Repetitive Transcranial Magnetic Stimulation of the Frontopolar Cortex for Cannabis Use Disorder: A Randomised Sham-Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 88
- 试验地点
- 1
- 主要终点
- Primary Outcomes
研究概览
简要总结
Summary of Research Synopsis
Title: Repetitive Transcranial Magnetic Stimulation of the Frontopolar Cortex for Cannabis Use Disorder: A Randomised Sham-Controlled Trial
- Background and Rationale
Cannabis Use Disorder (CUD) is a growing global concern, affecting up to 30% of cannabis users and contributing significantly to public health challenges. In India, cannabis is the most commonly used illicit substance, with a noticeable increase in treatment-seeking individuals. Current treatment strategies, primarily pharmacotherapy and behavioural interventions like CBT and MET, offer limited long-term effectiveness and are often associated with high relapse and dropout rates. Neurobiologically, addiction is linked to dysfunction in the prefrontal cortex (PFC), which governs impulse control, decision-making, and goal-setting. Within the PFC, the frontopolar cortex (FPC or Brodmann Area 10) is particularly involved in higher-order cognitive processes, including metacognition and future planning—functions that are often impaired in individuals with CUD. Repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive neuromodulation technique, has shown promise in reducing craving and improving executive function in other substance use disorders. While most rTMS research has targeted the dorsolateral prefrontal cortex (DLPFC), outcomes have been inconsistent. This study proposes targeting the FPC, hypothesizing that its unique cognitive role may offer more robust outcomes in treating CUD.
- Objectives and Hypotheses
Primary Objective: - Assess the efficacy of twice-daily high-frequency rTMS targeting the left FPC in reducing craving and cannabis use. Secondary Objectives: - Evaluate improvements in executive functioning, delay discounting, and emotional regulation. - Assess functional outcomes and quality of life. - Determine treatment durability and relapse prevention. - Compare tolerability and safety between active and sham stimulation. Hypotheses: - Active rTMS to the FPC will significantly reduce cannabis craving and use compared to sham. - It will improve executive and emotional functioning and be safe and well-tolerated.
- Methodology
Design: A randomized, double-blind, sham-controlled trial with two arms: - Active rTMS Group: High-frequency stimulation to the left FPC. - Sham Group: Mimicked stimulation without magnetic pulse delivery. Participants: 88 individuals aged 18–60, diagnosed with moderate to severe CUD, recruited from KIMS Bhubaneswar. Key exclusions include history of epilepsy, comorbid psychiatric disorders, metal implants, and pregnancy. Randomization & Blinding: Computer-generated block randomization with allocation concealed. All participants, TMS operators, and assessors will be blinded to treatment groups. Intervention Protocol: - 20 sessions over 2 weeks (twice daily on weekdays). - Active rTMS: 10 Hz, 110% RMT, targeting Fp1 site (FPC). - Sham rTMS: Identical setup using inactive coil or angled coil with sensory mimicry. Safety Monitoring: Pre/post-session symptom checklists, pregnancy tests, emergency protocols, and defined withdrawal criteria.
- Outcome Measures and Data Analysis
Primary Outcomes: - Cannabis craving measured weekly using the Marijuana Craving Questionnaire (MCQ-17). - Cannabis use evaluated via Timeline Follow-Back (TLFB) and urine THC tests. Secondary Outcomes: - Executive Function: Go/No-Go, Delay Discounting, BIS-11. - Emotion Regulation: DERS. - Functioning: WHODAS 2.0. - Relapse: Self-report and urine test-confirmed. Sample Size: Based on a moderate effect size, 88 participants (44 per group) are targeted. Data Collection & Analysis: Standardized tools at baseline, weeks 2, 4, 8, and 12. Analyses using repeated-measures ANOVA and ITT principles.
- Significance
This study is the first randomized controlled trial to explore the potential of frontopolar rTMS for treating CUD. By focusing on a cortical region critical for long-term planning and self-regulation, it aims to address fundamental cognitive deficits contributing to chronic cannabis use. If successful, it could pave the way for more effective, neuroscience-informed interventions for substance use disorders.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 60.00 Year(s)（—）
- 性别
- All
入选标准
- •Diagnosis of Cannabis Dependence Syndrome as per ICD-10 diagnostic criteria • Regular cannabis use on more than equal to20 of the past 30 days, confirmed by self-report and positive urine screening • Capacity to understand and provide written informed consent • Motivation to reduce or abstain from cannabis use during the study period • Patients with BPRS score less than equal to 31.
排除标准
- •History of seizure disorder, epilepsy, or significant neurological conditions Presence of metal implants, pacemakers, or any contraindications to rTMS Diagnosis of another substance use disorder (except nicotine or caffeine) within the past 6 months Acute suicidal ideation requiring emergency psychiatric care Pregnant or lactating women (confirmed by urine pregnancy test, if applicable) Presence of intellectual disability or significant cognitive impairment affecting consent or task performance Current participation in another clinical trial involving behavioural or neurostimulation interventions.
- •Severe psychiatric illnesses such as schizophrenia, mania, other mood, and psychotic disorders.
- •Any acute mood disorder or psychotic disorders arising due to substance use.
- •Patient is on mood stabilisers or antipsychotics.
结局指标
主要结局
Primary Outcomes
时间窗: Weekly for craving | Week 2,4,8 and 12 with urine screening
1. Cannabis Craving – Measured weekly using the Marijuana Craving Questionnaire 17 (MCQ-17)15.
时间窗: Weekly for craving | Week 2,4,8 and 12 with urine screening
2. Cannabis Use – Assessed via Timeline Follow-Back (TLFB)16 and confirmed with urine THC tests at baseline, Week 2, Week 4, Week 8, and Week 12.
时间窗: Weekly for craving | Week 2,4,8 and 12 with urine screening
次要结局
- 1. Impulse Control & Decision-Making – Evaluated using Go/No-Go Task17, Delay Discounting Task, & Barratt Impulsiveness Scale (BIS-11)18.(2. Emotion Regulation – Assessed with the DERS questionnaire19.)
研究者
Dr Anna Sehgal
Kalinga Institute of Medical Sciences, Bhubaneswar