Effects of Theta-burst Transcranial Magnetic Stimulation on Serotonin-1A Receptor Binding in Treatment Resistant Depression
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Regional 5-HT1A receptor binding
研究概览
简要总结
Background:
Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS) holds promise as an effective treatment for treatment resistant depression (TRD). rTMS has been linked to neuroplastic changes as shown using magnetic resonance imaging (MRI) and positron emission tomography (PET). Alterations in serotonin-1A receptor expression (5-HT1A) have been linked to major depression. Moreover, changes in 5-HT1A receptor binding - observed after pharmacological treatment, as well as after electroconvulsive therapy - has been linked to neuronal adaptations in response to these antidepressant treatments.
Objectives of the study:
Here, the aim is to investigate the effects of TBS over left and right dorsolateral prefrontal cortex on the 5-HT1A receptor binding in patients with TRD using PET. In addition, effects of iTBS on brain structure and function will be determined using functional, structural and perfusion MRI.
Study population:
80 patients with TRD who maintain their original medication regimen will be recruited.
Study design:
Longitudinal, randomized and double-blind clinical trial. 40 patients will receive active TBS, 40 patients will receive sham TBS for treatment duration of three weeks. Before and after three weeks of treatment, patients will be scanned using MRI and PET with the highly specific and selective radiotracer [carbonyl-11C]WAY100635. A follow-up visit and final examination will be performed 2 and 4 weeks after treatment for the active TBS group, respectively. Patients in the sham TBS arm will receive active TBS treatment immediately after the second MRI and PET scan.
Relevance and implications of the study:
This will be the worldwide first multimodal imaging study to investigate the effects of TBS on serotonin-1A receptor binding in TRD using PET. Thus, the study will add crucial knowledge to the existing literature on the effects of TMS on brain structure and function, related to antidepressant efficacy. Moreover, by combining molecular imaging of serotonergic neurotransmission with structural and functional MRI, the proposed study will increase the investigators knowledge on the serotonergic role in shaping brain morphology, microstructure and structural/functional connectivity. Taken together, the study has the potential to contribute to the development of personalized treatment, the reduction of personal suffering and the reduction of costs and occupational disability.
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, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DSM-5 diagnosis of single or recurrent major depression
- •HAMD-17 total score of ≥ 18 and a Clinical Global Impression Scale (CGI-S) of ≥ 4
- •Failure of at least two adequate antidepressant treatments
- •Age 18-65 years
- •Right-handedness (assessed with the Edinburgh Handedness Inventory)
排除标准
- •Seizures in medical history
- •Lifetime medical history of major systemic illness, neurological disorders and previous brain injuries
- •Ferromagnetic implants, cardiac pacemaker, deep brain stimulation and other common MRI exclusion criteria
- •Lifetime history of psychotic disorders or current psychotic symptoms
- •Substance abuse or dependence within the last 3 months
- •Borderline personality disorder (based on DSM-5 criteria)
- •Pregnancy
- •Active suicidal intent
- •Benzodiazepines other than Lorazepam > 2mg/d or any dose of an anticonvulsant
- •for participants who participated in an earlier neuroimaging study using ionizing radiation, the total radiation exposure dose of 20 mSv over the last 10 years must not be exceeded, as specified in the legislation on radiation protection.
- •failure to comply with the study protocol or to follow the instructions of the investigating team
研究组 & 干预措施
active TBS
40 patients with TRD will receive active theta-burst stimulation using a MagPro X1000 between the two PET measurements
干预措施: theta-burst stimulation using a MagPro X1000 (Device)
sham TBS
40 patients with TRD will receive sham stimulation using a MagPro X1000 between the two PET measurements. After the second PET scan they will receive active TBS
干预措施: sham stimulation using a MagPro X1000 (Device)
结局指标
主要结局
Regional 5-HT1A receptor binding
时间窗: before and after 3 weeks of TBS treatment
5-HT1A receptor binding using the radioligand \[carbonyl-11C\]WAY100635
次要结局
- Functional connectivity at rest and during tasks(before and after 3 weeks of TBS treatment)
- Regional white matter microstructure using DWI-TBSS(before and after 3 weeks of TBS treatment)
- Regional grey matter volume using MRI(before and after 3 weeks of TBS treatment)
- Regional brain perfusion(before and after 3 weeks of TBS treatment)
- Regional white matter microstructure using DWI-Tractography(before and after 3 weeks of TBS treatment)
研究者
Rupert Lanzenberger
Assoc.-Prof. PD MD
Medical University of Vienna