Effect of CANnabidiol on Anxiety and GABAergic Function in Individuals With Fragile-X Syndrome

ConditionFragile X Syndrome

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age7-40

SponsorUniversité de Sherbrooke

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Molecular diagnosis of FXS

Age 7 to 40 inclusively

Overall ABC-C score > 20

Taking up to 3 psychoactive drugs

Disqualifiers

Taking valproic acid

Taking clobazam

History of liver problems

aspartate aminotransferase (AST) or alanine transaminase (ALT), > 3 times the reference values

Trial design

Design model

Crossover

Treatments tested in this trial

CBD Oral Solution
Drug
Participants will start with oral CBD dose of 5 mg/kg/day for two weeks and then increase to 10 mg/kg/day.
Placebo
Drug
Participants will receive a dose of a placebo composed of the inactive ingredients of CBD of the same volume as the CBD Oral Solution.

Treatment groups

40 Participants

are divided into 2 treatment groups

Group A: CBD FirstExperimental treatment 2 interventions

Group B: Placebo FirstExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

Impact of Oral CBD Solution anxiety.

Caregivers will complete The Anxiety, Depression, and Mood Scale (ADAMS). The ADAMS consists of 29 items on a 4-point scale from 0 (behavior have not occurred or is not a problem) to 3 (behavior occurs a lot, or is a severe problem). It evaluates emotional disturbances along five dimensions: mania/hyperactivity, depressed mood, social avoidance, general anxiety, and obsessive behavior.

Time frame