E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fragile X syndrome is the most common form of inherited mental retardation with a prevalence of 1/4000 males and 1/6000 females. Patients are characterized by a mild to severe form of cognitive impairment and light dysmorphic features. Autism-like behaviour, hyperactivity and epilepsy can also be associated with the disease. On the molecular level the disease is caused by a dynamic mutation of a CGG repeat in the 5' UTR of the FMR1 gene. |
|
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
It is our aim to investigate the functional consequences of our previous findings from animal studies, i.e. the physiological consequences of decreased expression of specific GABA(A)receptor subunits. Using Positron Emission Tomography (PET) with [11C]flumazenil we want to image and quantify the GABA(A)receptor distribution in fragile X patients and compare this with controls. |
|
E.2.2 | Secondary objectives of the trial |
Using a battery of tests such as 24h EEG control, movement analysis, neuropsychological tests and a MRI scan, we would like to measure neuropsychologic (cognitive impairment, executive functioning) and behavioural (gait ataxia, action tremor, parkinsonism, neuropathy, autonomic failure..) parameters to investigate a behavioural correlaton of the regional PET GABA(A)receptor findings between patients and controls. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Controls: Males between 18-50 years old, general good health after physical examination and routine laboratory analysis, normal T1 and T2 brain MRI, body weight. Patients: Males between 16-50 years old, need to be approved by the investigators to undergo a 60 minutes PET imaging study.
|
|
E.4 | Principal exclusion criteria |
Controls and patients: Drug abuse, hypersensitivity to drugs or flumazenil or benzodiazepines. No history of other neurological or psychiatric abnormalities or any other major internal abnormality. Medication which interacts with the GABA-system, in particular sleep enhancing medication, is not allowed within two weeks before and after the study, neither drinking more than 3 caffein-containing glasses. Current smokers (more than 5 sigarettes per day) and smokers who quitted less than three months ago will be excluded. Alcohol is prohibited as from 2 days before the beginning of the study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1/ Image quantification of GABA-A receptor binding in Fragile X patients versus controls 2/ relationship of any clinical abnormality to (decreased) GABA-A receptor binding |
|
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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Functional consequences of finding on RNA levels in animal models for the disease |
|
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) | No |
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 |
control group without Fragile X |
|
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 | Information not present in EudraCT |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |