGLT2 inhibitors may also be effective in preventing cardiovascular and mortality outcomes in these patients with severe CKD, including patients receiving dialysis or living with a kidney transplant. For instance, subgroup analysis of the DAPA-CKD trial comparing 624 patients with an eGFR\<30 to the remainder of the trial population with better kidney function, demonstrated that the efficacy of the SGLT2 inhibitor dapagliflozin in reducing cardiovascular, heart failure and renal outcomes persisted in the population with impaired kidney function. Furthermore, in the DAPA-CKD trial patients continued to use dapagliflozin or placebo when dialysis was initiated. In the subgroup of patients who initiated dialysis, dapagliflozin was associated with a relative risk reduction for mortality of 21%. Finally, in kidney transplant recipients, SGLT2 inhibitors have been shown to be effective in lowering HbA1c, body weight, blood pressure and stabilize kidney function, and these agents were well tolerated and safe. Taken these findings together there is a sound rationale to study the long-term reno- and cardioprotective efficacy and safety of SGLT2 inhibitors in patients with severe CKD. There are two cardiac sub-studies: the cardiac magnetic resonance imaging (MRI) sub-study and the echocardiography sub-study. The echocardiography sub-study is referred to as the "SGLT-2-inhibitors to Target Heart Failure in Peritoneal Dialysis" (STOP-HF-in-PD) study.	Maladie rénale chronique	Phase 3	À vérifier	Australia, Belgium, Germany, Netherlands, Singapore, Spain	À vérifier
[18F]MC225P-glycoprotein, an efflux transporter at the blood-brain barrier plays an important role in de development of neurodegenerative disease. A novel PET tracer (\[18F\]MC225) was developed to measure the function of P-glycoprotein and was tested with succes in healthy volunteers. This study aims to evaluate \[18F\]MC225 in neurodegenerative disease.	Alzheimer	Phase 1	À vérifier	Netherlands	À vérifier
Dapagliflozin 10 mg/day (oral)Rationale: Sodium glucose co transporter 2 (SGLT2) inhibitors are a relatively new class of agents, originally developed as oral antihyperglycemic drugs. SGLT2 inhibitors are clinically available since 2012 for the treatment of patients with diabetes mellitus type 2. Later, SGLT2 inhibitors appeared to have also specific reno- and cardioprotective effects. Remarkably, the trials that have been performed thus far excluded patients with an eGFR below 25 mL/min/1.73m2 at inclusion, prevalent dialysis patients, and kidney transplant recipients. This is unfortunate, because especially these patients are at high risk of reaching kidney failure requiring dialysis, cardiovascular complications and mortality, whereas there are only few proven effective therapies. There is emerging evidence from experimental studies and post hoc-analyses of randomized clinical trials that SGLT2 inhibitors may also be effective in preventing cardiovascular and mortality outcomes in these patients with severe CKD, including patients receiving dialysis or living with a kidney transplant. For instance, subgroup analysis of the DAPA-CKD trial comparing 624 patients with an eGFR\<30 to the remainder of the trial population with better kidney function, demonstrated that the efficacy of the SGLT2 inhibitor dapagliflozin in reducing cardiovascular, heart failure and renal outcomes persisted in the population with impaired kidney function. Furthermore, in the DAPA-CKD trial patients continued to use dapagliflozin or placebo when dialysis was initiated. In the subgroup of patients who initiated dialysis, dapagliflozin was associated with a relative risk reduction for mortality of 21%. Finally, in kidney transplant recipients, SGLT2 inhibitors have been shown to be effective in lowering HbA1c, body weight, blood pressure and stabilize kidney function, and these agents were well tolerated and safe. Taken these findings together there is a sound rationale to study the long-term reno- and cardioprotective efficacy and safety of SGLT2 inhibitors in patients with severe CKD. There are two cardiac sub-studies: the cardiac magnetic resonance imaging (MRI) sub-study and the echocardiography sub-study. The echocardiography sub-study is referred to as the "SGLT-2-inhibitors to Target Heart Failure in Peritoneal Dialysis" (STOP-HF-in-PD) study.	Maladie rénale chronique	Phase 3	À vérifier	Australia, Belgium, Germany, Netherlands, Singapore, Spain	À vérifier

Essais cliniques

2

Molécule	Indication / population	Phase	NCT	Titre	Statut
Dapagliflozin 10 mg/day (oral)	Maladie rénale chronique	Phase 3	NCT05374291	The RENAL LIFECYCLE Trial: A RCT to Assess the Effect of Dapagliflozin on Renal and Cardiovascular Outcomes in Patients With Severe CKD	ACTIVE_NOT_RECRUITING
[18F]MC225	Alzheimer	Phase 1	NCT05853471	[18F]MC225-PET in Neurodegenerative Disease	UNKNOWN

Publications

5

Molécule	Indication / population	Titre	Journal	Date
Dapagliflozin 10 mg/day (oral)		Partial restoration of counterregulatory circulating glucagon by dapagliflozin and low-dose glibenclamide in men with type 1 diabetes: in vitro studies and randomised clinical crossover trial.	EBioMedicine
Dapagliflozin 10 mg/day (oral)		Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial.	Lancet (London, England)
Dapagliflozin 10 mg/day (oral)		Effects of dapagliflozin on proteinuria, glycemic control, and treatment burden in diabetic kidney transplant recipients: a matched cohort study.	Acta diabetologica
[18F]MC225		P-glycoprotein Function in the Rodent Brain Displays a Daily Rhythm, a Quantitative In Vivo PET Study.	The AAPS journal
[18F]MC225		assessment of cardiac P-glycoprotein function with [F]MC225 by using µ-engineered heart tissues.	European heart journal open