Diabetes MellitusGLP1R-T2DNCT04733508
Glucagon Like Peptide 1 Receptor (GLP1R) Expression and Beta-cell Mass in Patients With Type 2 Diabetes
A study testing 111In-DTPA-exendin-4 and IRDye800CW-exendin-4 in people with Diabetes Mellitus and Diabetes Mellitus, Type 2, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Validation of the exendin-based beta cell imaging technique in patients with type 2 diabetes Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Mellitus, Diabetes Mellitus, Type 2
- What is being tested?
- 111In-DTPA-exendin-4 and IRDye800CW-exendin-4
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Nov 2019to 1 Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Scheduled for partial or complete pancreatectomy at Radboudumc
Who cannot join
- 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 locations and contacts
1 site in 1 country.
Martin Gotthardt, MD, prof contact
Netherlands1 site, 1 recruiting
- Recruiting
Radboud University Medical Center
Nijmegen, Gelderland, 6525 GA
Sanne van Lith, PhD, 0031243613813, sanne.vanlith@radboudumc.nl
Martin Gotthardt, MD, Prof, Martin.Gotthardt@radboudumc.nl
About this study
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
Validation of the exendin-based beta cell imaging technique in patients with type 2 diabetes
Read the 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.
- Conditions
- Diabetes Mellitus, Diabetes Mellitus, Type 2
- Being tested
- 111In-DTPA-exendin-4, IRDye800CW-exendin-4
- Keywords
- nuclear imaging, beta cell mass, exendin-4
- Medical subject headings
- Diabetes Mellitus, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
111In-DTPA-exendin-4Drug
Injection of 111In-DTPA-exendin-4 and localization of the tracer in excised pancreatic tissue using autoradiography
IRDye800CW-exendin-4Drug
Injection of IRDye800CW-exendin-4 and localization of the tracer in excised pancreatic tissue using fluorescence microscopy
| Study group | Role | What they receive |
|---|---|---|
| 111In-exendin-DTPA | Experimental | Injection of 111In-exendin-DTPA for subsequent localization of the tracer in excised tissue using autoradiography Receives: Drug: 111In-DTPA-exendin-4 |
| exendin-IRDye800CW | Experimental | Injection of exendin-4-IRDye800CW for subsequent localization of the tracer in excised tissue using fluorescence microscopy Receives: Drug: IRDye800CW-exendin-4 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pancreatic exendin uptake 111In-DTPA exendin-4
The pancreatic uptake of 111In-DTPA-exendin-4 will be quantified using ex vivo SPECT
Measured: 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
The pancreatic uptake of 111In-DTPA-exendin-4 will be quantified using tissue autoradiography
Measured: 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
The beta cell function will be determined with a glucose tolerance test
Measured: The glucose tolerance test will be performed within a week before planned surgery
Blood glucose levels
Glycemic control will be determined by monitoring blood glucose levels
Measured: Blood glucose levels will be continuously monitored a week prior to surgery
HbA1C levels
HbA1C levels will be determined as a measure of glycemic control
Measured: HbA1C levels will be determined within a week before planned surgery
Pancreatic exendin uptake IRDye800CW-exendin-4
Uptake of IRDye800CW-exendin4 will be visualized with microscopy
Measured: 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
Gene expression levels will be determined with quantitative polymerase chain reaction (qPCR)
Measured: Gene expression will be determined in the excised pancreatic tissue immediately after resection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2021
- Study start1 Nov 2019
- Primary completion1 Jun 2022 (estimated)
- Study completion1 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Coimbra
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04733508
- Sponsor's protocol ID
- NL63933.091.17
- Acronym
- GLP1R-T2D
- Status last verified
- Oct 2020
- First submitted
- 8 Oct 2020
- Last updated
- 2 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Jansen TJP, Tokgoz S, Buitinga M, van Lith SAM, Joosten L, Frielink C, Smeets EMM, Stommel MWJ, van der Kolk MB, de Galan BE, Brom M, Boss M, Gotthardt M. Validation of radiolabelled exendin for beta cell imaging by ex vivo autoradiography and immunohistochemistry of human pancreas. EJNMMI Res. 2024 Oct 15;14(1):96. doi: 10.1186/s13550-024-01159-6.
PubMed 39405026
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04733508
- Acronym / sponsor ID
- GLP1R-T2D / NL63933.091.17
- Conditions
- Diabetes Mellitus, Diabetes Mellitus, Type 2
- Keywords
- nuclear imaging, beta cell mass, exendin-4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- University of Coimbra
- Study start
- 1 Nov 2019 (actual)
- Primary completion
- 1 Jun 2022 (estimated)
- Study completion
- 1 Dec 2022 (estimated)
- First posted
- 2 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 111In-exendin-DTPA | Experimental | Drug: 111In-DTPA-exendin-4Injection of 111In-exendin-DTPA for subsequent localization of the tracer in excised tissue using autoradiography |
| exendin-IRDye800CW | Experimental | Drug: IRDye800CW-exendin-4Injection of exendin-4-IRDye800CW for subsequent localization of the tracer in excised tissue using fluorescence microscopy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Scheduled for partial or complete pancreatectomy at Radboudumc
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 111In-DTPA-exendin-4Injection of 111In-DTPA-exendin-4 and localization of the tracer in excised pancreatic tissue using autoradiography | Drug | 111In-exendin-DTPA |
| IRDye800CW-exendin-4Injection of IRDye800CW-exendin-4 and localization of the tracer in excised pancreatic tissue using fluorescence microscopy | Drug | exendin-IRDye800CW |
Primary outcome
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
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
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
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
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
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
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)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2021.
- Derived from this study: PubMed 39405026Jansen TJP, Tokgoz S, Buitinga M, van Lith SAM, Joosten L, Frielink C, Smeets EMM, Stommel MWJ, van der Kolk MB, de Galan BE, Brom M, Boss M, Gotthardt M. Validation of radiolabelled exendin for beta cell imaging by ex vivo autoradiography and immunohistochemistry of human pancreas. EJNMMI Res. 2024 Oct 15;14(1):96. doi: 10.1186/s13550-024-01159-6.
- Individual participant dataSharing planned: Undecided
Related trials for Diabetes Mellitus
Recruiting
Using Ultromics EchoGo HFpEF Algorithm to Identify and Treat High Heart Failure Risk in Patients With Type 2 Diabetes
Heart Failure, Diabetes
Not yet recruiting
STRONG: SMART Trial
Gestational Diabetes Mellitus (GDM)
Recruiting
Continuous Glucose Monitoring Systems in People With Type 2 Diabetes Not Treated With Insulin
Type 2 Diabetes
Active, not recruitingPhase 4
Pentoxifylline in Diabetic Kidney Disease
Diabetic Kidney Disease
Not yet recruiting
Inter-Arm Differences in Continuous Glucose Monitor Readings in Adults With Diabetes
Continuous Glucose Monitoring, Type 1 Diabetes
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Gotthardt, MD, prof contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 111In-DTPA-exendin-4 and IRDye800CW-exendin-4 in people with Diabetes Mellitus and Diabetes Mellitus, Type 2, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sanne van Lith, PhD (0031243613813, sanne.vanlith@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04733508, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2021.