- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03768518
GLP-1 Receptor Expression in CHI (GLP-1-CHI)
The Physiology of Glucagon-like-peptide-1 Espression in Patients With Endogenous Hyperinsulinism: Correlation With Histopathology
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Congenital hyperinsulinism (CHI) is a rare disease of infants characterized by the presence of functionally defective non-neoplastic beta-cells with inappropriate (over-) secretion of insulin, leading to life-threatening hypoglycaemia. Beta cells specifically express the glucagon-like-peptide-1 (GLP-1R), which could be a promising target for diagnostic and therapeutic purposes. In this study we propose to investigate the physiology of GLP-1 receptor expression in CHI. Expression of the GLP-1 receptor will be quantified in vivo by 68Ga-NODAGA-exendin-4 PET/CT. This data will be compared with post-surgical autoradiography and morphometric determinations.
Furthermore, we will evaluate 68Ga-exendin-4 PET/CT for the pre-operative localization of foci of over-secreting beta cells in CHI and the discrimination between focal and diffuse CHI. We will compare GLP-1R PET/CT to the currently used pre-operative imaging technique (18F-DOPA PET combined with contrast enhanced CT). To compare these imaging techniques according to sensitivity, we will analyze intra-operative findings and clinical outcomes.
These highly relevant data will allow us to evaluate the expression of GLP-1R in CHI and its usefulness as a target for diagnosis of this disease. Since the localization of foci in CHI and the discrimination between focal and diffuse CHI is challenging, surgical removal of unnecessary large portions of the pancreas in frequently necessary. Evaluation of a better target for pre-operative imaging would therefore be of great value.
Objective:
The primary objective is the in vivo and ex vivo investigation of the expression and distribution of the GLP-1R in the pancreas of CHI patients. A 68Ga-NODAGA-exendin 4 PET/CT will be performed in all patients included in this study. The results of quantitative imaging will then be compared to GLP-1R expression and autoradiography of surgical specimens to determine the interdependency of radiotracer uptake, beta cell mass and GLP-1R expression.
Furthermore, GLP-1R imaging will be compared to the standard imaging techniques now used in pre-operative imaging of children with CHI. All patients will undergo the standard imaging procedure, consisting of an 18F-DOPA PET scan combined with a contrast-enhanced CT. The results of the GLP-1R imaging will be compared to standard imaging in respect to sensitivity for localization of the lesion and discrimination between focal and diffuse CHI. This will be determined by the comparison of the results of pre-operative imaging with intra-operative findings.
Also, the safety (side-effects) of 68Ga-NODAGA-exendin and 18F-DOPA will be assessed.
Furthermore, dosimetric calculations will be performed and the minimum radioactivity dose of 68Ga-NODAGA-exendin 4 to obtain acceptable/reliable images will be determined.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Marti Boss
- Phone Number: +31243667243
- Email: marti.boss@radboudumc.nl
Study Locations
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-
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Nijmegen, Netherlands, 6500HB
- Recruiting
- Radboudumc
-
Contact:
- Marti Boss
- Phone Number: +31243667243
- Email: marti.boss@radboudumc.nl
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Biochemically and clinically proven endogenous congenital hyperinsulinism:
- Unresponsive to medical treatment (diazoxide)
- Indication for 18F-DOPA PET/CT based on mutation analysis
- Standard imaging (18F-DOPA PET/CT) not older than 8 weeks
- <16 years old
- Informed consent signed by parents or legal guardians of the patient.
Exclusion Criteria:
- Genetically proven diffuse CHI (presenting with a homozygous or compound heterozygous ABCC8/KCNJ11 mutation)
- Calculated creatinine clearance below 40 ml/min
- Evidence of other malignancy than insulin producing tumors in conventional imaging (suspicious liver, bone and lung lesions based on CT)
- Age > 16 years
- No signed informed consent
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Only
- Time Perspectives: Prospective
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Expression and distribution of GLP-1R in pancreas of children with CHI
Time Frame: 1 year
|
Comparison of PET quantification with autoradiography and histology
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Comparison of the exendin PET/CT and F-DOPA PET/CT
Time Frame: 1 year
|
Comparison of sensitivity and specificity for localization of focal CHI
|
1 year
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Martin Gotthardt, Prof., Radboud University Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Glucose Metabolism Disorders
- Metabolic Diseases
- Infant, Newborn, Diseases
- Pancreatic Diseases
- Hypoglycemia
- Hyperinsulinism
- Congenital Hyperinsulinism
- Nesidioblastosis
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Anti-Obesity Agents
- Incretins
- Exenatide
Other Study ID Numbers
- NL54275.091.15
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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