Cohort Network for Adolescents and Youth With multipLe Mental Health Conditions

Official title

Cohort Network for Adolescents and Youth With multipLe Mental Health Conditions (CALM): A Master Observational Trial

Overview

The Cohort Network for Adolescents and Youth With multipLe Mental Health Conditions (CALM) Master Observational Trial is a prospective, longitudinal observational study that seeks to improve clinical care for youth with multiple mental health conditions (MMHC), also known as mental health multimorbidity in the literature. MMHC is conceptualized as the presence of two or more mental health diagnoses under the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). MMHC is common in youth seeking mental health services and is associated with less favorable outcomes and greater health services utilization. Mental health disorders also accumulate in youth over time. The Master Observational Trial (MOT) will investigate MMHC in critical developmental periods in youth and identify risk and protective factors that will provide a mechanistic understanding of how MMHC develops over time. A subset of participants will also enroll in a Deep Phenotyping Cohort, which includes enhanced clinical and cognitive assessments and multimodal neuroimaging to investigate neurobiological mechanisms underlying MMHC and identify potential biomarkers of illness complexity and progression. In the near future, we aim to add to the current protocol to embed both a clinical trials network for youth mental health in Ontario and Calgary within the CALM study and add digital phenotyping using wearable technology to generate digital and physiological markers of MMHC. The current protocol focuses on establishing the longitudinal MOT cohort and Deep Phenotype Cohort only as a first step towards these long term CALM goals.

Detailed description

The primary objectives of the CALM MOT are to:

1. Establish a prospective, longitudinal cohort of children and youth aged 11-24 years to characterize the progression and outcomes of MMHC over time. 2. Facilitate later development of a clinical trials network and clinical research in MMHC with a focus on developing transdiagnostic interventions and improving care. 3. Establish a deeply phenotyped cohort of youth in a subset of participants enrolled in the MOT (light phenotyping protocol), using multidimensional, multilevel data to investigate brain-based mechanisms of MMHC with potential for biomarker discovery.

Specific objectives of the Deep Phenotyping Cohort are to:

1. Collect data across CALM sites in participants that are eligible and consent to participate in CALM MOT Light and the Deep Phenotyping Protocol. In this subset of CALM participants, we will extend the clinical/behavioural measurement battery, and collect high quality cognitive and multimodal (T1, multi-shell DWI, resting state, ASL) neuroimaging data that will be undertaken as part of the CALM baseline deep phenotyping protocol. 2. Use open access brain age and centile score calculators using unimodal brain imaging data to examine centile score distributions for various data samples in a sex stratified manner (e.g., clinical/community ascertained) and associations between centile scores with behavioral/cognitive indices of clinical severity/impairment and MMHC (e.g., MMHC index). Available open access normative and clinically enriched neuroimaging samples that overlap with the proposed CALM sample age range (11-24 years) will be utilized. 3. Undertake analysis using cross-sectional neuroimaging and longitudinal MOT data derived from the CALM network to test whether deviations from normative brain measures using either unimodal or integrating data from different imaging sequences (i.e., multimodal), imaging calculators may have utility as a baseline 'prognostic/predictive' marker of youth who may have more complex illness (i.e., MMHC) at the time of initial (baseline) participation in the CALM study and at subsequent time points and/or may be less responsive to clinical interventions.

Primary outcome measures

• Diagnostic Assessment for the Health Spectrum [Time frame: Baseline and 24 months]
• Adolescent Health History [Time frame: Baseline, 12 months, 24 months]
• Assessment of Quality of Life [Time frame: Baseline, 3 months, 6 months, 12 months, 18 months, 24 months]
• Brain-CODE Demographic Form [Time frame: Baseline, 12 months, 24 months]
• Brain-CODE Medical History Form incorporating Developmental History Questionnaire (DHQ) Items [Time frame: Baseline, 12 months, 24 months]
• Canadian Health Survey on Children and Youth (CHSCY) Childhood Experiences Scale [Time frame: Baseline, 12 months, 24 months]
• Child and Youth Resilience Measure [Time frame: Baseline, 12 months, 24 months, 36 months]
• The Columbia Suicide Severity Rating Scale [Time frame: Baseline, 24 months]
• Self-Injurious Thoughts and Behaviours Interview [Time frame: Baseline, 24 months]
• Canadian Health Survey on Children and Youth (CHSCY) Bullying Scale [Time frame: Baseline, 12 months, 24 months]

Eligibility criteria

Inclusion criteria

The participant must meet all of the inclusion criteria to be eligible for this research study:

• Light Phenotype Eligibility Must sign and date the informed consent form, or provide assent and have a Substitute Decision Maker provide informed consent; Aged 11-24 years old at the time of screening; Any person within age criteria who has previously sought, is seeking, or is accessing mental health services; Are able to complete assessments in English.

Deep Phenotype Eligibility Must be part of the CALM light phenotype cohort; Must sign and date the deep phenotyping informed consent form, or provide assent and have a Substitute Decision Maker provide informed consent.

Light Phenotype Caregiver Participant Eligibility:

Any caregiver of a CALM child/youth participant is eligible to participate in the study, insofar as the child/youth participant has consented to the light phenotype cohort and has agreed for their caregiver to be contacted to participate in the study; Must sign and date the informed consent form.

Deep Phenotype Caregiver Participant Eligibility:

Any caregiver of a CALM child/youth participant is eligible to participate in the study, insofar as the child/youth participant has consented to the deep phenotype cohort and has agreed for their caregiver to be contacted to participate in the study; Must sign and date the informed consent form.

Exclusion criteria

An individual who meets any of the following criteria will be excluded from participation in this research study:

Light Phenotype Does not provide informed consent (for those with the capacity to consent) or assent (for those who lack the capacity to consent); For those individuals who lack the capacity to consent, the inability of the parent/legal guardian to provide informed consent for the youth is also an exclusion criterion; Those who lack capacity to consent include individuals who are non-verbal or unable to speak any English.

Deep Phenotype Unable to participate in deep phenotyping protocol (e.g., MRI contraindication, uncorrected vision or hearing impairments that would interfere with data collection, unwillingness to complete assessments); No exclusion criteria are based on race, ethnicity, sex or gender.

Light Phenotype Caregiver Participant Ineligibility:

Caregivers of CALM child/youth participants are ineligible to participate in the study if:

The child/youth participant does not agree for their caregiver to be contacted to participate in the study; The child/youth participant is not participating in the light phenotype cohort; Does not provide informed consent (for those with the capacity to consent). Those who lack capacity to consent include individuals who are non-verbal or unable to speak any English.

Deep Phenotype Caregiver Participant Ineligibility:

Caregivers of CALM child/youth participants are ineligible to participate in the study if:

The child/youth participant does not agree for their caregiver to be contacted to participate in the study; The child/youth participant is not participating in the deep phenotype cohort (i.e., is only participating in the light phenotyping cohort); Does not provide informed consent (for those with the capacity to consent). Those who lack capacity to consent include individuals who are non-verbal or unable to speak any English.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Canada · 6 centers

• University of Calgary — Calgary
• McMaster Children's Hospital, Hamilton Health Sciences — Hamilton
• Children's Hospital of Eastern Ontario Research Institute — Ottawa
• The Royal Ottawa Mental Health Centre — Ottawa
• The Hospital for Sick Children — Toronto
• Centre for Addiction and Mental Health (CAMH) — Toronto

Publications

• Zabihi M, Floris DL, Kia SM, Wolfers T, Tillmann J, Arenas AL, Moessnang C, Banaschewski T, Holt R, Baron-Cohen S, Loth E, Charman T, Bourgeron T, Murphy D, Ecker C, Buitelaar JK, Beckmann CF, Marquand A; EU-AIMS LEAP Group. Fractionating autism based on neuroanatomical normative modeling. Transl Psychiatry. 2020 Nov 6;10(1):384. doi: 10.1038/s41398-020-01057-0. PMID 33159037
• Youngstrom EA, Frazier TW, Demeter C, Calabrese JR, Findling RL. Developing a 10-item mania scale from the Parent General Behavior Inventory for children and adolescents. J Clin Psychiatry. 2008 May;69(5):831-9. doi: 10.4088/jcp.v69n0517. PMID 18452343
• Young, K. S. (1998). Internet Addiction: The Emergence of a New Clinical Disorder. CyberPsychology & Behavior, 1(3), 237-244. https://doi.org/10.1089/cpb.1998.1.237
• Wood DL, Sawicki GS, Miller MD, Smotherman C, Lukens-Bull K, Livingood WC, Ferris M, Kraemer DF. The Transition Readiness Assessment Questionnaire (TRAQ): its factor structure, reliability, and validity. Acad Pediatr. 2014 Jul-Aug;14(4):415-22. doi: 10.1016/j.acap.2014.03.008. PMID 24976354
• Wolfers T, Rokicki J, Alnaes D, Berthet P, Agartz I, Kia SM, Kaufmann T, Zabihi M, Moberget T, Melle I, Beckmann CF, Andreassen OA, Marquand AF, Westlye LT. Replicating extensive brain structural heterogeneity in individuals with schizophrenia and bipolar disorder. Hum Brain Mapp. 2021 Jun 1;42(8):2546-2555. doi: 10.1002/hbm.25386. Epub 2021 Feb 27. PMID 33638594
• Wolfers T, Beckmann CF, Hoogman M, Buitelaar JK, Franke B, Marquand AF. Individual differences v. the average patient: mapping the heterogeneity in ADHD using normative models. Psychol Med. 2020 Jan;50(2):314-323. doi: 10.1017/S0033291719000084. Epub 2019 Feb 14. PMID 30782224
• Wechsler Intelligence Scale for Children | Fifth Edition. (n.d.). Retrieved April 17, 2024, from https://www.pearsonassessments.com/store/usassessments/en/Store/Professional-Assessments/Cognition-%26-Neuro/Wechsler-Intelligence-Scale-for-Children-%7C-Fifth-Edition-/p/100000771.html
• Veale JF. Edinburgh Handedness Inventory - Short Form: a revised version based on confirmatory factor analysis. Laterality. 2014;19(2):164-77. doi: 10.1080/1357650X.2013.783045. Epub 2013 May 10. PMID 23659650

Identifiers

NCT: NCT07699159 · 4792

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗