Effect of CBD on the Brain

NCT06261450 | Not Yet Recruiting Phase 2

• 3 other identifiers: 2020-3424236114202010PJT-451514
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Fragile X Syndrome

Keywords

MRI; Cannabidiol; GABA; FXS; MRS; TMS

Outcome Measures

Primary Outcomes (1)

• Short Intracortical Inhibition

  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)

  Comparison between pre and 2 hours post administration of Oral CBD solution and placebo

Secondary Outcomes (2)

• Intracortical Facilitation

  Comparison between pre and 2 hours post administration of Oral CBD solution and placebo

• Gaba concentration levels

  Comparison between pre and 2 hours post administration of Oral CBD solution and placebo

Study Arms (2)

CBD first

EXPERIMENTAL

A single dose of CBD dose administered followed by a dose of placebo 3 weeks later.

Drug: CBD Oral Solution (eCBD system Target); Drug: Placebo

Placebo first

EXPERIMENTAL

A single dose of placebo dose administered followed by a dose of CBD 3 weeks later.

Drug: CBD Oral Solution (eCBD system Target); Drug: Placebo

Interventions

CBD Oral Solution (eCBD system Target) DRUG

Participants receive orally 6 ml of CBD Oral Solution (100 mg / ml; 60 mg / kg; max 600 mg of CBD) followed by 6 ml of a placebo composed of the inactive ingredients of CBD Oral Solution 3 weeks later.

CBD first; Placebo first

Placebo DRUG

Participants receive orally 6 ml of a placebo composed of the inactive ingredients of CBD Oral Solution followed by 6 ml of Oral CBD Solution (100 mg / ml; 60 mg / kg; max 600 mg of CBD)

CBD first; Placebo first

Eligibility Criteria

• Age: 7 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• 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).

You may not qualify if:

• 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,

Sponsors & Collaborators

• Université de Sherbrooke: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Jazz Pharmaceuticals: collaborator
• Centre de recherche du Centre hospitalier universitaire de Sherbrooke: collaborator

MeSH Terms

Conditions

Fragile X Syndrome

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System

Central Study Contacts

François Corbin, MD, Ph.D.

CONTACT

819-346-1110; Francois.Corbin@USherbrooke.ca

Samantha Cote

CONTACT

819-346-1110; Samantha.cote@usherbrooke.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomization and dispensing of active and control will be conducted by the research center pharmacy.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full professor, Department of biochemistry

Model Details: This study is a double-blind-crossover placebo control comparing the acute effect of oral CBD in patients with FXS to controls.

Study Record Dates

• First Submitted: January 26, 2024
• First Posted: February 15, 2024
• Study Start: May 1, 2025
• Primary Completion (Estimated): December 15, 2027
• Study Completion (Estimated): December 15, 2027
• Last Updated: February 17, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share