The Cohort network for Adolescents and youth with multipLe Mental health conditions (CALM) Master Observational Trial (MOT): study protocol

Youth seeking mental health services may present with complex, fluctuating symptom profiles, often meeting diagnostic criteria for multiple mental health conditions (MMHC). Otherwise referred to as mental health ‘multimorbidity,’ MMHC complicate clinical decision-making, predict poorer functional outcomes, and increase service utilization across the lifespan. Despite the prominence of MMHC, mental health research studies continue to primarily target single disorders. Master Observational Trial (MOT) designs can advance research in MMHC phenomenology and related interventions by providing a harmonized infrastructure for real-world clinical cohorts while embedding clinical trials. The Cohort network for Adolescents and youth with multipLe Mental health conditions (CALM) represents the first application, to our knowledge, of an MOT design in child and youth mental health. CALM is a multi-site, prospective longitudinal MOT enrolling youth aged 11–24 years into a harmonized “Light” ( n ~ 1,600) phenotyping protocol designed to simultaneously support intervention research. The CALM MOT is implemented across six sites in Canada. The Light protocol includes youth- and caregiver-reported measures capturing core clinical, functional, and contextual domains, alongside ‘point of care’ digital and biological data collection for genomic and proteomic analyses. Light data are captured at nine timepoints over 42 months. MMHC are assessed using the Diagnostic Assessment for the Health Spectrum, a research staff-administered semi–structured interview that yields Diagnostic and Statistical Manual of Mental Disorders-aligned categorical diagnoses and dimensional diagnostic spectra. A subset of Light protocol participants is enrolled into the Deep protocol ( n ~ 600), which includes expanded psychosocial, neurocognitive, and neuroimaging assessments collected over six months to enable mechanistic and translational analyses. The CALM MOT offers a unique opportunity to operationalise MMHC as a dynamic, multilevel prognostic construct, integrating diagnostic burden, developmental trajectories, and underlying mechanisms within a single study framework. The CALM MOT is actively recruiting and since its launch in March 2025, has enrolled 832 youth and 446 caregivers into the Light protocol, with 407 youth and 178 caregivers enrolled into the Deep protocol. Three randomized controlled trials addressing sleep, stigma, and youth with complex mental health needs are at varying stages of integration within the CALM MOT, leveraging the platform’s capacity to support embedded experimental research. NCT07699159.