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Shifting Brain Excitation-Inhibition Balance in Autism Spectrum Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03537950
Recruitment Status : 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

Study Description
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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

Condition or disease Intervention/treatment Phase
Autism Spectrum Disorder Drug: PLC Drug: CBD Drug: CBDV Not Applicable

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
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
Official Title: Shifting Brain Excitation-Inhibition Balance Through the Endocannabinoid System in Men With Autism Spectrum Disorder (ASD) and in Healthy Controls
Actual Study Start Date : August 22, 2016
Actual Primary Completion Date : February 16, 2017
Estimated Study Completion Date : April 27, 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: PLC, CBD, CBDV
Dose order: PLC, CBD, CBDV
 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
Experimental: PLC, CBDV, CBD
Dose order: PL, CBDV, CBD
 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
Experimental: CBD, PLC, CBDV
Dose order: CBD, PLC, CBDV
 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
Experimental: CBD, CBDV, PLC
Dose order: CBD, CBDV, PLC
 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
Experimental: CBDV, PLC, CBD
Dose order: CBDV, PLC, CBD
 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
Experimental: CBDV, CBD, PLC
Dose order: CBDV, CBD, PLC
 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


Outcome Measures
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Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. 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.

  2. 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.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03537950


Locations
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United Kingdom
King's College London
London, United Kingdom, SE5 8AF
Sponsors and Collaborators
King's College London
Investigators
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Principal Investigator: Grainne McAlonan, PhD King's College London
More Information
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Responsible Party: Dr Grainne McAlonan, Deputy head of department, King's College London
ClinicalTrials.gov Identifier: NCT03537950    
Other Study ID Numbers: HR15-162744
First Posted: May 25, 2018    Key Record Dates
Last Update Posted: May 25, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dr Grainne McAlonan, King's College London:
Cannabidiol
Cannabidivarin
E-I balance
pharmacological imaging
Additional relevant MeSH terms:
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Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
 Mental Disorders
Epidiolex
Anticonvulsants