D-Cycloserine Augmentation of Intermittent Theta Burst Stimulation (iTBS) in Depression: A Multi-Site, Randomised, Placebo-Controlled Trial (COGENT)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Rate of treatment response as per Montgomery Åsberg Depression Rating Scale (MADRS)
研究概览
简要总结
The goal of this clinical trial is to investigate if the drug D-Cycloserine (DCS) improves the antidepressant effects of Intermittent Theta Burst Stimulation (iTBS), a non-invasive brain stimulation therapy, in patients with Major Depressive Disorder (MDD). The main questions it aims to answer are:
- Whether taking DCS prior to iTBS therapy will be more effective in improving depressive symptoms than iTBS therapy alone.
- Compare the effect of DCS 100mg/day versus 50mg/day on depressive symptoms.
- Test the safety and tolerability of DCS. Participants will take either 50mg DCS per day, 100mg DCS or placebo prior to each iTBS treatment session. iTBS treatment will be administered daily, 5 days a week for 4 weeks. Clinical measures will be conducted at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.
详细描述
Major Depressive Disorder (MDD) is a common and debilitating condition with high rates of treatment resistance. Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for treatment-resistant depression with few adverse effects. Intermittent Theta Burst Stimulation (iTBS) is a time-efficient form of rTMS with evidence base in the treatment of treatment-resistant depression (TRD). The most commonly supported understanding of iTBS's mechanism of action appear to be its strengthening of connections between networks of neurons, which is modulated by the N-methyl-D-aspartate (NMDA) receptor. D-cycloserine (DCS) is a partial NMDA receptor agonist that has demonstrable impact on rTMS and TBS's neuromodulatory effects. This study protocol proposes the conduct of a prospective multi-site, parallel-arm design, randomized, double-blinded, placebo-controlled clinical trial to investigate DCS augmentation of iTBS in MDD. We will investigate if adjuvant DCS 50mg or 100mg/day might have superior iTBS antidepressant augmentation effects.
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
- Double (Participant, Investigator)
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
- •Diagnosis of major depressive episode (MDE), in accordance with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5), in the context of unipolar major depressive disorder or bipolar affective disorder.
- •18 years or older in age.
- •Treatment resistant depression at Stage II of the Thase and Rush classification.56
- •Baseline Montgomery Åsberg Depression Rating Scale score of ≥ 20 (moderate-to-severe depression severity).57,58
- •No increase or initiation of new antidepressant therapy in the four weeks prior to screening.
- •Demonstrated capacity to give informed consent.
排除标准
- •Inability to provide informed consent.
- •Medically unstable patients at the discretion of the investigator.
- •Concomitant neurological disorder or a history of a seizure disorder.
- •Participants who are pregnant.
- •Current substance use meeting DSM-5 criteria for substance use disorder.
- •Per DSM-5, had ever met diagnostic criteria for schizophrenia, schizoaffective disorder, schizophreniform disorder or delusional disorder as assessed by the Mini-International Neuropsychiatric Interview (MINI) at the time of screening.
- •Diagnosis of any other mental disorder that is the participant's primary diagnosis or main mental health syndrome of concern at the time of screening, which may significantly affect psychiatric status and assessed as likely to impact trial participation, in the clinical judgement of the investigator.
研究组 & 干预措施
Active iTBS + active DCS 50mg/day
Active iTBS (600 pulses), 5 days/week x 4 weeks + active DCS 50mg/day x 2 weeks, taken 2-hours prior to scheduled iTBS treatment.
干预措施: D-Cycloserine (Drug)
Active iTBS + active DCS 50mg/day
Active iTBS (600 pulses), 5 days/week x 4 weeks + active DCS 50mg/day x 2 weeks, taken 2-hours prior to scheduled iTBS treatment.
干预措施: Intermittent Theta Burst Stimulation (Device)
Active iTBS + active DCS 100mg/day
Active iTBS (600 pulses), 5 days/week x 4 weeks + active DCS 100mg/day x 2 weeks, taken 2-hours prior to scheduled iTBS treatment.
干预措施: D-Cycloserine (Drug)
Active iTBS + active DCS 100mg/day
Active iTBS (600 pulses), 5 days/week x 4 weeks + active DCS 100mg/day x 2 weeks, taken 2-hours prior to scheduled iTBS treatment.
干预措施: Intermittent Theta Burst Stimulation (Device)
Active iTBS + placebo
Active iTBS (600 pulses), 5 days/week x 4 weeks + placebo x 2 weeks, taken 2-hours prior to scheduled iTBS treatment.
干预措施: Intermittent Theta Burst Stimulation (Device)
结局指标
主要结局
Rate of treatment response as per Montgomery Åsberg Depression Rating Scale (MADRS)
时间窗: Determined at Week 4 (primary study endpoint)
Clinical treatment response defined as \>/= 50% reduction in MADRS scores from baseline to primary study endpoint. Clinician-administered depression rating scale. The overall score ranges from 0 - 60. Cutoff points are 0-6 = normal, 7-9 = mild depression, 20-34 = moderate depression, \>34 = severe depression.
次要结局
- International Trauma Questionnaire (ITQ)(Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.)
- Beck's Scale for Suicide Ideation (BSS)(Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.)
- Change in World Health Organization Quality of Life (WHOQOL-BREF)(Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.)
- Change in Montgomery Åsberg Depression Rating Scale (MADRS)(Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.)
- Change in Clinical Global Impression (CGI)(Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.)
- Change in Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR)(Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.)
- Beck's Anxiety Inventory (BAI)(Administered at baseline and at the ends of weeks 1, 2, 3 and 4 of treatment.)
研究者
Leo Chen
Head, Clinical TMS and Psychopharmacology Research Units, Monash Alfred Psychiatry Research Centre (MAPrc)
The Alfred