protocolSection identificationModule nctId: NCT06261502, orgStudyIdInfo id: 2023-4527, secondaryIdInfos id: 275882, type: OTHER, domain: Health Canada, secondaryIdInfos 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, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-04-01, primaryCompletionDateStruct date: 2027-05-01, completionDateStruct date: 2027-08-01, studyFirstPostDateStruct date: 2024-02-15, lastUpdatePostDateStruct date: 2024-02-15, sponsorCollaboratorsModule leadSponsor name: Université de Sherbrooke, class: OTHER, collaborators name: Canadian Institutes of Health Research (CIHR), collaborators name: Jazz Pharmaceuticals, collaborators name: Centre de recherche du Centre hospitalier universitaire de Sherbrooke, descriptionModule 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., conditionsModule conditions: Fragile X Syndrome, designModule studyType: INTERVENTIONAL, phases: PHASE2, designInfo allocation: RANDOMIZED, interventionModel: CROSSOVER, interventionModelDescription: Randomized, Double-blind, placebo-controlled, single center, cross-over trial, primaryPurpose: TREATMENT, maskingInfo 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, enrollmentInfo count: 40, type: ESTIMATED, armsInterventionsModule interventions name: CBD Oral Solution, interventions name: Placebo, outcomesModule primaryOutcomes measure: Impact of Oral CBD Solution anxiety., primaryOutcomes measure: Impact of Oral CBD Solution on disruptive behavior, primaryOutcomes measure: Impact of Oral CBD Solution on Behavioral Inhibition, secondaryOutcomes measure: Impact of Oral CBD Solution on intracortical inhibition, secondaryOutcomes measure: Impact of Oral CBD Solution on intracortical facilitation, secondaryOutcomes measure: Impact of Oral CBD Solution on, eligibilityModule sex: ALL, minimumAge: 7 Years, maximumAge: 40 Years, stdAges: CHILD, stdAges: ADULT, contactsLocationsModule, hasResults: False