Effect of CANnabidiol on Anxiety and GABAergic Function in Individuals with Fragile-X Syndrome
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: CBD Oral Solution, Placebo.
- Who it may be relevant to
- Registry conditions: Fragile X Syndrome. Basic parameters: 7 years — 40 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Center list to be confirmed — check the primary protocol.
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
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.
Interventions
- Drug CBD Oral Solution
Participants will start with oral CBD dose of 5 mg/kg/day for two weeks and then increase to 10 mg/kg/day. - Drug Placebo
Participants will receive a dose of a placebo composed of the inactive ingredients of CBD of the same volume as the CBD Oral Solution.
Primary outcome measures
- Impact of Oral CBD Solution anxiety. [Time frame: At baseline, 12 weeks, 20 weeks, and 32 weeks]
- Impact of Oral CBD Solution on disruptive behavior [Time frame: At baseline, 12 weeks, 20 weeks, and 32 weeks]
- Impact of Oral CBD Solution on Behavioral Inhibition [Time frame: At baseline, 12 weeks, 20 weeks, and 32 weeks]
Secondary outcome measures (3)
- Impact of Oral CBD Solution on intracortical inhibition [Time frame: At baseline, 12 weeks, 20 weeks, and 32 weeks]
- Impact of Oral CBD Solution on intracortical facilitation [Time frame: At baseline, 12 weeks, 20 weeks, and 32 weeks]
- Impact of Oral CBD Solution on [Time frame: At baseline, 12 weeks, 20 weeks, and 32 weeks]
Eligibility criteria
Inclusion criteria
- Molecular diagnosis of FXS
- Age 7 to 40 inclusively
- Overall ABC-C score > 20
- Taking up to 3 psychoactive drugs
- No therapeutic change for the last 3 months
Exclusion criteria
- Taking valproic acid
- Taking clobazam
- History of liver problems
- aspartate aminotransferase (AST) or alanine transaminase (ALT), > 3 times the reference values
- Bilirubin > 2 times the reference values
- Absolute contraindication to the use of TMS and MRI (e.g. presence of metal in the body), will also be considered as an exclusion criterion.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Crossover
- Masking
- Quadruple blind
- Primary purpose
- Treatment
Study locations
Center list to be confirmed — check the primary protocol.
Identifiers
NCT: NCT06261502 · 2023-4527 · 275882 · 202010PJT-451514