Ignite Creation Date:
2025-12-25 @ 5:02 AM
Ignite Modification Date:
2025-12-26 @ 4:03 AM
Study NCT ID:
NCT03768518
Status:
UNKNOWN
Last Update Posted:
2018-12-07
First Post:
2018-07-11
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
GLP-1 Receptor Expression in CHI
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D044903', 'term': 'Congenital Hyperinsulinism'}], 'ancestors': [{'id': 'D010182', 'term': 'Pancreatic Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D007232', 'term': 'Infant, Newborn, Diseases'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D006946', 'term': 'Hyperinsulinism'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D007003', 'term': 'Hypoglycemia'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Tumour tissue'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'CASE_ONLY'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 40}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2018-02-07', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-12', 'completionDateStruct': {'date': '2019-02-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2018-12-06', 'studyFirstSubmitDate': '2018-07-11', 'studyFirstSubmitQcDate': '2018-12-06', 'lastUpdatePostDateStruct': {'date': '2018-12-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2018-12-07', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-02-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Expression and distribution of GLP-1R in pancreas of children with CHI', 'timeFrame': '1 year', 'description': 'Comparison of PET quantification with autoradiography and histology'}], 'secondaryOutcomes': [{'measure': 'Comparison of the exendin PET/CT and F-DOPA PET/CT', 'timeFrame': '1 year', 'description': 'Comparison of sensitivity and specificity for localization of focal CHI'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Exendin', 'GLP-1', 'PET/CT'], 'conditions': ['Congenital Hyperinsulinism']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nFurthermore, 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.\n\nThese 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.\n\nObjective:\n\nThe 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.\n\nFurthermore, 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.\n\nAlso, the safety (side-effects) of 68Ga-NODAGA-exendin and 18F-DOPA will be assessed.\n\nFurthermore, dosimetric calculations will be performed and the minimum radioactivity dose of 68Ga-NODAGA-exendin 4 to obtain acceptable/reliable images will be determined.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '16 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'patients (\\<16 years) with biochemically proven endogenous congenital hyperinsulinism', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Biochemically and clinically proven endogenous congenital hyperinsulinism:\n* Unresponsive to medical treatment (diazoxide)\n* Indication for 18F-DOPA PET/CT based on mutation analysis\n* Standard imaging (18F-DOPA PET/CT) not older than 8 weeks\n* \\<16 years old\n* Informed consent signed by parents or legal guardians of the patient.\n\nExclusion Criteria:\n\n* Genetically proven diffuse CHI (presenting with a homozygous or compound heterozygous ABCC8/KCNJ11 mutation)\n* Calculated creatinine clearance below 40 ml/min\n* Evidence of other malignancy than insulin producing tumors in conventional imaging (suspicious liver, bone and lung lesions based on CT)\n* Age \\> 16 years\n* No signed informed consent'}, 'identificationModule': {'nctId': 'NCT03768518', 'acronym': 'GLP-1-CHI', 'briefTitle': 'GLP-1 Receptor Expression in CHI', 'organization': {'class': 'OTHER', 'fullName': 'Radboud University Medical Center'}, 'officialTitle': 'The Physiology of Glucagon-like-peptide-1 Espression in Patients With Endogenous Hyperinsulinism: Correlation With Histopathology', 'orgStudyIdInfo': {'id': 'NL54275.091.15'}}, 'armsInterventionsModule': {'interventions': [{'name': '68Ga-exendin-4 PET/CT', 'type': 'DIAGNOSTIC_TEST', 'description': '68Ga-exendin-4 PET/CT'}]}, 'contactsLocationsModule': {'locations': [{'zip': '6500HB', 'city': 'Nijmegen', 'status': 'RECRUITING', 'country': 'Netherlands', 'contacts': [{'name': 'Marti Boss', 'role': 'CONTACT', 'email': 'marti.boss@radboudumc.nl', 'phone': '+31243667243'}], 'facility': 'Radboudumc', 'geoPoint': {'lat': 51.8425, 'lon': 5.85278}}], 'centralContacts': [{'name': 'Marti Boss', 'role': 'CONTACT', 'email': 'marti.boss@radboudumc.nl', 'phone': '+31243667243'}], 'overallOfficials': [{'name': 'Martin Gotthardt, Prof.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Radboud University Medical Center'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Radboud University Medical Center', 'class': 'OTHER'}, 'collaborators': [{'name': 'European Commission', 'class': 'OTHER'}, {'name': 'University College, London', 'class': 'OTHER'}, {'name': 'Charite University, Berlin, Germany', 'class': 'OTHER'}, {'name': 'University Hospital, Basel, Switzerland', 'class': 'OTHER'}, {'name': 'Insel Gruppe AG, University Hospital Bern', 'class': 'OTHER'}, {'name': 'University of Helsinki', 'class': 'OTHER'}, {'name': 'Turku University Hospital', 'class': 'OTHER_GOV'}, {'name': 'University Medical Center Groningen', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Martin Gotthardt', 'investigatorAffiliation': 'Radboud University Medical Center'}}}}