Effectiveness of rTMS as Maintenance Therapy; Clustered rTMS vs. Tapered rTMS
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Time to depressive relapse or clinically relevant symptom worsening
研究概览
简要总结
The goal of this clinical trial is to compare two maintenance transcranial magnetic stimulation (rTMS) strategies following successful acute theta burst stimulation (TBS) treatment in adults with depressive syndrome. It will also evaluate whether the two maintenance strategies differ in their ability to maintain the antidepressant treatment response over 24 weeks. The main questions it aims to answer are:
Does clustered maintenance rTMS reduce the risk of depressive relapse or clinically relevant symptom worsening compared with tapered maintenance rTMS? Do the two maintenance strategies differ in depressive symptoms, global clinical status, psychosocial functioning, and MRI-based biomarkers over time?
Researchers will compare a clustered maintenance rTMS protocol with a tapered maintenance rTMS protocol.
Participants will:
- Complete successful acute TBS treatment before study enrollment
- Be randomly assigned to either clustered or tapered maintenance rTMS
- Receive 20 maintenance stimulation sessions over 20 weeks
- Attend clinical follow-up assessments every 4 weeks for a total follow-up -period of 24 weeks
- Undergo optional multimodal MRI examinations at the Munich study site
详细描述
Repetitive transcranial magnetic stimulation (rTMS), including intermittent theta burst stimulation (iTBS), is an established treatment for depressive disorders. While the efficacy of acute treatment has been demonstrated in numerous clinical trials, a substantial proportion of patients experience symptom worsening or relapse following successful acute treatment if no maintenance therapy is provided. Several maintenance strategies have been proposed, including tapered treatment schedules with gradually decreasing treatment frequency and clustered treatment schedules consisting of repeated blocks of consecutive stimulation sessions. However, the available evidence is limited, and no randomized controlled trial has directly compared these two maintenance approaches using identical treatment duration and the same total number of stimulation sessions.
This prospective, randomized, controlled, two-center study aims to compare two maintenance treatment strategies following successful acute iTBS in adults with depressive syndrome. Patients who achieve response or remission after a standardized acute iTBS treatment course will be randomized in a 1:1 ratio to either a tapered maintenance protocol or a clustered maintenance protocol. Randomization will be stratified by study site and baseline depression severity. Because of the different treatment protocols, blinding of participants and treating clinicians is not feasible. MRI data analyses will be performed blinded to treatment allocation.
Both maintenance protocols include 20 stimulation sessions delivered over a 20-week maintenance period following a four-week stimulation-free interval after completion of the acute treatment phase. The treatment protocols differ only in the temporal distribution of maintenance sessions. The tapered protocol gradually reduces treatment frequency over time, whereas the clustered protocol delivers stimulation in four clusters of five consecutive daily sessions.
The primary objective is to compare the time to depressive relapse or clinically relevant symptom worsening during the 24-week follow-up period. Clinically relevant symptom worsening is defined using predefined changes in the Montgomery-Åsberg Depression Rating Scale (MADRS), and relapse is defined as the recurrence of at least moderate depressive symptoms together with loss of the previously achieved treatment response.
Secondary objectives include comparing longitudinal changes in depressive symptom severity, patient-reported depressive symptoms, global clinical status, and psychosocial functioning using the MADRS, Beck Depression Inventory (BDI), Clinical Global Impression (CGI), and Global Assessment of Functioning (GAF), respectively.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
MRI data analyses will be performed blinded to treatment allocation. Participants and treating clinicians are not blinded because of the different treatment protocols.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Diagnosis of a depressive syndrome
- •Completion of an acute treatment course consisting of 20 sessions of theta burst stimulation (TBS) over 4 weeks
- •Response or remission following acute treatment. Response is defined as a ≥50% reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score
- •Remission is defined as a MADRS total score ≤
- •Clinical eligibility for maintenance TBS
- •Provision of written informed consent
排除标准
- •Non-response to acute TBS treatment
- •Contraindications to transcranial magnetic stimulation (TMS) or theta burst stimulation (TBS)
- •Active substance use disorder (substance use within the past 3 months)
- •Acute psychiatric or medical conditions that preclude study participation
- •Additional exclusion criteria for the MRI component:
- •- Contraindications to MRI (e.g., non-MRI-compatible metallic implants or severe claustrophobia)
结局指标
主要结局
Time to depressive relapse or clinically relevant symptom worsening
时间窗: From randomization through Week 24
Time from randomization to the first occurrence of depressive relapse or clinically relevant symptom worsening during the 24-week follow-up period. Clinically relevant symptom worsening is defined as a transition to a higher depression severity category together with an increase of at least 5 points in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Relapse is defined as recurrence of at least moderate depressive symptoms (MADRS ≥20) together with loss of the previously achieved treatment response.
次要结局
- Change in Montgomery-Åsberg Depression Rating Scale Total Score(Baseline and Weeks 4, 8, 12, 16, 20, and 24)
- Change in Beck Depression Inventory II Total Score(Baseline and Weeks 4, 8, 12, 16, 20, and 24)
- Change in Global Assessment of Functioning Score (GAF)(Baseline and Weeks 4, 8, 12, 16, 20, and 24)
- Change in Clinical Global Impression Score (CGI)(Baseline and Weeks 4, 8, 12, 16, 20, and 24)
- Change in Resting-State Functional Connectivity(During Maintenance rtMS Week 0-24)
- Change in Cerebral Perfusion Measured by Arterial Spin Labeling(During maintenance treatment week 0-24)
- Change in Diffusion MRI Measures of Structural Connectivity and Microstructure(during maintenance treatment week 0 to 24)
- Change in Quantitative MRI Parameters(During maintenance treatment week 0-24)
研究者
Ulrike Vogelmann
Privatdozentin, Senior Physician, Department of Psychiatry and Psychotherapy
Technical University of Munich