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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

Tracking Information
First Submitted Date July 11, 2018
First Posted Date December 7, 2018
Last Update Posted Date December 7, 2018
Actual Study Start Date February 7, 2018
Estimated Primary Completion Date February 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: December 6, 2018)
Expression and distribution of GLP-1R in pancreas of children with CHI [ Time Frame: 1 year ]
Comparison of PET quantification with autoradiography and histology
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: December 6, 2018)
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
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title GLP-1 Receptor Expression in CHI
Official Title The Physiology of Glucagon-like-peptide-1 Espression in Patients With Endogenous Hyperinsulinism: Correlation With Histopathology
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.
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 Observational
Study Design Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Tumour tissue
Sampling Method Non-Probability Sample
Study Population patients (<16 years) with biochemically proven endogenous congenital hyperinsulinism
Condition Congenital Hyperinsulinism
Intervention Diagnostic Test: 68Ga-exendin-4 PET/CT
68Ga-exendin-4 PET/CT
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: December 6, 2018)
40
Original Estimated Enrollment Same as current
Estimated Study Completion Date February 1, 2019
Estimated Primary Completion Date February 1, 2019   (Final data collection date for primary outcome measure)
Eligibility 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
Sex/Gender
Sexes Eligible for Study: All
Ages up to 16 Years   (Child)
Accepts Healthy Volunteers No
Contacts
Contact: Marti Boss +31243667243 marti.boss@radboudumc.nl
Listed Location Countries Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number NCT03768518
Other Study ID Numbers NL54275.091.15
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Martin Gotthardt, Radboud University
Study Sponsor Radboud University
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
Investigators
Principal Investigator: Martin Gotthardt, Prof. Radboud University
PRS Account Radboud University
Verification Date December 2018