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GLP-1 Receptor Expression in CHI (GLP-1-CHI)

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ClinicalTrials.gov Identifier: NCT03768518
Recruitment Status : Recruiting
First Posted : December 7, 2018
Last Update Posted : December 7, 2018
Sponsor:
Collaborators:
European Commission
University College, London
Charite University, Berlin, Germany
University Hospital, Basel, Switzerland
University Hospital Inselspital, Berne
Helsinki University
Turku University Hospital
University Medical Center Groningen
Information provided by (Responsible Party):
Martin Gotthardt, Radboud University

Brief Summary:
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.

Condition or disease Intervention/treatment
Congenital Hyperinsulinism Diagnostic Test: 68Ga-exendin-4 PET/CT

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.


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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: The Physiology of Glucagon-like-peptide-1 Espression in Patients With Endogenous Hyperinsulinism: Correlation With Histopathology
Actual Study Start Date : February 7, 2018
Estimated Primary Completion Date : February 1, 2019
Estimated Study Completion Date : February 1, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Exenatide


Intervention Details:
  • Diagnostic Test: 68Ga-exendin-4 PET/CT
    68Ga-exendin-4 PET/CT


Primary Outcome Measures :
  1. Expression and distribution of GLP-1R in pancreas of children with CHI [ Time Frame: 1 year ]
    Comparison of PET quantification with autoradiography and histology


Secondary Outcome Measures :
  1. 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


Biospecimen Retention:   Samples With DNA
Tumour tissue


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
patients (<16 years) with biochemically proven endogenous congenital hyperinsulinism
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03768518


Contacts
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Contact: Marti Boss +31243667243 marti.boss@radboudumc.nl

Locations
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Netherlands
Radboudumc Recruiting
Nijmegen, Netherlands, 6500HB
Contact: Marti Boss    +31243667243    marti.boss@radboudumc.nl   
Sponsors and Collaborators
Radboud University
European Commission
University College, London
Charite University, Berlin, Germany
University Hospital, Basel, Switzerland
University Hospital Inselspital, Berne
Helsinki University
Turku University Hospital
University Medical Center Groningen
Investigators
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Principal Investigator: Martin Gotthardt, Prof. Radboud University

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Responsible Party: Martin Gotthardt, Professor, Radboud University
ClinicalTrials.gov Identifier: NCT03768518     History of Changes
Other Study ID Numbers: NL54275.091.15
First Posted: December 7, 2018    Key Record Dates
Last Update Posted: December 7, 2018
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Martin Gotthardt, Radboud University:
Exendin
GLP-1
PET/CT

Additional relevant MeSH terms:
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Hyperinsulinism
Congenital Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Pancreatic Diseases
Digestive System Diseases
Infant, Newborn, Diseases
Hypoglycemia
Glucagon-Like Peptide 1
Exenatide
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Hypoglycemic Agents
Anti-Obesity Agents