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

Study Overview
=================
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.

Official Title
-----------------
A GLP-1 Receptor PET Imaging Substudy Within the VER-A-T1D Trial Investigating the Effects on Beta Cell Mass

Conditions
-----------------
Diabetes Mellitus

Intervention / Treatment
-----------------
* Radiation: 68Ga-NODAGA-exendin-4 PET/CT


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Type 1 Diabetes Mellitus
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Verapamil<br>Patients treated with Verapamil within the Ver-A-T1D trial | Radiation: 68Ga-NODAGA-exendin-4 PET/CT<br>* 68Ga-NODAGA-exendin-4 PET/CT<br>|
| Placebo Comparator: Placebo<br>Patients treated with placebo within the Ver-A-T1D trial | Radiation: 68Ga-NODAGA-exendin-4 PET/CT<br>* 68Ga-NODAGA-exendin-4 PET/CT<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pancreatic 68Ga-exendin uptake | the total pancreatic uptake of 68Ga-NODAGA-exendin by PET/CT for determination of beta cell mass | Change from time of inclusion to 12 months into treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of 68Ga-exendin uptake and C-peptide | • Changes in 68Ga-NODAGA-exendin pancreas uptake in realtion to changes in C-peptide measurements. | 12 months into treatment | 
| relative 68Ga-exendin uptake | • Differences in 68Ga-NODAGA-exendin uptake between individuals and between the two timepoints of imaging intra-individually | 12 months into treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Verapamil, Type 1 Diabetes Mellitus, exendin, Beta cell mass, PET imaging