GLP-1 Receptor Expression in CHI (GLP-1-CHI)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03768518|
Recruitment Status : Recruiting
First Posted : December 7, 2018
Last Update Posted : December 7, 2018
|Condition or disease||Intervention/treatment|
|Congenital Hyperinsulinism||Diagnostic Test: 68Ga-exendin-4 PET/CT|
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.
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|
|Estimated Enrollment :||40 participants|
|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|
- Diagnostic Test: 68Ga-exendin-4 PET/CT
- Expression and distribution of GLP-1R in pancreas of children with CHI [ Time Frame: 1 year ]Comparison of PET quantification with autoradiography and histology
- 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
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
|Contact: Marti Bossemail@example.com|
|Nijmegen, Netherlands, 6500HB|
|Contact: Marti Boss +31243667243 firstname.lastname@example.org|
|Principal Investigator:||Martin Gotthardt, Prof.||Radboud University|