Effect of CBD on the Brain

Phase 2

Not yet recruiting

• Conditions: Fragile X Syndrome
• Interventions: Drug: CBD Oral Solution (eCBD system Target); Drug: Placebo

• Registration Number: NCT06261450
• Lead Sponsor: Université de Sherbrooke

Brief Summary

This proposal 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). Although most individuals with FXS have moderate to severe intellectual disability (ID), caregivers are mainly concerned about aggressive behavior and anxiety problems, hallmark features of the condition. Concurrent lines of evidence suggest that targeting the endocannabinoid (eCB) system by administration of cannabidiol (CBD) could upregulate GABAergic functions and correct inhibitory deficits presumed responsible for the neuropsychiatric phenotype of FXS. However, the eCB system and its effect on the brain remains unexplored in FXS patients. This clinical trial aims to define the therapeutic relevance of the eCB system for FXS using a multimodal neuroimaging approach to finely characterize the acute effects of oral CBD on the principal inhibitory neurotransmitter system (GABA) in a large cohort of FXS patients.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-01-26
• Study First Submitted QC: 2024-02-07
• Study First Posted: 2024-02-15
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-14
• Last Update Posted: 2024-08-15
• Study Start: 2024-10-01
• Primary Completion: 2027-08-15
• Study Completion: 2027-08-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Eligibility criteria for FXS participants will include:

• age between 7 and 55 years, molecular diagnosis of FXS,
• intelligence quotient (IQ) <70,
• aberrant behavior questionnaire score (ABC-C) > 20,
• <3 psychoactive drugs, drug stable for > 3 months.

Eligibility criteria for the control group:

• 18 and 55 years old,
• be in good general health, with no history of neurological or psychiatric disorders.

Eligibility Criteria for all Participants:

• A minimum weight of 60 kg;
• no history of liver problems (A complete blood profile to measure liver enzyme levels (bilirubin, aspartate aminotransferase (AST), argininosuccinate lyase (ASL), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT)) will be obtained before randomization for all participants).

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Exclusion Criteria

• The presence of an absolute contraindication to the use of TMS and MRI / MRS (ie presence of metal in the head).
• Individuals with ALT / ASL levels greater than 3 times the upper normal baseline, or if bilirubin exceeds 2 times the upper baseline,

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
CBD first	CBD Oral Solution (eCBD system Target)	A single dose of CBD dose administered followed by a dose of placebo 3 weeks later.
CBD first	Placebo	A single dose of CBD dose administered followed by a dose of placebo 3 weeks later.
Placebo first	CBD Oral Solution (eCBD system Target)	A single dose of placebo dose administered followed by a dose of CBD 3 weeks later.
Placebo first	Placebo	A single dose of placebo dose administered followed by a dose of CBD 3 weeks later.

Primary Outcome Measures

Name	Time	Method
Short Intracortical Inhibition	Comparison between pre and 2 hours post administration of Oral CBD solution and placebo	Transcranial Magnetic Stimulation (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)

Secondary Outcome Measures

Name	Time	Method
Intracortical Facilitation	Comparison between pre and 2 hours post administration of Oral CBD solution and placebo	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).
Gaba concentration levels	Comparison between pre and 2 hours post administration of Oral CBD solution and placebo	Estimation of GABA concentrations in the brain from magnetic resonance spectroscopy (MRS)