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.
Přehled studie
Postavení
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Fáze
- Nelze použít
Kontakty a umístění
Studijní kontakt
- Jméno: Ashley Choucroun
- Telefonní číslo: 5146593488
- E-mail: ashley.choucroun.comtl@ssss.gouv.qc.ca
Studijní místa
-
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Quebec
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Verdun, Quebec, Kanada, H4H1R3
- Nábor
- McGill Lab for Computational Psychiatry and Translation
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Kontakt:
- Ashley Choucroun
- Telefonní číslo: 5146593488
- E-mail: ashley.choucroun.comtl@ssss.gouv.qc.ca
-
Vrchní vyšetřovatel:
- David Benrimoh
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
Přijímá zdravé dobrovolníky
Popis
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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Trojnásobný
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: 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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Falešný srovnávač: 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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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Treatment Initiation Rate
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Change in Affective Conditioned Hallucinations Task Parameters
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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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Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Change in Heart Rate During Task Performance
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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.
|
Baseline to 1 week, 1 month, and 3 months post-treatment
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Spolupracovníci a vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: David Benrimoh, McGill University, Department of Psychiatry
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
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První zveřejněno (Aktuální)
Aktualizace studijních záznamů
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Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
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