E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ghrelin levels in patients with Prader Willi Syndrome and healthy controls and response of ghrelin levels to a single exenatide injection compared with placebo (0.9% sodium chloride) injection. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036476 |
E.1.2 | Term | Prader-Willi syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic 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 |
To investigate the effects of exenatide (a synthetic compound which is currently licensed and used as a treatment option in type 2 diabetes that has well described appetite supressing and weight-losing properties) on circulating ghrelin levels (a hormone produced by the stomach), appetite and food intake in subjects with PWS. |
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E.2.2 | Secondary objectives of the trial |
We will also analyse the expression of adipokines (fat hormones) in subcutaneous adipose (fat) tissue, obtained by needle biopsy, in subjects with Prader Willi Syndrome compared to weight and adiposity-matched controls. This will allow us to explore possible links with the abnormal body composition and fat distribution observed in Prader Willi Syndrome subjects. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with Prader-Willi Syndrome with inadequately controlled body weight (BMI > 25 kg/m2), and healthy volunteers (without diabetes), matched for age and adiposity. |
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E.4 | Principal exclusion criteria |
For the Prader Willi Syndrome group: patients with Prader Willi Syndrome with adequately controlled body weight (BMI < 25 kg/m2) will be excluded for safety reasons (see above). Also patients with type 1 or 2 diabetes mellitus will be excluded. Exclusion criteria for control participants have been chosen because they will have a direct influence on eating behaviour and patterns. Participants with the following will be excluded: a history of eating disorder such as bulimia nervosa, anorexia nervosa or binge−eating disorder (according to DSM IV criteria), history of psychiatric disorder (schizophrenia, major depression, bipolar affective disorder), diabetes mellitus (type 1 or 2), current history of excess alcohol consumption or substance abuse or addiction, current (or within last 3 months) use of certain centrally acting medication (certain psychotropic or antidepressant medications) that are known to influence feeding behaviour, a history of traumatic brain injury, genetic forms of hypothalamic obesity (such as Prader−Willi syndrome, Biedl−Bardet syndrome). For all participants: the presence of metal implants or metal objects on the body which cannot be removed (those fitted with a heart pacemaker, mini−defibrillator or neurostimulator or have an artificial heart valve; surgical clips in the head; history of injury which may have left metal particles in the eye, head, or elsewhere in the body) will be excluded from the abdominal MRI aspect of the study, as these factors would pose a safety risk to the participant. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure of our proposed study will be the effects of exenatide on circulating ghrelin levels, ghrelin isoforms, appetite rating and food intake in subjects with PWS. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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 | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |