Clinical trial NCT04615910: A GLP-1 Receptor PET Imaging Substudy Within the VER-A-T1D Trial Investigating the Effects on Beta Cell Mass
Official title: A GLP-1 Receptor PET Imaging Substudy Within the VER-A-T1D Trial Investigating the Effects on Beta Cell Mass
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diabetes Mellitus
Keywords: Verapamil
Type 1 Diabetes Mellitus
exendin
Beta cell mass
PET imaging
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Assistance Publique - Hôpitaux de Paris
name: Medical University of Vienna
name: Bart's London
name: KU Leuven
First posted: 2020-11-04
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Type 1 Diabetes Mellitus
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of the trial is to measure pancreatic uptake of 68Ga-NODAGA-exendin by PET/CT for detection of intra-individual differences in beta cell mass before and after treatment with Verapamil.

Detailed description: The VER-A-T1D (Verapamil SR in adults with Type 1 Diabetes) study is an intervention study within the INNODIA project (an Innovative Medicines Initiative consortium (IMI-2), established through Horizon 2020 initiative of the European Union, involving academic, industry and charitable partners).

In the VER-A-T1D study, the effects of treatment of newly diagnosed patients with T1D with Verapamil will be evaluated. Verapamil appears to protect beta cell function, an effect that could in part be caused by protection against beta cell apoptosis. GLP-1 receptors are expressed in high densities in beta cells. Exendin, a GLP-1 receptor agonist, can be labeled with radionuclides and thus be utilized for visualization of beta cells in vivo by positron emission tomography (PET). This technology has been demonstrated to deliver quantitative information of the radiotracer uptake in the pancreas demonstrating a linear correlation with beta cell mass. In VER-A-T1D, we propose to measure beta cell mass at the time points of inclusion and at evaluation after 12 months. If verapamil protects beta cells against apoptosis, we expect that the uptake of the radiotracer will be higher at 12 months in comparison to the first measurement in the treatment group. The study will be a substudy to VER-A-T1D.

Eligibility criteria: Inclusion Criteria:

* • Have given written informed consent
* • Age ≥18 and \<45 at consent
* • Must have a diagnosis of T1D of within 6 weeks duration at screening (date of the first insulin
* injection)
* • Must have at least one or more diabetes-related autoantibodies present at screening
* • Must have random C-peptide levels ≥200 pmol/L measured at screening
* • Be willing to comply with intensive diabetes management

Exclusion Criteria:

* Treatment with synthetic Exendin (Exenatide, Byetta®) or Dipeptidyl-Peptidase IV inhibitors (to exclude interferences with imaging, specifically mentioned although in principle part of exclusion criteria of VER-A-T1D)
* Renal disease defined as MDRD \<40 ml/min/1.73 m2
* Pregnancy or the wish to become pregnant within 2 months after the second PET/CT scan.

Primary outcomes:
measure: Pancreatic 68Ga-exendin uptake
timeFrame: Change from time of inclusion to 12 months into treatment
Secondary outcomes:
measure: Correlation of 68Ga-exendin uptake and C-peptide
timeFrame: 12 months into treatment
measure: relative 68Ga-exendin uptake
timeFrame: 12 months into treatment
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: University of Vienna
city: Paris
country: France
facility: Assistance Publique hopitaux de Paris
Study officials:
References: