E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult endogenous hyperinsulinemic hypoglycemia |
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E.1.1.1 | Medical condition in easily understood language |
High blood insulin levels with low blood glucose levels in adults |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 comparison of 68Ga-NODAGA-exendin-4 (alternatively 111In-DTPA-Exendin-4) with 68Ga-DOTATOC PET/CT (alternatively 68Ga-DOTATATE or 111In-DTPA-octreotide)) in order to determine the sensitivity and (specificity) of new imaging method as well as 68Ga-DOTATOC PET/CT for preoperative visualization of diseased beta cells. We will assess the positive predictive values and diagnostic odds ratio of the different techniques according to intra-operative findings, histology and clinical outcome. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
• Comparison of 68Ga-NODAGA-exendin-4 (alternatively 111In-DTPA-Exendin-4) with standard imaging (eg. triple phase CT, MRI, endoscopic ultrasound)
• Calculating the organ- and effective dose of 68Ga-NODAGA-exendin 4 on the basis of quantification of serial PET images in a subgroup of 6 patients.
• Impact on clinical management of GLP-1R imaging, e.g. possible use of GLP-1R imaging as standard for preoperative imaging in AHH.
• Calculating and comparing the interobserver variability of 68Ga-NODAGA-exendin 4 PET/CT (alternatively 111In-DTPA-AHX-Lys40-Exendin 4 SPECT/CT) combined with triple phase CT or MRI
• Comparing imaging parameters (SUVmax), intraoperative findings, histology and GLP-1/sst2 receptor expression by in vitro autoradiography on frozen tissue samples
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Biochemically proven endogenous hyperinsulinemic hypoglycemia: neuroglycopenic symptoms in the fasting state with low plasma glucose, inappropriately high serum insulin and C-peptide concentrations
• Signed informed consent
• Standard imaging not older than 8 weeks. This includes a triple-phase CT or MRI, somatostatin receptor imaging (68Ga-DOTATOC, 68Ga-DOTATATE or 111In-DTPA-octreotide SPECT/CT) and endocopic ultrasound (EUS). Protocols that should be followed for these procedures can be found in the annex.
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E.4 | Principal exclusion criteria |
• Breast feeding
• Pregnancy or the wish to become pregnant within 6 months
• Calculated creatinine clearance below 40ml/min
• Evidence of other malignancy than insulin producing tumors in conventional imaging (suspicious liver, bone and lung lesions)
• Age < 18 years
• No signed informed consent
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E.5 End points |
E.5.1 | Primary end point(s) |
Comparison of sensitivity, specificity, positive predictive value, diagnostic odds ratio and receiver operating characteristics between 68Ga-NODAGA-exendin 4 (alternatively 111In-DTPA-Exendin 4) and conventional imaging such as triple phase CT, MRI, F-18-DOPA, C-11-HTP and 68Ga-DOTATOC (alternatively 68Ga-DOTATATE-PET/CT or 111In-DTPA-octreotide) in adult patients with biochemically proven endogenous hyperinsulinemic hypoglycemia in the fasting state. |
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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) |
• Calculation of the organ- and effective dose of 68Ga-NODAGA-exendin 4
• Assessing the impact on clinical management of GLP-1R imaging
• Calculation and comparison of the interobserver variability of 68Ga-NODAGA-exendin 4 PET/CT (alternatively 111In-DTPA-AHX-Lys40-Exendin 4 SPECT/CT) and EUS combined with triple phase CT or MRI
• Comparison of imaging parameters (SUVmax), intraoperative findings, histology and GLP-1/sst2 receptor expression in vitro autoradiography on frozen tissue samples
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After collection of data of 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 | No |
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 techniques |
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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 | 9 |
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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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 | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |