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.
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
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)
Parallel
Active Intermittent Theta Burst Stimulation (BEAM-F3 Targeting)
DeviceActive 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
DeviceSham 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.
Treatment Initiation Rate
Proportion of consenting participants who begin the treatment protocol (receive at least one stimulation session).
Treatment Acceptability Rate
Proportion of approached, eligible individuals who consent to participate in the study.
Treatment Adherence
Number of treatment sessions completed per participant, out of the planned schedule (up to 10 sessions/day over 5 days).
Treatment Completion Rate
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.
Change in Affective Conditioned Hallucinations Task Parameters
Change in individual-level information-processing parameters (Hierarchical Gaussian Filter modeling) derived from an affective variant of the Conditioned Hallucinations task.
Change in Social Appraisal Task Parameters
Change in HGF-derived parameters of social inference and belief updating.
Change in Beads Task Parameters
Change in probabilistic reasoning bias related to delusion-proneness.
Change in Prisoner's Dilemma Task Parameters
Change in HGF-derived parameters of social inference.
Change in Heart Rate During Task Performance
Heart rate recorded via BIOPAC physiological monitoring during the computational task battery, measured in beats per minute (bpm).
Change in Galvanic Skin Response During Task Performance
Galvanic skin response (electrodermal activity) recorded via BIOPAC physiological monitoring during the computational task battery, measured in microsiemens (µS).
Change in Sleep Consolidation
Sleep consolidation (e.g., sleep efficiency, wake after sleep onset) recorded via Fitbit wearable device.
Change in Daytime Activity Level
Daytime activity level (e.g., step count) recorded via Fitbit wearable device.
Click on the lead sponsor to view all of their trials.
