About this trial
This proposal focuses on the therapeutic relevance of the endocannabinoid (eCB) system for the treatment of Fragile-X syndrome (FXS), the primary hereditary cause of autism spectrum disorder (ASD). Although most individuals with FXS have moderate to severe intellectual disability (ID), caregivers are mainly concerned about aggressive behavior and anxiety problems, hallmark features of the condition. Concurrent lines of evidence suggest that targeting the endocannabinoid (eCB) system by administration of cannabidiol (CBD) could upregulate GABAergic functions and correct inhibitory deficits presumed responsible for the neuropsychiatric phenotype of FXS. However, the eCB system and its effect on the brain remains unexplored in FXS patients. This clinical trial aims to define the therapeutic relevance of the eCB system for FXS using a multimodal neuroimaging approach to finely characterize the acute effects of oral CBD on the principal inhibitory neurotransmitter system (GABA) in a large cohort of FXS patients.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
age between 7 and 55 years, molecular diagnosis of FXS,
intelligence quotient (IQ) <70,
aberrant behavior questionnaire score (ABC-C) > 20,
<3 psychoactive drugs, drug stable for > 3 months.
Disqualifiers
The presence of an absolute contraindication to the use of TMS and MRI / MRS (ie presence of metal in the head).
Individuals with ALT / ASL levels greater than 3 times the upper normal baseline, or if bilirubin exceeds 2 times the upper baseline,
Trial design
Crossover
Treatments tested in this trial
CBD Oral Solution (eCBD system Target)
DrugParticipants receive orally 6 ml of CBD Oral Solution (100 mg / ml; 60 mg / kg; max 600 mg of CBD) followed by 6 ml of a placebo composed of the inactive ingredients of CBD Oral Solution 3 weeks later.
Placebo
DrugParticipants receive orally 6 ml of a placebo composed of the inactive ingredients of CBD Oral Solution followed by 6 ml of Oral CBD Solution (100 mg / ml; 60 mg / kg; max 600 mg of CBD)
Treatment groups
Trial outcomes
Primary outcomes
Short Intracortical Inhibition
Transcranial Magnetic Stimulation (TMS)-derived measure of Intracortical inhibition: The degree of decrease of peak-to-peak motor evoked potential (MEP) amplitude induced by the administration of a conditioning stimulus (set at 70% of resting motor threshold) 2-4 ms before the test stimulus (stimulation intensity required to produce an MEP of 1 millivolt (mV), approximately 120% of resting motor threshold)
Secondary outcomes
Intracortical Facilitation
TMS-derived measure of Intracortical Facilitation: The degree of increase of peak-to-peak motor evoked potential (MEP) amplitude induced by the administration of a conditioning stimulus (set at 80% of resting motor threshold) 12-24 ms before the test stimulus (stimulation intensity required to produce an MEP of 1 mV, approximately 120% of resting motor threshold).
Gaba concentration levels
Estimation of GABA concentrations in the brain from magnetic resonance spectroscopy (MRS)
Locations
Sponsors and contacts
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Université de Sherbrooke
Lead sponsor
Canadian Institutes of Health Research (CIHR)
Collaborator
Jazz Pharmaceuticals
Collaborator
Centre de recherche du Centre hospitalier universitaire de Sherbrooke
Collaborator
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