nctId: NCT06261502 id: 2023-4527 id: 275882 type: OTHER domain: Health Canada id: 202010PJT-451514 type: OTHER_GRANT domain: Canadian Institutes of Health Research briefTitle: Effect of CANnabidiol on Anxiety and GABAergic Function in Individuals With Fragile-X Syndrome acronym: CANAX overallStatus: NOT_YET_RECRUITING date: 2024-04-01 date: 2027-05-01 date: 2027-08-01 date: 2024-02-15 date: 2024-02-15 name: Université de Sherbrooke class: OTHER name: Canadian Institutes of Health Research (CIHR) name: Jazz Pharmaceuticals name: Centre de recherche du Centre hospitalier universitaire de Sherbrooke briefSummary: This study 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). Most individuals with FXS have moderate to severe intellectual disability (ID), and caregivers are mainly concerned about aggressive behavior and anxiety problems. Since FXS individuals have a normal lifespan, the overall lifetime cost for the Canadian society of a single case is estimated at $1.2 to $4.7 millions reaching $18 billions for all FXS cases. There is no cure for FXS, as all clinical trials so far have been unsuccessful.FXS is caused by transcriptional silencing of the Fragile X mental retardation protein (FMR1) gene, making FXS a simple model to study ASD and ID pathophysiological mechanisms. Of those, neuronal hyperexcitability is largely recognized as a core deficit in FXS, and a critical therapeutic target for the disorder. Using transcranial magnetic stimulation (TMS) in FXS patients, our team provided the first direct evidence of Gamma-aminobutyric acid (GABA) receptor a (GABAa) dysfunctions in humans with this disorder and showed that this inhibitory deficit is linked with cortical hyperexcitability (PMID: 31748507). Concurrent lines of evidence suggest that stimulation of the endocannabinoid (eCB) system with the administration of Cannabidiol (CBD) could upregulate GABAergic function and correct inhibitory deficits presumed responsible for the neuropsychiatric phenotype of FXS. CBD has been shown to increase GABA concentration levels in the brains of healthy individuals, an effect that could help correct the hyperexcitability typically found in FXS. Thus, this trial aims to define the therapeutic potential of the eCB system for FXS, by measuring the impacts of oral CBD administration on the principal inhibitory neurotransmitter system of FXS patients, and the severity of the clinical phenotype. conditions: Fragile X Syndrome studyType: INTERVENTIONAL phases: PHASE2 allocation: RANDOMIZED interventionModel: CROSSOVER interventionModelDescription: Randomized, Double-blind, placebo-controlled, single center, cross-over trial primaryPurpose: TREATMENT masking: QUADRUPLE maskingDescription: The randomization and participant code allocation process will be carried out by the Centre de recherche du Centre hospitalier universitaire de Sherbrooke (CRCHUS) pharmacy. The pharmacy will dispense the medication or placebo based on the randomization. The principal investigators, Drs. Lepage and Corbin and the research, as well as the participants and their caregivers, will never be aware of the randomization. To avoid any suspicions on the part of the investigators, Dr. Artuela Çaku, who is not part of the research team, will have access to the laboratory results. In the event of an adverse drug effect, Dr. Çaku may break the code to make a more informed decision for the patient's well-being, such as discontinuing participation or reducing the dose, etc. whoMasked: PARTICIPANT whoMasked: CARE_PROVIDER whoMasked: INVESTIGATOR whoMasked: OUTCOMES_ASSESSOR count: 40 type: ESTIMATED name: CBD Oral Solution name: Placebo measure: Impact of Oral CBD Solution anxiety. measure: Impact of Oral CBD Solution on disruptive behavior measure: Impact of Oral CBD Solution on Behavioral Inhibition measure: Impact of Oral CBD Solution on intracortical inhibition measure: Impact of Oral CBD Solution on intracortical facilitation measure: Impact of Oral CBD Solution on sex: ALL minimumAge: 7 Years maximumAge: 40 Years stdAges: CHILD stdAges: ADULT hasResults: False