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

Schizophrenia Clinical Trial

— IMAGINE  

Official title:

Interdisciplinary Approach to Maximize Adolescent Potential: Genetic Counselling Interventions to Reduce Negative Environmental Effects

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03601026
• Other study ID #: IMGN18
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2019
• Est. completion date: September 1, 2024

Study information

• Verified date: February 2023
• Source: Nova Scotia Health Authority
• Contact: Rudolf Uher, MD, PhD
• Phone: 902-473-7209
• Email: uher[@]dal.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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: 1. A genetic counselling intervention will be acceptable to youth at high familial risk of SMI. 2. A genetic counselling intervention with personalized feedback of AKT1 genotype will reduce cannabis use among vulnerable youth. 3. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: September 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 21 Years

Eligibility

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)

Related Conditions & MeSH terms

• Bipolar Disorder
• Cannabis Use
• Depressive Disorder
• Depressive Disorder, Major
• Disease
• Major Depressive Disorder
• Marijuana Abuse
• Mental Disorders
• Mental Illness
• Psychosis
• Schizophrenia

Intervention

Behavioral:
• Genetic counselling
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.

Locations

Country	Name	City	State
Canada	Nova Scotia Health Authority	Halifax	Nova Scotia

Sponsors (1)

Lead Sponsor	Collaborator
Nova Scotia Health Authority

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Self-reported cannabis use	Self-reported cannabis use on a questionnaire.	1 month
Secondary	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.	Completion of study (2 years).
Secondary	Presence of cannabinoids in urine	Urine will be screened for the presence/absence of cannabinoids.	1 month

External Links

•   FORBOW study website.