Accelerated Neuromodulation Therapy and Neurocomputational Biomarkers in Individuals at Clinical High Risk for Psychosis (TMS-CHR)
The goal of this study is to learn whether an accelerated form of neuromodulation therapy is safe, feasible, and well tolerated in young people at clinical high risk for psychosis (CHR-P), and whether it is associated with changes in candidate biomarkers of treatment response.
Participants will be randomly assigned to receive either active accelerated intermittent theta burst stimulation (iTBS) or sham stimulation to the left dorsolateral prefrontal cortex, delivered over five consecutive days.
The study will look at whether this accelerated treatment approach is safe and feasible for people at clinical high risk for psychosis, whether depressive symptoms improve after treatment, and whether computerized behavioural tasks and passive digital monitoring (wearables, smartphone apps, and speech analysis) can detect treatment-related changes that may serve as biomarkers for future, larger trials.
Participants will complete clinical interviews and questionnaires, a cognitive battery, and computerized behavioral tasks; wear a Fitbit and use smartphone applications for at least two weeks before and throughout treatment; receive neuromodulation therapy or sham stimulation over five consecutive days; and attend follow-up visits at 1 week, 1 month, and 3 months after treatment.
Descripción general del estudio
Estado
Descripción detallada
There is currently no clinically validated treatment that reduces the risk of psychosis onset or mitigates the severity of a first psychotic episode in individuals at clinical high risk for psychosis (CHR-P). CHR-P is associated with attenuated psychotic symptoms, functional decline, and high rates of affective symptoms, including a comorbid mood disorder prevalence of 40% or higher. Repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (LDLPFC) is an established treatment for depression and is increasingly supported for negative symptoms in psychotic disorders, making it a promising low-burden candidate for early intervention in CHR-P.
This pilot study evaluates an accelerated intermittent theta burst stimulation (iTBS) protocol, delivered over five consecutive days, in individuals at CHR-P (SIPS-confirmed, aged 18-34). Forty participants will be randomized 1:1 to active accelerated iTBS or sham stimulation to the LDLPFC, using standard scalp-based (BEAM-F3) targeting rather than MRI-guided neuronavigation, reflecting the pilot nature and funding constraints of this early-phase study.
Given the variable incidence of and long latency to psychosis onset in the CHR-P population, this study also incorporates a battery of neurocomputational tasks (analyzed using Hierarchical Gaussian Filter modeling) and a multimodal digital phenotyping framework (wearables, smartphone-based passive sensing, facial/vocal affect analysis, and structured speech analysis) to assess candidate biomarkers of treatment response.
Primary outcomes are the safety, feasibility, and tolerability of the accelerated protocol in this population. Secondary outcomes include the sensitivity of neurocomputational biomarkers to treatment and change in depressive symptoms. Exploratory outcomes include treatment-related change across multiple domains of real-world functioning captured through digital phenotyping. This study is not designed to establish definitive treatment efficacy but to inform the design of future, adequately powered trials.
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Ashley Choucroun
- Número de teléfono: 5146593488
- Correo electrónico: ashley.choucroun.comtl@ssss.gouv.qc.ca
Ubicaciones de estudio
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Quebec
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Verdun, Quebec, Canadá, H4H1R3
- Reclutamiento
- McGill Lab for Computational Psychiatry and Translation
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Contacto:
- Ashley Choucroun
- Número de teléfono: 5146593488
- Correo electrónico: ashley.choucroun.comtl@ssss.gouv.qc.ca
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Investigador principal:
- David Benrimoh
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- Meets clinical CHR-P criteria, confirmed by the Structured Interview for Psychosis-Risk Syndromes (SIPS)
- Clinical team confirms sufficient stability to participate
- Able to provide informed consent
Exclusion Criteria:
- Pregnancy, lactation, or intrauterine device
- History of electroconvulsive therapy (ECT) in the past 6 months
- Substance use during the treatment week (cigarettes and cannabis excluded from this consideration)
- Contraindications for TMS (e.g., metal implants in head/neck, seizure history, brain tumor/neurosurgery, severe cardiac disease)
- Previous rTMS treatment
- Documented history of significant intellectual disability
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Triple
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Active iTBS (BEAM-F3 Targeting)
Participants receive active accelerated iTBS over five consecutive days (up to 10 sessions/day, up to 50 sessions total) targeting the left dorsolateral prefrontal cortex (LDLPFC) using standard BEAM-F3 scalp-based coordinates.
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Active iTBS is delivered using a MagVenture MagPro X100 stimulator with Cool-B65 A/P coil, targeting the LDLPFC at 110% of resting motor threshold (motor threshold determined via the PEST algorithm).
Each session consists of 60 trains of 10 bursts of three pulses at 50 Hz, delivered every 200 ms, with an 8-second intertrain interval (1,800 pulses/session; up to 18,000 pulses/day; 90,000 pulses total over 5 days).
The number of daily sessions is reviewed after every five participants and may be reduced from 10 to 8, or to 6, if needed; missed sessions are made up during the following week to preserve total pulse dose.
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Comparador falso: Sham iTBS
Participants receive sham stimulation over five consecutive days, using the same device, coil, session structure, and schedule as the active arm, without delivering therapeutic cortical stimulation.
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Sham iTBS is delivered using the same MagVenture Cool B65 A/P coil (device-integrated sham mode), with identical coil placement, session structure, and treatment schedule as the active arm.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Treatment Initiation Rate
Periodo de tiempo: Through end of treatment week (Day 5)
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Proportion of consenting participants who begin the treatment protocol (receive at least one stimulation session).
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Through end of treatment week (Day 5)
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Treatment Acceptability Rate
Periodo de tiempo: Through study completion, an average of 18 months.
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Proportion of approached, eligible individuals who consent to participate in the study.
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Through study completion, an average of 18 months.
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Treatment Adherence
Periodo de tiempo: Through end of treatment week (Day 5)
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Number of treatment sessions completed per participant, out of the planned schedule (up to 10 sessions/day over 5 days).
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Through end of treatment week (Day 5)
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Treatment Completion Rate
Periodo de tiempo: Through end of treatment week (Day 5)
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Proportion of participants who initiate treatment and complete the full course; expected completion rate of approximately 80%, based on prior work at the study site.
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Through end of treatment week (Day 5)
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Incidence of Adverse and Serious Adverse Events
Periodo de tiempo: Baseline through 3-month follow-up
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Rate of treatment-related adverse events (e.g., scalp pain, headache, fatigue, symptom worsening) and serious adverse events (e.g., seizure, hospitalization, emergent suicidality), assessed via daily clinical ratings and structured interviews.
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Baseline through 3-month follow-up
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Qualitative Treatment Experience
Periodo de tiempo: End of treatment (Day 5)
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Themes related to participant experience of tolerability and treatment burden, derived from a structured end-of-treatment qualitative interview and analyzed using inductive thematic analysis.
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End of treatment (Day 5)
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change in Affective Conditioned Hallucinations Task Parameters
Periodo de tiempo: Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in individual-level information-processing parameters (Hierarchical Gaussian Filter modeling) derived from an affective variant of the Conditioned Hallucinations task.
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Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in Social Appraisal Task Parameters
Periodo de tiempo: Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in HGF-derived parameters of social inference and belief updating.
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Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in Beads Task Parameters
Periodo de tiempo: Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in probabilistic reasoning bias related to delusion-proneness.
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Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in Prisoner's Dilemma Task Parameters
Periodo de tiempo: Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in HGF-derived parameters of social inference.
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Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Score
Periodo de tiempo: Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in clinician-rated depressive symptom severity.
Total scores range from 0 to 60, with higher scores indicating greater severity.
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Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in Quick Inventory of Depressive Symptomatology (QIDS) Score
Periodo de tiempo: Baseline, Daily from Day 1 to Day 5, and at 1 week, 1 month, and 3 months post-treatment
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Change in self-reported depressive symptom severity on the Quick Inventory of Depressive Symptomatology, 16-item Self-Report (QIDS-SR16).
Total scores range from 0 to 27, with higher scores indicating greater depressive symptom severity.
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Baseline, Daily from Day 1 to Day 5, and at 1 week, 1 month, and 3 months post-treatment
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change in Heart Rate During Task Performance
Periodo de tiempo: Baseline to 1 week, 1 month, and 3 months post-treatment
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Heart rate recorded via BIOPAC physiological monitoring during the computational task battery, measured in beats per minute (bpm).
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Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in Galvanic Skin Response During Task Performance
Periodo de tiempo: Baseline to 1 week, 1 month, and 3 months post-treatment
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Galvanic skin response (electrodermal activity) recorded via BIOPAC physiological monitoring during the computational task battery, measured in microsiemens (µS).
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Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in Sleep Consolidation
Periodo de tiempo: Continuous, from 2-week baseline lead-in through 3-month follow-up
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Sleep consolidation (e.g., sleep efficiency, wake after sleep onset) recorded via Fitbit wearable device.
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Continuous, from 2-week baseline lead-in through 3-month follow-up
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Change in Daytime Activity Level
Periodo de tiempo: Continuous, from 2-week baseline lead-in through 3-month follow-up
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Daytime activity level (e.g., step count) recorded via Fitbit wearable device.
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Continuous, from 2-week baseline lead-in through 3-month follow-up
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Change in Geolocation-Based Mobility
Periodo de tiempo: Continuous, from 2-week baseline lead-in through 3-month follow-up
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Geolocation-based mobility patterns (e.g., time spent away from home, location variability) recorded via mindLAMP passive sensing.
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Continuous, from 2-week baseline lead-in through 3-month follow-up
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Change in Phone Usage Patterns
Periodo de tiempo: Continuous, from 2-week baseline lead-in through 3-month follow-up
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Smartphone usage patterns (e.g., screen time, app engagement) recorded via mindLAMP passive sensing.
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Continuous, from 2-week baseline lead-in through 3-month follow-up
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Change in Facial Expressivity
Periodo de tiempo: Continuous, from 2-week baseline lead-in through 3-month follow-up
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Facial expressivity recorded via the EMOCARE application using automated facial action unit analysis.
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Continuous, from 2-week baseline lead-in through 3-month follow-up
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Change in Vocal Prosody
Periodo de tiempo: Continuous, from 2-week baseline lead-in through 3-month follow-up
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Vocal prosody (e.g., pitch variability, speech rate) recorded via the EMOCARE application.
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Continuous, from 2-week baseline lead-in through 3-month follow-up
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Change in Speech Coherence
Periodo de tiempo: Baseline to 1 week, 1 month, and 3 months post-treatment
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Linguistic coherence features (e.g., semantic coherence) extracted from structured speech samples (Quebec Speech Bank), associated with thought disorder.
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Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in Speech Prosody
Periodo de tiempo: Baseline to 1 week, 1 month, and 3 months post-treatment
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Prosodic features (e.g., pitch, pause duration) extracted from structured speech samples (Quebec Speech Bank), associated with negative symptoms.
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Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in Structured Interview for Psychosis-Risk Syndromes (SIPS) Positive Symptom Score
Periodo de tiempo: Baseline to 1 week, 1 month, and 3 months post-treatment
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Sum of the 5 SIPS positive symptom severity items (P1-P5), each rated 0-6.
Total scores range from 0 to 30, with higher scores indicating greater positive symptom severity.
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Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in Scale for the Assessment of Negative Symptoms (SANS) Total Score
Periodo de tiempo: Baseline to 1 week, 1 month, and 3 months post-treatment
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Sum of the 4 global rating items across the Affective Flattening or Blunting, Alogia, Avolition-Apathy, and Anhedonia-Asociality subscales, each rated 0-5.
Total scores range from 0 to 20, with higher scores indicating greater negative symptom severity.
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Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in Scale for the Assessment of Positive Symptoms (SAPS) Score
Periodo de tiempo: Baseline to 1 week, 1 month, and 3 months post-treatment
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Sum of the 4 global rating items across the Hallucinations, Delusions, Bizarre Behavior, and Positive Formal Thought Disorder subscales, each rated 0-5.
Total scores range from 0 to 20, with higher scores indicating greater positive symptom severity.
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Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in Positive and Negative Syndrome Scale (PANSS) Total Score
Periodo de tiempo: Baseline to 1 week, 1 month, and 3 months post-treatment
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Total scores range from 30 to 210, with higher scores indicating greater overall symptom severity.
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Baseline to 1 week, 1 month, and 3 months post-treatment
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Change in Social and Occupational Functioning Assessment Scale (SOFAS) Score
Periodo de tiempo: Baseline to 1 week, 1 month, and 3 months post-treatment
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Scores range from 0 to 100, with higher scores indicating better functioning.
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Baseline to 1 week, 1 month, and 3 months post-treatment
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: David Benrimoh, McGill University, Department of Psychiatry
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
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Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 2026-1387
Plan de datos de participantes individuales (IPD)
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Información sobre medicamentos y dispositivos, documentos del estudio
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