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| ID | Type | Description | Link |
|---|---|---|---|
| 236114 | Other Identifier | Health Canada | |
| 202010PJT-451514 | Other Grant/Funding Number | Canadian Institutes of Health Research |
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| Name | Class |
|---|---|
| Canadian Institutes of Health Research (CIHR) | OTHER_GOV |
| Jazz Pharmaceuticals | INDUSTRY |
| Centre de recherche du Centre hospitalier universitaire de Sherbrooke | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CBD first | Experimental | A single dose of CBD dose administered followed by a dose of placebo 3 weeks later. |
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| Placebo first | Experimental | A single dose of placebo dose administered followed by a dose of CBD 3 weeks later. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CBD Oral Solution (eCBD system Target) | Drug | Participants 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | Comparison between pre and 2 hours post administration of Oral CBD solution and placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Comparison between pre and 2 hours post administration of Oral CBD solution and placebo |
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Inclusion Criteria:
Eligibility criteria for FXS participants will include:
Eligibility criteria for the control group:
Eligibility Criteria for all Participants:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| François Corbin, MD, Ph.D. | Contact | 819-346-1110 | 15801 | Francois.Corbin@USherbrooke.ca |
| Samantha Cote | Contact | 819-346-1110 | 70184 | Samantha.cote@usherbrooke.ca |
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| ID | Term |
|---|---|
| D005600 | Fragile X Syndrome |
| ID | Term |
|---|---|
| D038901 | X-Linked Intellectual Disability |
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
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This study is a double-blind-crossover placebo control comparing the acute effect of oral CBD in patients with FXS to controls.
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Randomization and dispensing of active and control will be conducted by the research center pharmacy.
| Placebo | Drug | Participants 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) |
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| Gaba concentration levels | Estimation of GABA concentrations in the brain from magnetic resonance spectroscopy (MRS) | Comparison between pre and 2 hours post administration of Oral CBD solution and placebo |
| D009422 | Nervous System Diseases |
| D025064 | Sex Chromosome Disorders |
| D025063 | Chromosome Disorders |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| D040181 | Genetic Diseases, X-Linked |
| D020271 | Heredodegenerative Disorders, Nervous System |