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Genetic Counselling in the Prevention of Mental Health Consequences of Cannabis Use (IMAGINE)

Primary Purpose

Mental Illness, Schizophrenia, Bipolar Disorder

Status
Recruiting
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Genetic counselling
Sponsored by
Nova Scotia Health Authority
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Mental Illness focused on measuring Severe mental illness, Developmental psychopathology, Trial-within-cohort, Genetic counselling, Cannabis use, Prevention

Eligibility Criteria

12 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Enrolment in the Families Overcoming Risks and Building Opportunities for Well-being (FORBOW) study.
  • Age between 12 and 21 years.
  • Knowledge of English sufficient to benefit from the intervention.
  • Capacity to provide informed consent at most recent FORBOW assessment.
  • Provision of consent to be contacted about future studies at most recent FORBOW assessment.

Exclusion Criteria:

  • A diagnosis of severe mental illness (psychotic disorder, bipolar disorder, severe/recurrent depression) at baseline
  • Autism or intellectual disability of a degree that interferes with assessment (IQ < 70)

Sites / Locations

  • Nova Scotia Health AuthorityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Genetic counselling

Control group

Arm Description

Eligible participants who are randomized will be contacted and offered an invitation to attend the intervention. Genetic counselling will be provided to participants who accept the intervention as a single 1-2 hour session by a board-certified genetic counsellor. During the genetic counselling session, participants will have the option to receive their genotype at rs2494732. Participants will be counselled regarding their individualized risk of developing and of NOT developing SMI based on family history, whether or not they choose to use cannabis, and genotype (if they accept the genetic test results). Approximately 1 month after the intervention, participants will receive a follow-up interview.

Eligible participants who are not randomized to be offered the intervention will continue with their annual assessments as part of the parent study. These participants will receive the current standard of care (no intervention), and will not be offered or informed of the intervention.

Outcomes

Primary Outcome Measures

Self-reported cannabis use
Self-reported cannabis use on a questionnaire.

Secondary Outcome Measures

The proportion of participants who complete the intervention after receiving an offer to participate (intervention acceptability)
Acceptability will be established as the proportion of individuals accepting the offer of intervention.
Presence of cannabinoids in urine
Urine will be screened for the presence/absence of cannabinoids.

Full Information

First Posted
July 5, 2018
Last Updated
February 6, 2023
Sponsor
Nova Scotia Health Authority
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1. Study Identification

Unique Protocol Identification Number
NCT03601026
Brief Title
Genetic Counselling in the Prevention of Mental Health Consequences of Cannabis Use
Acronym
IMAGINE
Official Title
Interdisciplinary Approach to Maximize Adolescent Potential: Genetic Counselling Interventions to Reduce Negative Environmental Effects
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2019 (Actual)
Primary Completion Date
September 1, 2024 (Anticipated)
Study Completion Date
September 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Nova Scotia Health Authority

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Severe mental illness (SMI) refers to the most burdensome psychiatric conditions. The need to pre-empt the onset of SMI is pressing because once SMI develops, quality of life is poor and available treatments have limited efficacy. Most risk factors for SMI are either unchangeable (e.g., genetics) or difficult to alter (e.g., low socio-economic status). In contrast, cannabis use is one specific risk factor that could be avoided. Certain individuals are more vulnerable to the harmful effects of cannabis. Genetic factors can help us identify these high-risk individuals. One in three individuals are carriers of a higher-risk genetic variant, and cannabis users with this genotype are at up to 7-fold increased risk of developing schizophrenia. In our study, genetic counselling will be provided to participants by a board-certified genetic counsellor. During the genetic counselling session, participants will have the option to receive their genotype. Participants will be counselled regarding their individualized risk of developing and of not developing SMI based on family history, whether or not they choose to use cannabis, and genotype (if the participants accept the genetic test results). The investigators hypothesize that this intervention will reduce exposure to cannabis compared to the youth who are not offered the intervention.
Detailed Description
Severe mental illness (SMI) refers to the most burdensome forms of psychiatric disorder, including schizophrenia, bipolar disorder, and severe depression. These illnesses typically emerge in adolescence or young adulthood and are associated with substantial impairment in functioning. A significant proportion (~30%) of individuals with SMI remain resistant to any form of available pharmacotherapy. The combination of early onset, poor response to treatment and persistent disability makes SMI the most problematic group of illnesses to individuals and society. The need for early interventions to pre-empt the onset of SMI is pressing because once SMI develops, quality of life is poor for patients and their families. There is substantial overlap in the genetic and environmental risk factors for individual forms of SMI, and predictors of SMI are not specific to any one disorder. It is therefore necessary to conceptualize SMI as transdiagnostic and include diagnoses of schizophrenia, bipolar disorder, and depression, rather than focusing on single illnesses when developing preventative interventions. Prevention of SMI is currently hindered by the inability to identify those at risk early enough to normalize their developmental trajectory. Recent advances in genomics and the understanding of important gene-environment interactions may help overcome this challenge and enable effective and targeted prevention of SMI. Cannabis exposure during critical periods of brain maturation is an avoidable environmental risk factor for SMI. A replicated gene-cannabis interaction shows that carriers of a common genetic variant (C alleles at rs2494732 in the AKT1 gene) are at up to 7-fold increased risk of developing psychosis if they use cannabis. Genetic counselling provides a powerful tool to communicate genetic information to youth in a way that empowers and enhances health. The present project involves the delivery of a genetic counselling intervention to inform youth of their personalized risk of developing SMI based on genotype, family history, and whether or not they choose to use cannabis. This project will be the first application of molecular genetic information and genetic counselling to prevent SMI. Aim: To test if genetic counselling regarding personalized risk information based on a replicated gene-cannabis interaction reduces cannabis use in youth at high risk of developing severe mental illness. Hypotheses: A genetic counselling intervention will be acceptable to youth at high familial risk of SMI. A genetic counselling intervention with personalized feedback of AKT1 genotype will reduce cannabis use among vulnerable youth. The effect of the intervention will be moderated by AKT1 genotype, with greater reduction of cannabis use among carriers of the sensitive C alleles. Method: A cohort of over 450 youth (aged 3-29) has been enrolled as part of the Families Overcoming Risks and Building Opportunities for Well-being (FORBOW) study. The investigators have obtained biological samples for measurement of genetic variation and the investigators will obtain biological samples to measure cannabis exposure. The investigators will randomly select one in every two eligible youth (aged 12-21) to be offered genetic counselling during which the participants will be provided with personalized genetic information and they will be counselled regarding risk of developing SMI based on genotype, family history, and whether or not they choose to use cannabis. The investigators will follow the participants through the developmental period with the highest risk of cannabis use initiation and the investigators will assess cannabis use and psychopathology annually. The primary outcome will be abstinence from cannabis reported by participants in confidential interviews and confirmed by measurement of the primary metabolites of psychoactive Δ9-tetrahydrocannabinol in blood and urine samples. Significance: This project will realize the first translational application of a gene-environment interaction to improve mental health and test an intervention with potential public health benefits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mental Illness, Schizophrenia, Bipolar Disorder, Major Depressive Disorder, Cannabis Use, Psychosis
Keywords
Severe mental illness, Developmental psychopathology, Trial-within-cohort, Genetic counselling, Cannabis use, Prevention

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Trial-within-cohort
Masking
Outcomes Assessor
Masking Description
Eligible participants who are randomized to not be offered the intervention will not be aware of the presence of a potential intervention. Study staff who are assessing outcomes (i.e., psychopathology, cannabis use) will not know who did and did not receive the intervention.
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Genetic counselling
Arm Type
Experimental
Arm Description
Eligible participants who are randomized will be contacted and offered an invitation to attend the intervention. Genetic counselling will be provided to participants who accept the intervention as a single 1-2 hour session by a board-certified genetic counsellor. During the genetic counselling session, participants will have the option to receive their genotype at rs2494732. Participants will be counselled regarding their individualized risk of developing and of NOT developing SMI based on family history, whether or not they choose to use cannabis, and genotype (if they accept the genetic test results). Approximately 1 month after the intervention, participants will receive a follow-up interview.
Arm Title
Control group
Arm Type
No Intervention
Arm Description
Eligible participants who are not randomized to be offered the intervention will continue with their annual assessments as part of the parent study. These participants will receive the current standard of care (no intervention), and will not be offered or informed of the intervention.
Intervention Type
Behavioral
Intervention Name(s)
Genetic counselling
Intervention Description
Participants will receive information on risk/protective factors and causes of mental illness. Participants are not required to receive numeric/genetic risk information. Participants who choose to receive genetic and/or numeric risk information will be counselled on their risk of NOT developing and of developing SMI based on their genetic test results and/or family history information they provide. Risk estimates will be derived by genetic counsellors, according to standard practice guidelines. Participants who receive genetic information will be counselled on the possible influence of cannabis use on risk of mental illness based on their genotype. Participants who choose to not receive genetic information will be counselled on the influence of cannabis on mental health.
Primary Outcome Measure Information:
Title
Self-reported cannabis use
Description
Self-reported cannabis use on a questionnaire.
Time Frame
1 month
Secondary Outcome Measure Information:
Title
The proportion of participants who complete the intervention after receiving an offer to participate (intervention acceptability)
Description
Acceptability will be established as the proportion of individuals accepting the offer of intervention.
Time Frame
Completion of study (2 years).
Title
Presence of cannabinoids in urine
Description
Urine will be screened for the presence/absence of cannabinoids.
Time Frame
1 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Enrolment in the Families Overcoming Risks and Building Opportunities for Well-being (FORBOW) study. Age between 12 and 21 years. Knowledge of English sufficient to benefit from the intervention. Capacity to provide informed consent at most recent FORBOW assessment. Provision of consent to be contacted about future studies at most recent FORBOW assessment. Exclusion Criteria: A diagnosis of severe mental illness (psychotic disorder, bipolar disorder, severe/recurrent depression) at baseline Autism or intellectual disability of a degree that interferes with assessment (IQ < 70)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rudolf Uher, MD, PhD
Phone
902-473-7209
Email
uher@dal.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Jill M Cumby, RN, MN
Phone
902-473-1781
Email
Jill.Cumby@nshealth.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rudolf Uher, MD, PhD
Organizational Affiliation
Nova Scotia Health Authority, Dalhousie University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nova Scotia Health Authority
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 2E2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rudolf Uher, MD PhD
Email
uher@dal.ca
First Name & Middle Initial & Last Name & Degree
Jill Cumby, RN
Email
jill.cumby@nshealth.ca

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33242924
Citation
Zwicker A, LeBlanc MA, Pavlova B, Alda M, Denovan-Wright EM, Uher R, Austin JC. Genetic counselling for the prevention of mental health consequences of cannabis use: A randomized controlled trial-within-cohort. Early Interv Psychiatry. 2021 Oct;15(5):1306-1314. doi: 10.1111/eip.13082. Epub 2020 Nov 26.
Results Reference
derived
Links:
URL
http://www.forbow.org
Description
FORBOW study website.

Learn more about this trial

Genetic Counselling in the Prevention of Mental Health Consequences of Cannabis Use

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