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

Phase 2
Recruiting
Conditions
Diabetes Mellitus
Interventions
Radiation: 68Ga-NODAGA-exendin-4 PET/CT
Registration Number
NCT04615910
Lead Sponsor
Radboud University Medical Center
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
30
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
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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo68Ga-NODAGA-exendin-4 PET/CTPatients treated with placebo within the Ver-A-T1D trial
Verapamil68Ga-NODAGA-exendin-4 PET/CTPatients treated with Verapamil within the Ver-A-T1D trial
Primary Outcome Measures
NameTimeMethod
Pancreatic 68Ga-exendin uptakeChange from time of inclusion to 12 months into treatment

the total pancreatic uptake of 68Ga-NODAGA-exendin by PET/CT for determination of beta cell mass

Secondary Outcome Measures
NameTimeMethod
relative 68Ga-exendin uptake12 months into treatment

• Differences in 68Ga-NODAGA-exendin uptake between individuals and between the two timepoints of imaging intra-individually

Correlation of 68Ga-exendin uptake and C-peptide12 months into treatment

• Changes in 68Ga-NODAGA-exendin pancreas uptake in realtion to changes in C-peptide measurements.

Trial Locations

Locations (2)

University of Vienna

🇦🇹

Vienna, Austria

Assistance Publique hopitaux de Paris

🇫🇷

Paris, France

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