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

Condition(s) studied

Investigational drug(s) / intervention(s)

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: 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.

Study summary

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.

Eligibility

Primary outcome measure(s)

• Treatment Initiation Rate — Through end of treatment week (Day 5)
  Proportion of consenting participants who begin the treatment protocol (receive at least one stimulation session).
• Treatment Acceptability Rate — Through study completion, an average of 18 months.
  Proportion of approached, eligible individuals who consent to participate in the study.
• Treatment Adherence — 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).
• Treatment Completion Rate — 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.
• Incidence of Adverse and Serious Adverse Events — 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.
• Qualitative Treatment Experience — 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.

Trial sites (1)

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