Accelerated Neuromodulation Therapy and Neurocomputational Biomarkers in Individuals at Clinical High Risk for Psychosis (TMS-CHR)

August 27, 2026 updated by: David Benrimoh, Douglas Mental Health University Institute

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Quebec
      • Verdun, Quebec, Canada, H4H1R3
        • Recruiting
        • McGill Lab for Computational Psychiatry and Translation
        • Contact:
        • Principal Investigator:
          • David Benrimoh

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Device: Active Intermittent Theta Burst Stimulation (BEAM-F3 Targeting)
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
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.
Device: Sham Comparator: Sham iTBS
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Through end of treatment week (Day 5)
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.
Through study completion, an average of 18 months.
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).
Through end of treatment week (Day 5)
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.
Through end of treatment week (Day 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.
Baseline through 3-month follow-up
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.
End of treatment (Day 5)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline to 1 week, 1 month, and 3 months post-treatment
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.
Baseline to 1 week, 1 month, and 3 months post-treatment
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.
Baseline to 1 week, 1 month, and 3 months post-treatment
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.
Baseline to 1 week, 1 month, and 3 months post-treatment
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.
Baseline to 1 week, 1 month, and 3 months post-treatment
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.
Baseline, Daily from Day 1 to Day 5, and at 1 week, 1 month, and 3 months post-treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Baseline to 1 week, 1 month, and 3 months post-treatment
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).
Baseline to 1 week, 1 month, and 3 months post-treatment
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.
Continuous, from 2-week baseline lead-in through 3-month follow-up
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.
Continuous, from 2-week baseline lead-in through 3-month follow-up
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.
Continuous, from 2-week baseline lead-in through 3-month follow-up
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.
Continuous, from 2-week baseline lead-in through 3-month follow-up
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.
Continuous, from 2-week baseline lead-in through 3-month follow-up
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.
Continuous, from 2-week baseline lead-in through 3-month follow-up
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.
Baseline to 1 week, 1 month, and 3 months post-treatment
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.
Baseline to 1 week, 1 month, and 3 months post-treatment
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.
Baseline to 1 week, 1 month, and 3 months post-treatment
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.
Baseline to 1 week, 1 month, and 3 months post-treatment
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.
Baseline to 1 week, 1 month, and 3 months post-treatment
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.
Baseline to 1 week, 1 month, and 3 months post-treatment
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.
Baseline to 1 week, 1 month, and 3 months post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Douglas Mental Health University Institute

Investigators

  • Principal Investigator: David Benrimoh, McGill University, Department of Psychiatry

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 1, 2026

Primary Completion (Estimated)

August 1, 2028

Study Completion (Estimated)

December 1, 2029

Study Registration Dates

First Submitted

August 19, 2026

First Submitted That Met QC Criteria

August 21, 2026

First Posted (Actual)

August 26, 2026

Study Record Updates

Last Update Posted (Actual)

August 28, 2026

Last Update Submitted That Met QC Criteria

August 27, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026-1387

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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