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NCT Number: NCT07786714

Accelerated Neuromodulation Therapy and Neurocomputational Biomarkers in Individuals at Clinical High Risk for Psychosis

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.

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Key information

Conditions

Clinical High Risk for Psychosis (CHR) Mental Disorders Pathological Conditions, Signs and Symptoms Prodromal Symptoms Psychotic Disorders Schizophrenia Spectrum and Other Psychotic Disorders Signs and Symptoms

Age range

18 year–34 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

McGill Lab for Computational Psychiatry and Translation

Verdun, Quebec, H4H1R3, Canada

Location status: Recruiting

Location contact

Ashley Choucroun

CONTACT

[email protected]

5146593488

David Benrimoh

PRINCIPAL_INVESTIGATOR

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Active Intermittent Theta Burst Stimulation (BEAM-F3 Targeting)

Device

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.

Sham Comparator: Sham iTBS

Device

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.

Primary outcomes

  1. Treatment Initiation Rate

    Time frame: Through end of treatment week (Day 5)

    Proportion of consenting participants who begin the treatment protocol (receive at least one stimulation session).

  2. Treatment Acceptability Rate

    Time frame: Through study completion, an average of 18 months.

    Proportion of approached, eligible individuals who consent to participate in the study.

  3. Treatment Adherence

    Time frame: Through end of treatment week (Day 5)

    Number of treatment sessions completed per participant, out of the planned schedule (up to 10 sessions/day over 5 days).

  4. Treatment Completion Rate

    Time frame: Through end of treatment week (Day 5)

    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.

  5. Incidence of Adverse and Serious Adverse Events

    Time frame: Baseline through 3-month follow-up

    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.

  6. Qualitative Treatment Experience

    Time frame: End of treatment (Day 5)

    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.

Secondary outcomes

  1. Change in Affective Conditioned Hallucinations Task Parameters

    Time frame: Baseline to 1 week, 1 month, and 3 months post-treatment

    Change in individual-level information-processing parameters (Hierarchical Gaussian Filter modeling) derived from an affective variant of the Conditioned Hallucinations task.

  2. Change in Social Appraisal Task Parameters

    Time frame: Baseline to 1 week, 1 month, and 3 months post-treatment

    Change in HGF-derived parameters of social inference and belief updating.

  3. Change in Beads Task Parameters

    Time frame: Baseline to 1 week, 1 month, and 3 months post-treatment

    Change in probabilistic reasoning bias related to delusion-proneness.

  4. Change in Prisoner's Dilemma Task Parameters

    Time frame: Baseline to 1 week, 1 month, and 3 months post-treatment

    Change in HGF-derived parameters of social inference.

  5. Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Score

    Time frame: Baseline to 1 week, 1 month, and 3 months post-treatment

    Change in clinician-rated depressive symptom severity. Total scores range from 0 to 60, with higher scores indicating greater severity.

  6. Change in Quick Inventory of Depressive Symptomatology (QIDS) Score

    Time frame: Baseline, Daily from Day 1 to Day 5, and at 1 week, 1 month, and 3 months post-treatment

    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.

Other outcomes

  1. Change in Heart Rate During Task Performance

    Time frame: Baseline to 1 week, 1 month, and 3 months post-treatment

    Heart rate recorded via BIOPAC physiological monitoring during the computational task battery, measured in beats per minute (bpm).

  2. Change in Galvanic Skin Response During Task Performance

    Time frame: Baseline to 1 week, 1 month, and 3 months post-treatment

    Galvanic skin response (electrodermal activity) recorded via BIOPAC physiological monitoring during the computational task battery, measured in microsiemens (µS).

  3. Change in Sleep Consolidation

    Time frame: Continuous, from 2-week baseline lead-in through 3-month follow-up

    Sleep consolidation (e.g., sleep efficiency, wake after sleep onset) recorded via Fitbit wearable device.

  4. Change in Daytime Activity Level

    Time frame: Continuous, from 2-week baseline lead-in through 3-month follow-up

    Daytime activity level (e.g., step count) recorded via Fitbit wearable device.

  5. Change in Geolocation-Based Mobility

    Time frame: Continuous, from 2-week baseline lead-in through 3-month follow-up

    Geolocation-based mobility patterns (e.g., time spent away from home, location variability) recorded via mindLAMP passive sensing.

  6. Change in Phone Usage Patterns

    Time frame: Continuous, from 2-week baseline lead-in through 3-month follow-up

    Smartphone usage patterns (e.g., screen time, app engagement) recorded via mindLAMP passive sensing.

  7. Change in Facial Expressivity

    Time frame: Continuous, from 2-week baseline lead-in through 3-month follow-up

    Facial expressivity recorded via the EMOCARE application using automated facial action unit analysis.

  8. Change in Vocal Prosody

    Time frame: Continuous, from 2-week baseline lead-in through 3-month follow-up

    Vocal prosody (e.g., pitch variability, speech rate) recorded via the EMOCARE application.

  9. Change in Speech Coherence

    Time frame: Baseline to 1 week, 1 month, and 3 months post-treatment

    Linguistic coherence features (e.g., semantic coherence) extracted from structured speech samples (Quebec Speech Bank), associated with thought disorder.

  10. Change in Speech Prosody

    Time frame: Baseline to 1 week, 1 month, and 3 months post-treatment

    Prosodic features (e.g., pitch, pause duration) extracted from structured speech samples (Quebec Speech Bank), associated with negative symptoms.

  11. Change in Structured Interview for Psychosis-Risk Syndromes (SIPS) Positive Symptom Score

    Time frame: Baseline to 1 week, 1 month, and 3 months post-treatment

    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.

  12. Change in Scale for the Assessment of Negative Symptoms (SANS) Total Score

    Time frame: Baseline to 1 week, 1 month, and 3 months post-treatment

    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.

  13. Change in Scale for the Assessment of Positive Symptoms (SAPS) Score

    Time frame: Baseline to 1 week, 1 month, and 3 months post-treatment

    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.

  14. Change in Positive and Negative Syndrome Scale (PANSS) Total Score

    Time frame: Baseline to 1 week, 1 month, and 3 months post-treatment

    Total scores range from 30 to 210, with higher scores indicating greater overall symptom severity.

  15. Change in Social and Occupational Functioning Assessment Scale (SOFAS) Score

    Time frame: Baseline to 1 week, 1 month, and 3 months post-treatment

    Scores range from 0 to 100, with higher scores indicating better functioning.

Study contacts

Contact information is provided by the study sponsor or research team.

Ashley Choucroun

CONTACT

[email protected]

5146593488

Sponsors and collaborators

Lead sponsor

Douglas Mental Health University Institute

Other

Registry information

Acronym: TMS-CHR

Important dates

Study start
2026
Primary completion
2028
Study completion
2029
First posted
Aug 26, 2026
Registry last updated
Aug 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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