Accelerated Neuromodulation Therapy and Neurocomputational Biomarkers in Individuals at Clinical High Risk for Psychosis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Treatment Initiation Rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
Participants, treaters (care providers), and raters (outcomes assessors) are blinded to treatment allocation. Blinding is supported by device-integrated sham stimulation (MagVenture Cool B65 A/P coil) and topical application of 2% lidocaine jelly to the stimulation site in both arms. Blinding integrity is formally assessed at multiple time points across the study.
入排标准
- 年龄范围
- 18 Years 至 34 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Sham Comparator: Sham iTBS (Device)
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.
干预措施: Active Intermittent Theta Burst Stimulation (BEAM-F3 Targeting) (Device)
结局指标
主要结局
Treatment Initiation Rate
时间窗: 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
时间窗: Through study completion, an average of 18 months.
Proportion of approached, eligible individuals who consent to participate in the study.
Treatment Adherence
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Change in Affective Conditioned Hallucinations Task Parameters(Baseline to 1 week, 1 month, and 3 months post-treatment)
- Change in Social Appraisal Task Parameters(Baseline to 1 week, 1 month, and 3 months post-treatment)
- Change in Beads Task Parameters(Baseline to 1 week, 1 month, and 3 months post-treatment)
- Change in Prisoner's Dilemma Task Parameters(Baseline to 1 week, 1 month, and 3 months post-treatment)
- Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Score(Baseline to 1 week, 1 month, and 3 months post-treatment)
- Change in Quick Inventory of Depressive Symptomatology (QIDS) Score(Baseline, Daily from Day 1 to Day 5, and at 1 week, 1 month, and 3 months post-treatment)
研究者
David Benrimoh
Neuropsychiatrist
Douglas Mental Health University Institute