Effect of CBD on the Brain

Fragile X Syndrome Clinical Trial

Official title:

Effect of CBD on the GABAergic System in Patients With Fragile X Syndrome.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06261450
• Other study ID #: 2020-3424
• Secondary ID: 236114202010PJT-
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 1, 2024
• Est. completion date: August 15, 2027

Study information

• Verified date: February 2024
• Source: Université de Sherbrooke
• Contact: François Corbin, MD, Ph.D.
• Phone: 819-346-1110
• Email: Francois.Corbin[@]USherbrooke.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: August 15, 2027
• Est. primary completion date: August 15, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 7 Years to 55 Years

Eligibility

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).

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,

Related Conditions & MeSH terms

• Fragile X Syndrome
• Syndrome

Intervention

Drug:
• CBD Oral Solution (eCBD system Target)
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.
• Placebo
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)

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Université de Sherbrooke	Canadian Institutes of Health Research (CIHR), Centre de recherche du Centre hospitalier universitaire de Sherbrooke, Jazz Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Intracortical Facilitation	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).	Comparison between pre and 2 hours post administration of Oral CBD solution and placebo
Secondary	Gaba concentration levels	Estimation of GABA concentrations in the brain from magnetic resonance spectroscopy (MRS)	Comparison between pre and 2 hours post administration of Oral CBD solution and placebo