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

January 28, 2021 updated by: Radboud University Medical Center

Glucagon Like Peptide 1 Receptor (GLP1R) Expression and Beta-cell Mass in Patients With Type 2 Diabetes - the Role of Glucose Homeostasis on Uptake of Beta-cell Tracer Exendin-4

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

28

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 111In-exendin-DTPA
Injection of 111In-exendin-DTPA for subsequent localization of the tracer in excised tissue using autoradiography
Drug: 111In-DTPA-exendin-4
Injection of 111In-DTPA-exendin-4 and localization of the tracer in excised pancreatic tissue using autoradiography
Experimental: exendin-IRDye800CW
Injection of exendin-4-IRDye800CW for subsequent localization of the tracer in excised tissue using fluorescence microscopy
Drug: IRDye800CW-exendin-4
Injection of IRDye800CW-exendin-4 and localization of the tracer in excised pancreatic tissue using fluorescence microscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pancreatic exendin uptake 111In-DTPA exendin-4
Time Frame: 111In-DTPA-exendin-4 injection will be performed a day before planned surgery, and uptake will be determined using ex vivo SPECTof the resected tissue one day after surgery
The pancreatic uptake of 111In-DTPA-exendin-4 will be quantified using ex vivo SPECT
111In-DTPA-exendin-4 injection will be performed a day before planned surgery, and uptake will be determined using ex vivo SPECTof the resected tissue one day after surgery
Pancreatic exendin uptake 111In-DTPA exendin-4
Time Frame: 111In-DTPA-exendin-4 injection will be performed a day before planned surgery, and uptake will be determined with tissue autoradiography immediately after resection
The pancreatic uptake of 111In-DTPA-exendin-4 will be quantified using tissue autoradiography
111In-DTPA-exendin-4 injection will be performed a day before planned surgery, and uptake will be determined with tissue autoradiography immediately after resection
Beta cell function
Time Frame: The glucose tolerance test will be performed within a week before planned surgery
The beta cell function will be determined with a glucose tolerance test
The glucose tolerance test will be performed within a week before planned surgery
Blood glucose levels
Time Frame: Blood glucose levels will be continuously monitored a week prior to surgery
Glycemic control will be determined by monitoring blood glucose levels
Blood glucose levels will be continuously monitored a week prior to surgery
HbA1C levels
Time Frame: HbA1C levels will be determined within a week before planned surgery
HbA1C levels will be determined as a measure of glycemic control
HbA1C levels will be determined within a week before planned surgery
Pancreatic exendin uptake IRDye800CW-exendin-4
Time Frame: IRDye800CW-exendin-4 injection will be performed a day before planned surgery, and uptake will be determined using microscopy in the excised tissue
Uptake of IRDye800CW-exendin4 will be visualized with microscopy
IRDye800CW-exendin-4 injection will be performed a day before planned surgery, and uptake will be determined using microscopy in the excised tissue
Gene expression
Time Frame: Gene expression will be determined in the excised pancreatic tissue immediately after resection
Gene expression levels will be determined with quantitative polymerase chain reaction (qPCR)
Gene expression will be determined in the excised pancreatic tissue immediately after resection

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

University of Coimbra

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2019

Primary Completion (Anticipated)

June 1, 2022

Study Completion (Anticipated)

December 1, 2022

Study Registration Dates

First Submitted

October 8, 2020

First Submitted That Met QC Criteria

January 28, 2021

First Posted (Actual)

February 2, 2021

Study Record Updates

Last Update Posted (Actual)

February 2, 2021

Last Update Submitted That Met QC Criteria

January 28, 2021

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL63933.091.17

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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