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Shifting Brain Excitation-Inhibition Balance in Autism Spectrum Disorder

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ClinicalTrials.gov Identifier: NCT03537950
Recruitment Status : Unknown
Verified May 2018 by Dr Grainne McAlonan, King's College London.
Recruitment status was:  Active, not recruiting
First Posted : May 25, 2018
Last Update Posted : May 25, 2018
Sponsor:
Information provided by (Responsible Party):
Dr Grainne McAlonan, King's College London

Tracking Information
First Submitted Date  ICMJE April 17, 2018
First Posted Date  ICMJE May 25, 2018
Last Update Posted Date May 25, 2018
Actual Study Start Date  ICMJE August 22, 2016
Actual Primary Completion Date February 16, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2018)
Brain biochemistry response to pharmacological stimulation [ Time Frame: In the months 1-2 following the last day of scanning. ]
The measure of brain biochemistry response to PLC, CBD, and CBDV includes the following: Assessment of the ratio of brain excitation and inhibition (measured as the balance of excitatory and inhibitory neurotransmitters) using using proton magnetic resonance spectroscopy [1H]MRS.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2018)
  • Measurement of low frequency brain activity using resting state fMRI [ Time Frame: In the months 3-4 following the last day of scanning ]
    In the third and fourth month following the day of the last scan, we will measure whole brain low frequency brain activity using resting state functional magnetic resonance imaging. Measure of activity: fractional amplitude of low frequency fluctuations.
  • Measurement of brain functional connectivity using resting state fMRI [ Time Frame: In the months 5-6 following the last day of scanning ]
    In the fifth and sixth month following the day of the last scan, we will measure whole brain resting state functional connectivity using resting state functional magnetic resonance imaging. Measure of connectivity: correlation between pairs of regions.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Shifting Brain Excitation-Inhibition Balance in Autism Spectrum Disorder
Official Title  ICMJE Shifting Brain Excitation-Inhibition Balance Through the Endocannabinoid System in Men With Autism Spectrum Disorder (ASD) and in Healthy Controls
Brief Summary This study investigates brain response to single acute dose of cannabidiol, cannabidivarin, and placebo in healthy men with and without autism spectrum disorder
Detailed Description Previous research suggests that cannabidiol (CBD) and cannabidivarin (CBDV) could have the potential to shift brain excitation and inhibition (E-I) in the healthy brain and in neurodevelopmental psychiatric conditions, where this balance is disrupted, such as autism spectrum disorder (ASD). However, no study to date has investigated this. Therefore, in this study, we invited 20 healthy men with and without ASD. Each participant received each drug once (600mg CBD/CBDV, or matched placebo) and magnetic resonance imaging was used to obtain measures of brain biochemistry, activity, and connectivity. We further obtained questionnaires, task data, saliva, urine and blood samples, and conducted visual tasks using eye tracking, electroencephalography, and retinal imaging.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
Repeated-measures cross-over study, where each subject received each of three pharmacological probes once (order of drug administration was pseudorandomised)
Masking: Double (Participant, Investigator)
Masking Description:
Participants and investigators were blinded to the drug condition.
Primary Purpose: Basic Science
Condition  ICMJE Autism Spectrum Disorder
Intervention  ICMJE
  • Drug: PLC
    Single oral dose of PLC.
    Other Name: Placebo
  • Drug: CBD
    Single oral dose of cannabidiol (CBD) - 600mg.
    Other Name: Cannabidiol
  • Drug: CBDV
    Single oral dose of cannabidivarin (CBDV) - 600mg.
    Other Name: Cannabidivarin
Study Arms  ICMJE
  • Experimental: PLC, CBD, CBDV
    Dose order: PLC, CBD, CBDV
    Interventions:
    • Drug: PLC
    • Drug: CBD
    • Drug: CBDV
  • Experimental: PLC, CBDV, CBD
    Dose order: PL, CBDV, CBD
    Interventions:
    • Drug: PLC
    • Drug: CBD
    • Drug: CBDV
  • Experimental: CBD, PLC, CBDV
    Dose order: CBD, PLC, CBDV
    Interventions:
    • Drug: PLC
    • Drug: CBD
    • Drug: CBDV
  • Experimental: CBD, CBDV, PLC
    Dose order: CBD, CBDV, PLC
    Interventions:
    • Drug: PLC
    • Drug: CBD
    • Drug: CBDV
  • Experimental: CBDV, PLC, CBD
    Dose order: CBDV, PLC, CBD
    Interventions:
    • Drug: PLC
    • Drug: CBD
    • Drug: CBDV
  • Experimental: CBDV, CBD, PLC
    Dose order: CBDV, CBD, PLC
    Interventions:
    • Drug: PLC
    • Drug: CBD
    • Drug: CBDV
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: May 15, 2018)
38
Original Actual Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 27, 2019
Actual Primary Completion Date February 16, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • men
  • pass diagnostic threshold for ASD on the ADI-R (if informant is available)
  • currently symptomatic on ADOS
  • age 18-50 years
  • can give informed consent
  • IQ>70 (on a standard instrument such as WASI)
  • medication-free in the month preceding participation (but regular medication with drug, which does not affect glutamate or GABA directly may be permitted)
  • willing to provide urine samples to screen for use of illicit substances prior to each scan

Exclusion Criteria:

  • IQ<70
  • history of psychosis, co-morbid major mental illness, significant physical illness (heart disease, high blood pressure, seizures)
  • habitual substance misuse (including alcohol)
  • known allergy to cannabis
  • ASD caused by a known genetic syndrome e.g. Fragile X or 22q11 deletion syndrome,
  • past/present treatment for epilepsy
  • Women will be excluded from this pilot study to reduce heterogeneity in a small sample; avoid the issues around exposing women of reproductive age to a drug; and because pregnancy is a routine exclusion criteria for research MRI. Lastly, ASD is more common in men.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03537950
Other Study ID Numbers  ICMJE HR15-162744
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Dr Grainne McAlonan, King's College London
Study Sponsor  ICMJE King's College London
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Grainne McAlonan, PhD King's College London
PRS Account King's College London
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP