A GLP-1 Receptor PET Imaging Substudy Within the VER-A-T1D Trial Investigating the Effects on Beta Cell Mass (Ver-A-image)

Radboud University Medical Center

Status and phase: Enrolling; Phase 2

Conditions: Diabetes Mellitus

Treatments: Radiation: 68Ga-NODAGA-exendin-4 PET/CT

Study type: Interventional

Funder types: Other

Identifiers

NCT04615910

20201013

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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30 participants in 2 patient groups, including a placebo group

Verapamil

Experimental group

Description:

Patients treated with Verapamil within the Ver-A-T1D trial

Treatment:

Radiation: 68Ga-NODAGA-exendin-4 PET/CT

Placebo

Placebo Comparator group

Description:

Patients treated with placebo within the Ver-A-T1D trial

Treatment:

Radiation: 68Ga-NODAGA-exendin-4 PET/CT