GLP-1 Receptor Expression in CHI

NCT ID: NCT03768518

Last Updated: 2018-12-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

40 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-02-07

Study Completion Date

2019-02-01

Brief Summary

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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

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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.

Conditions

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Congenital Hyperinsulinism

Keywords

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Exendin GLP-1 PET/CT

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Interventions

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68Ga-exendin-4 PET/CT

68Ga-exendin-4 PET/CT

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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
Maximum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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European Commission

OTHER

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role collaborator

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role collaborator

University of Helsinki

OTHER

Sponsor Role collaborator

Turku University Hospital

OTHER_GOV

Sponsor Role collaborator

University Medical Center Groningen

OTHER

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Martin Gotthardt

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Martin Gotthardt, Prof.

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

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Radboudumc

Nijmegen, , Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Marti Boss

Role: CONTACT

Phone: +31243667243

Email: [email protected]

Facility Contacts

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Marti Boss

Role: primary

Other Identifiers

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NL54275.091.15

Identifier Type: -

Identifier Source: org_study_id