Diabetes Mellitus, Diabetes Mellitus, Type 2
Conditions
Keywords
nuclear imaging, beta cell mass, exendin-4
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.
Interventions
DRUG111In-DTPA-exendin-4
Injection of 111In-DTPA-exendin-4 and localization of the tracer in excised pancreatic tissue using autoradiography
DRUGIRDye800CW-exendin-4
Injection of IRDye800CW-exendin-4 and localization of the tracer in excised pancreatic tissue using fluorescence microscopy
Sponsors
University of Coimbra
Radboud University Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Beta cell function | 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 |
| Blood glucose levels | Blood glucose levels will be continuously monitored a week prior to surgery | Glycemic control will be determined by monitoring blood glucose levels |
| Pancreatic exendin uptake 111In-DTPA exendin-4 | 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 |
| HbA1C levels | HbA1C levels will be determined within a week before planned surgery | HbA1C levels will be determined as a measure of glycemic control |
| Pancreatic exendin uptake IRDye800CW-exendin-4 | 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 |
| Gene expression | 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) |
Countries
Netherlands
Contacts
Primary ContactSanne van Lith, PhD
Backup ContactMartin Gotthardt, MD, prof
Outcome results
None listed