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

Diabetes Mellitus, Type 2 Clinical Trial

— GLP1R-T2D  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04733508
• Other study ID #: NL63933.091.17
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2019
• Est. completion date: December 1, 2022

Study information

• Verified date: October 2020
• Source: Radboud University
• Contact: Sanne van Lith, PhD
• Phone: 0031243613813
• Email: sanne.vanlith[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: December 1, 2022
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• 111In-DTPA-exendin-4
Injection of 111In-DTPA-exendin-4 and localization of the tracer in excised pancreatic tissue using autoradiography
• IRDye800CW-exendin-4
Injection of IRDye800CW-exendin-4 and localization of the tracer in excised pancreatic tissue using fluorescence microscopy

Locations

Country	Name	City	State
Netherlands	Radboud University Medical Center	Nijmegen	Gelderland

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	University of Coimbra

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pancreatic exendin uptake 111In-DTPA exendin-4	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
Primary	Pancreatic exendin uptake 111In-DTPA exendin-4	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
Primary	Beta cell function	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
Primary	Blood glucose levels	Glycemic control will be determined by monitoring blood glucose levels	Blood glucose levels will be continuously monitored a week prior to surgery
Primary	HbA1C levels	HbA1C levels will be determined as a measure of glycemic control	HbA1C levels will be determined within a week before planned surgery
Primary	Pancreatic exendin uptake IRDye800CW-exendin-4	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
Primary	Gene expression	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