Glucagon Like Peptide 1 Receptor (GLP1R) Expression and Beta-cell Mass in Patients With Type 2 Diabetes (GLP1R-T2D)

Radboud University Medical Center

Status: Unknown

Conditions: Diabetes Mellitus; Diabetes Mellitus, Type 2

Treatments: Drug: IRDye800CW-exendin-4; Drug: 111In-DTPA-exendin-4

Study type: Interventional

Funder types: Other

Identifiers

NCT04733508

NL63933.091.17

Details and patient eligibility

About

Validation of the exendin-based beta cell imaging technique in patients with type 2 diabetes

Full description

Rationale: Reliable imaging biomarkers for non-invasive characterisation of beta-cell mass (BCM) are needed to aid understanding regarding the relationship between beta-cell mass and function during the course of type 2 diabetes (T2D). This study will provide critical information necessary to validate the applicability of exendin-based imaging techniques in patients with T2D. The characterization of beta-cells is currently limited to pancreatic specimens available at autopsy, as in vivo pancreatic biopsy is associated with complications unacceptable in clinical studies. To date, only measurements of circulating C-peptide and insulin levels can be obtained, but these measures do not reflect beta-cell mass, only total beta-cell function. Reliable imaging biomarkers for non-invasive characterisation of beta cell mass are therefore needed. These biomarkers could also be used to validate novel therapeutic strategies aimed to increase or preserve BCM or identify whether patients are eligible for a certain therapeutic strategy (e.g. when certain amount of beta-cells is required). One can also think of identifying early responders to therapies, to avoid unnecessary drug use and the accompanying costs.

The objective of this study is to determine the specificity of Exendin-4 during the course of T2D and to examine the role of glycemic control on the correlation between pancreatic Exendin-4 uptake, BCM and GLP-1R expression in patients with T2D undergoing (partial) pancreatectomy. This will allow examination of the role of glycemic control on exendin uptake in humans, but also implementation of clinical guidelines for the interpretation of clinical exendin-based scans in patients with T2D to avoid false interpretation of the scans.

Enrollment: 28 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Scheduled for partial or complete pancreatectomy at Radboudumc

Exclusion criteria

• Previous treatment with synthetic exendin or dipeptidyl-peptidase IV inhibitors within the past 3 months
• Breast feeding
• Pregnancy or the wist to become pregnant within 6 months
• Creatinine clearance below 40ml/min
• Liver disease defined as aspartate aminotransferase of alanine aminotransferase level of more than three times the upper limit of normal range

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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28 participants in 2 patient groups

111In-exendin-DTPA

Experimental group

Description:

Injection of 111In-exendin-DTPA for subsequent localization of the tracer in excised tissue using autoradiography

Treatment:

Drug: 111In-DTPA-exendin-4

exendin-IRDye800CW

Experimental group

Description:

Injection of exendin-4-IRDye800CW for subsequent localization of the tracer in excised tissue using fluorescence microscopy

Treatment:

Drug: IRDye800CW-exendin-4