E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Congenital hyperinsulinism |
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E.1.1.1 | Medical condition in easily understood language |
Low blood glucose levels due to congenital overproduction of insulin |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061211 |
E.1.2 | Term | Hyperinsulinism |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main study aim is the in vivo and ex vivo investigation of the expression and distribution of the GLP-1R in the pancreas of children (< 16 years) with proven endogenous congenital hyperinsulinism who qualify for surgery based on response to medical treatment and genetic analysis (only patients with genetically proven diffuse CHI will be excluded). 68Ga-NODAGA-exendin-4 PET/CT imaging data will be compared with autoradiography and histology performed on specimens collected during surgery. |
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E.2.2 | Secondary objectives of the trial |
• Comparing 68Ga-NODAGA-exendin-4 PET/CT and 18F-DOPA PET/CT in order to determine the sensitivity of the new imaging method.
• Analyzing kinetics of radiotracer uptake in the pancreas of CHI patients by dynamic PET scans in 5 patients.
• Determining the lowest activity dose of 68Ga-NODAGA-exendin 4 needed for accurate imaging.
• Performing dosimetric studies to determine the radiation dose received by children injected with this calculated minimum dose of 68Ga-NODAGA-exendin 4 based on whole-body PET/CT scans performed in 2 patients.
• Assessing the safety (side effects) of 68Ga-NODAGA-exendin 4 as compared to 18F-DOPA
• Calculating and comparing the interobserver variability of 68Ga-NODAGA-exendin 4 PET/CT and 18F-DOPA PET/CT
• Evaluating the clinical outcome parameters (laboratory parameters (glucose), dosage of medical treatment) after surgery
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The expression and distribution of the GLP-1R in the pancreas of children (<16 years) with proven endogenous congenital hyperinsulinism by comparison of 68Ga-NODAGA-exendin 4 PET/CT imaging data with autoradiography and histology performed on specimens collected during surgery |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After collection of data from each patient and at the end of the study |
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E.5.2 | Secondary end point(s) |
• Comparison of the sensitivity of 68Ga-NODAGA-exendin 4 PET/Ct and 18F-DOPA PET/CT for the pre-operative localization of focal CHI and the discrimination between focal and diffuse CHI.
• Analysis of the kinetics of radiotracer uptake in the pancreas of CHI patients.
• Determination of the minimal injected dose of 68Ga-NODAGA-exendin 4 needed for accurate imaging.
• Determination of the effective radiation dose received by children injected with the calculated minimum dose of 68Ga-NODAGA-exendin 4.
• Assessment of the safety (side effects) of 68Ga-NODAGA-exendin 4 as compared to 18F-DOPA.
• Calculation and comparison of the interobserver variability of 68Ga-NODAGA-exendin 4 PET/CT and 18F-DOPA PET/CT
• Evaluation of the clinical outcome parameters (laboratory parameters (glucose) and dosage of medical treatment) after surgery |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After collection of data from all patients |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard imaging technique |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |