Fragile X SyndromePhase 2CANAXNCT06261502
Effect of CANnabidiol on Anxiety and GABAergic Function in Individuals With Fragile-X Syndrome
A Phase 2 study testing CBD Oral Solution in people with Fragile X Syndrome, run by Université de Sherbrooke at 1 site in Canada.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 7 to 40 years
- Conditions the study is for
- Fragile X Syndrome
- What is being tested?
- CBD Oral Solution
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteCanada
- Study dates
- 1 Sep 2025to 1 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Universite de Sherbrooke, CHUS Research Center
Sherbrooke, Quebec, J1H5N4
Francois Corbin, MD/PhD, 819-346-1110, francois.corbin@usherbrooke.ca
Amanda Andrews, B.A., 819-346-1110
About this study
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
- Being tested
- CBD Oral Solution, Placebo
- Keywords
- FXS, CBD, TMS, MRI, eCB
- Medical subject headings
- Fragile X Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CBD Oral SolutionDrug
Participants will start with oral CBD dose of 5 mg/kg/day for two weeks and then increase to 10 mg/kg/day.
PlaceboDrug
Participants will receive a dose of a placebo composed of the inactive ingredients of CBD of the same volume as the CBD Oral Solution.
| Study group | Role | What they receive |
|---|---|---|
| CBD First | Experimental | Participants will start with CBD to stimulate the eCB for 12 weeks, undergo an 8-week washout period, and then receive a 12-week placebo. Receives: Drug: CBD Oral Solution; Drug: Placebo |
| Placebo First | Experimental | Participants will start with a placebo for 12 weeks, undergo an 8-week washout period, and then receive a 12-week CBD to stimulate the eCB system. Receives: Drug: CBD Oral Solution; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At baseline, 12 weeks, 20 weeks, and 32 weeks
Impact of Oral CBD Solution on disruptive behavior
Caregivers will complete the Aberrant Behavior Checklist-Community Fragile-X (ABC-C FX). The ABC-C FX has 55 items and is subdivided into explores 6 subdomains: irritability, hyperactivity, lethargy/withdrawal, stereotypy, inappropriate speech, and social avoidance. Higher scores reflect higher aberrant behavior.
ABC-C FX is considered the gold standard for assessing behavioral changes in clinical trials in FXS.
Measured: At baseline, 12 weeks, 20 weeks, and 32 weeks
Impact of Oral CBD Solution on Behavioral Inhibition
Participants will complete the NIH Toolbox Cognitive Battery Flanker Task, a behavioral inhibition task validated in FXS. Global scores range from 0 to 10 and are algorithmically defined using accuracy and reaction time. Higher scores reflect better performance.
Measured: At baseline, 12 weeks, 20 weeks, and 32 weeks
Secondary outcomes (3)
Impact of Oral CBD Solution on intracortical inhibition
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)
Measured: At baseline, 12 weeks, 20 weeks, and 32 weeks
Impact of Oral CBD Solution on intracortical facilitation
Transcranial magnetic stimulation (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).
Measured: At baseline, 12 weeks, 20 weeks, and 32 weeks
Impact of Oral CBD Solution on
Estimation of GABA concentrations in the brain from magnetic resonance spectroscopy
Measured: At baseline, 12 weeks, 20 weeks, and 32 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2024
- Study start1 Sep 2025
- Primary completion1 Jul 2028 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fragile X SyndromeStudies of the same condition, open and under way.
- More trials run by Université de SherbrookeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, Double-blind, placebo-controlled, single center, cross-over trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Université de Sherbrooke
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Jazz Pharmaceuticals, Centre de recherche du Centre hospitalier universitaire de Sherbrooke
- Responsible party
- Principal investigator, Francois Corbin, Université de Sherbrooke
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06261502
- Sponsor's protocol ID
- 2023-4527
- Other IDs
- 275882, 202010PJT-451514
- Acronym
- CANAX
- Status last verified
- Aug 2026
- First submitted
- 26 Jan 2024
- Last updated
- 28 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of CANnabidiol on Anxiety and GABAergic Function in Individuals With Fragile-X Syndrome
- ClinicalTrials.gov ID
- NCT06261502
- Acronym / sponsor ID
- CANAX / 2023-4527
- Conditions
- Fragile X Syndrome
- Keywords
- FXS, CBD, TMS, MRI, eCB
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Université de SherbrookeUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Jazz Pharmaceuticals, Centre de recherche du Centre hospitalier universitaire de Sherbrooke
- Study start
- 1 Sep 2025 (actual)
- Primary completion
- 1 Jul 2028 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 15 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, Double-blind, placebo-controlled, single center, cross-over trial
| Arm | Type | Receives |
|---|---|---|
| CBD First | Experimental | Drug: CBD Oral Solution, Drug: PlaceboParticipants will start with CBD to stimulate the eCB for 12 weeks, undergo an 8-week washout period, and then receive a 12-week placebo. |
| Placebo First | Experimental | Drug: CBD Oral Solution, Drug: PlaceboParticipants will start with a placebo for 12 weeks, undergo an 8-week washout period, and then receive a 12-week CBD to stimulate the eCB system. |
Who may qualify
- Ages
- 7 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CBD Oral SolutionParticipants will start with oral CBD dose of 5 mg/kg/day for two weeks and then increase to 10 mg/kg/day. | Drug | CBD First, Placebo First |
| PlaceboParticipants will receive a dose of a placebo composed of the inactive ingredients of CBD of the same volume as the CBD Oral Solution. | Drug | CBD First, Placebo First |
Primary outcome
Impact of Oral CBD Solution anxiety.
Time frame: At baseline, 12 weeks, 20 weeks, and 32 weeks
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.
Impact of Oral CBD Solution on disruptive behavior
Time frame: At baseline, 12 weeks, 20 weeks, and 32 weeks
Caregivers will complete the Aberrant Behavior Checklist-Community Fragile-X (ABC-C FX). The ABC-C FX has 55 items and is subdivided into explores 6 subdomains: irritability, hyperactivity, lethargy/withdrawal, stereotypy, inappropriate speech, and social avoidance. Higher scores reflect higher aberrant behavior. ABC-C FX is considered the gold standard for assessing behavioral changes in clinical trials in FXS.
Impact of Oral CBD Solution on Behavioral Inhibition
Time frame: At baseline, 12 weeks, 20 weeks, and 32 weeks
Participants will complete the NIH Toolbox Cognitive Battery Flanker Task, a behavioral inhibition task validated in FXS. Global scores range from 0 to 10 and are algorithmically defined using accuracy and reaction time. Higher scores reflect better performance.
3 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CBD Oral Solution in people with Fragile X Syndrome, run by Université de Sherbrooke at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact François Corbin, MD, Ph.D. (819-346-1110 ext. 15801, Francois.Corbin@USherbrooke.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Impact of Oral CBD Solution anxiety. (time frame: At baseline, 12 weeks, 20 weeks, and 32 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2026.