Clinical trial NCT06261450: Effect of CBD on the Brain
Official title: Effect of CBD on the GABAergic System in Patients with Fragile X Syndrome.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Fragile X Syndrome
Keywords: MRI
Cannabidiol
GABA
FXS
MRS
TMS
Lead sponsor: Université de Sherbrooke
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Jazz Pharmaceuticals
name: Centre de recherche du Centre hospitalier universitaire de Sherbrooke
First posted: 2024-02-15
Enrollment: 50
Sex: ALL
Minimum age (years): 7
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This study is a double-blind-crossover placebo control comparing the acute effect of oral CBD in patients with FXS to controls.
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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,

Primary outcomes:
measure: Short Intracortical Inhibition
timeFrame: Comparison between pre and 2 hours post administration of Oral CBD solution and placebo
Secondary outcomes:
measure: Intracortical Facilitation
timeFrame: Comparison between pre and 2 hours post administration of Oral CBD solution and placebo
measure: Gaba concentration levels
timeFrame: Comparison between pre and 2 hours post administration of Oral CBD solution and placebo
Other outcomes:
Locations:
Study officials:
References: