Clinical trial NCT04733508: Glucagon Like Peptide 1 Receptor (GLP1R) Expression and Beta-cell Mass in Patients With Type 2 Diabetes
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Diabetes Mellitus
Diabetes Mellitus, Type 2
Keywords: nuclear imaging
beta cell mass
exendin-4
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: University of Coimbra
First posted: 2021-02-02
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pancreatic exendin uptake 111In-DTPA exendin-4
timeFrame: 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
measure: Pancreatic exendin uptake 111In-DTPA exendin-4
timeFrame: 111In-DTPA-exendin-4 injection will be performed a day before planned surgery, and uptake will be determined with tissue autoradiography immediately after resection
measure: Beta cell function
timeFrame: The glucose tolerance test will be performed within a week before planned surgery
measure: Blood glucose levels
timeFrame: Blood glucose levels will be continuously monitored a week prior to surgery
measure: HbA1C levels
timeFrame: HbA1C levels will be determined within a week before planned surgery
measure: Pancreatic exendin uptake IRDye800CW-exendin-4
timeFrame: IRDye800CW-exendin-4 injection will be performed a day before planned surgery, and uptake will be determined using microscopy in the excised tissue
measure: Gene expression
timeFrame: Gene expression will be determined in the excised pancreatic tissue immediately after resection
Secondary outcomes:
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
Study officials:
References: