ChiCTR1800018067 版本V1.0 版本创建时间2020/11/22 21:26:14 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

ChiCTR1800018067 

最近更新日期：

Date of Last Refreshed on：

2018-08-29 10:54:05 

注册时间：

Date of Registration：

2018-08-29 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

经颅磁刺激联合电针治疗重性抑郁障碍的事件相关电位研究

Public title：

Event-related potential Study of Repetitive Transcranial Magnetic Stimulation plus Electroacupuncture for Treatment of Major Depression Disorder

注册题目简写：

English Acronym：

研究课题的正式科学名称：

重复经颅磁刺激联合电针治疗重性抑郁障碍的事件相关电位研究

Scientific title：

Event-related potential Study of Repetitive Transcranial Magnetic Stimulation plus Electroacupuncture for Treatment of Major Depression Disorder

研究课题代号(代码)：

Study subject ID：

在二级注册机构或其它机构的注册号：

The registration number of the Partner Registry or other register：

申请注册联系人：

郭小川 

研究负责人：

郑重 

Applicant：

Guo Xiaochuan 

Study leader：

Zheng Zhong 

申请注册联系人电话：

Applicant telephone：

+86 15915836842

研究负责人电话：

Study leader's telephone：

+86 18980601861

申请注册联系人传真 ：

Applicant Fax：

研究负责人传真：

Study leader's fax：

申请注册联系人电子邮件：

Applicant E-mail：

sonicxm@126.com

研究负责人电子邮件：

Study leader's E-mail：

zhengzhong1963@qq.com

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

研究负责人网址(自愿提供)：

Study leader's website(voluntary supply)：

申请注册联系人通讯地址：

四川省成都市武侯区电信南路28号

研究负责人通讯地址：

四川省成都市武侯区电信南路28号

Applicant address：

28 Dianxin Road South, Wuhou District, Chengdu, Sichuan, China

Study leader's address：

28 Dianxin Road South, Wuhou District, Chengdu, Sichuan, China

申请注册联系人邮政编码：

Applicant postcode：

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

四川大学华西医院

Applicant's institution：

West China Hospital, Sichuan University

研究负责人所在单位：

四川大学华西医院

Affiliation of the Leader：

West China Hospital, Sichuan University

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

2018-22

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

四川大学华西医院临床试验与生物医学伦理专委会

Name of the ethic committee：

Special committee on clinical trials and biomedical ethics, west China hospital, sichuan university

伦理委员会批准日期：

Date of approved by ethic committee：

1990-01-01 00:00:00

伦理委员会联系人：

左泽锦

Contact Name of the ethic committee：

Zuo Zejin

伦理委员会联系地址：

四川省成都市武侯区国学巷37号四川大学华西医院老八教四楼412室

Contact Address of the ethic committee：

Room 412, Old Eighth Teaching Building, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

伦理委员会联系人邮箱：

Contact email of the ethic committee：

研究实施负责（组长）单位：

四川大学华西医院

Primary sponsor：

West China Hospital, Sichuan University

研究实施负责（组长）单位地址：

四川省成都市武侯区电信南路28号

Primary sponsor's address：

28 Dianxin Road South, Wuhou District, Chengdu, Sichuan, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

四川省

市(区县)：

Country：

China

Province：

Sichuan

City：

单位(医院)：

四川大学华西医院

具体地址：

四川省成都市武侯区电信南路28号

Institution
hospital：

West China Hospital, Sichuan University

Address：

28 Dianxin Road South, Wuhou District, Chengdu, Sichuan, China

经费或物资来源：

自费

Source(s) of funding：

Self-supporting

Target disease：

Major depression disorder

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 治疗新技术临床试验 

Study phase：

New Treatment Measure Clinical Study

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

本研究拟通过前瞻和平行对照实验，采用事件相关电位的失匹配负波（miss match negative ，MMN）、P300和感觉门控电位P50（sensory gating P50，SG-P50）技术指标，研究rTMS联合电针对与大脑高级功能（自动加工、控制加工、感觉门控及认知功能等）相关的神经电生理的影响，以探讨电针和rTMS治疗重性抑郁障碍（major depressive disorder ，MMD）的机理。  

Objectives of Study：

This predictive and parallel controlled experiment study intends to use event-related potential(ERP) ,mismatch negative (MMN), P300, and sensory gating P50 (SG-P50) to explore the effects of electroacupuncture combine with rTMS on major depressive disorder (MMD) in response to neurophysiological effects associated with advanced brain functions (automated processing, controlled processing, sensory gating, and cognitive function).

药物成份或治疗方案详述：

70例患者被随机分为rTMS组和EA联合rTMS组，rTMS组采用rTMS治疗，另一组采用rTMS联合电针治疗，两组的基础治疗均使用SSRI类药物。 （1）rTMS治疗：采用中国依瑞德公司生产CCY-I型经颅磁刺激仪，以“8”字线圈中心置于受试者颞部皮层，通过磁刺激仪的肌电放大器在对侧手部鱼际肌记录MEPs，调整刺激部位和刺激量至10次刺激中至少有5次诱发的MEPs波幅大于50微伏（μV），此时的刺激输出量即为MT，在引出MEPs部位水平前移4~5 cm，该部位即为rTMS治疗部位，即背外额叶(dorsolateral prefrontal cortex ，DLPFC)。本研究采用90%MT进行双侧刺激，即1Hz低频（10脉冲/串，10sec串间隔）rTMS刺激右侧DLPFC；20Hz 高频（20脉冲/串，20sec串间隔）刺激左侧DLPFC，左、右侧刺激脉冲总数分别为800/D，每日刺激总脉冲数1600次。每天进行1次rTMS治疗，连续治疗5天休息2天，实际共治疗20天。 （2）电针治疗：采用调神舒肝法，穴位采用百会、印堂、合谷、神门、内关、风池、太冲。并根据患者的不同临床症状选用穴位对症治疗。本研究方案参考以上及符文彬教授多年实践经验结合腹部针刺中脘、下脘、气海、关元。隔日进行1次治疗，连续治疗3次后休息1天，实际治疗10次。 电针操作方法：针百会、针与头皮呈30。角，快速刺入头皮下，进针0.5寸；针印堂，平刺0.5寸。百会、印堂提均均匀捻转，得气即止，百会穴向前平刺，印堂穴向上平刺。得气后接电针仪，低频2Hz,波形为疏密波或连续波。其余各穴直刺0.5—1寸。内关、太冲行捻转泻法，其余各穴依照虚则补之、实则泻之的原则，留针20分钟。 （3）基本药物治疗：所有患者从观察之日开始均持续给予足量选择性5-羟色胺重摄抑制剂（selective serotonin reuptake inhibitor，SSRI）抗抑郁药物：帕罗西汀、舍曲林、西酞普兰、氟西汀、氟伏沙明治疗，治疗过程中无加减药量及更换药物，根据患者睡眠情况酌量给予苯二氮啅类（阿普唑仑、氯硝安定）药物。 

Description for medicine or protocol of treatment in detail：

Seventy patients were randomized into rTMS group and EA plus rTMS group. rTMS group was treated with rTMS, and the other group was treated with rTMS combined with electroacupuncture. SSRI drugs were used in the basic treatment of both groups. (1) rTMS treatment: CRY-I transcranial magnetic stimulator was produced by China Irrid Co., Ltd., and the center of the "8" coil was placed in the temporal cortex of the subject, and the myoelectric amplifier of the magnetic stimulator was on the opposite side thenar eminence. The MEPs were recorded in the opposite side thenar eminence,The amplitude of the MEPs was greater than 50 microvolts (μV) at least , and the level of MEPs was extracted.The MEPs is advanced 4 to 5 cm, which is the rTMS treatment site, ie the dorsolateral prefrontal cortex (DLPFC). In this study, 90% MT was used for bilateral stimulation, ie 1 Hz low frequency (10 pulses/string, 10 sec string interval) rTMS stimulation of right DLPFC; 20 Hz high frequency (20 pulses/string, 20 sec string interval) stimulated left DLPFC, left, The total number of stimulation pulses on the right side was 800/D, and the total number of pulses per day was 1600. The rTMS treatment was performed once a day, and the treatment was continued for 5 days for 2 days, and the actual treatment was for 20 days. 2) Electroacupuncture treatment: The method of adjusting the mind and relieving the liver is adopted, and the acupoints are Baihui, Yintang, Hegu, Shenmen, Neiguan, Fengchi and Taichong. According to the different clinical symptoms of patients, acupoint symptomatic treatment is selected. The research program refers to the above and Professor Fu Wenbin's many years of practical experience combined with abdominal acupuncture in thezhongwan xiawan, Qihai, Guanyuan. One treatment was performed every other day, and after three consecutive treatments, the rest was performed for one day, and the actual treatment was performed 10 times. Electroacupuncture operation method: the needle and the scalp is 30 angle at baihui yintang.Corner, quickly pierce the scalp, into the needle 0.5 inch; needle-printing hall, flat thorn 0.5 inch. Baihui and Yintangti were evenly twirling, and the gas was stopped. Baihui points were flattened forward and Yintang points were flat. After the gas is connected to the electro-acupuncture instrument, the low frequency is 2 Hz, and the waveform is a dense wave or a continuous wave. The remaining points are straight 0.5-1 inch. Neiguan, Tai Chong, sputum and diarrhea, the rest of the points according to the principle of supplementing the virtual, but actually diarrhea, leaving the needle for 20 minutes. (3) Essential drug treatment: All patients continued to receive a sufficient amount of selective serotonin reuptake inhibitor (SSRI) antidepressant drugs from the day of observation: paroxetine, sertraline, citalopram , fluoxetine, fluvoxamine treatment, no increase or decrease in the amount of drugs during the treatment and replacement of drugs, according to the patient's sleep, benzodiazepines (alprazolam, clonazepam) drugs. 

纳入标准：

患者受试者:
①年龄与利手：18-65岁，右利手（根据左、右手执笔书写比较）。全部参加治疗研究的参与者均来源于四川大学华西医院门诊就诊患者，符合DSM-IV关于抑郁发作的诊断标准，同意参加本研究。
②首发或停用抗抑郁药物治疗3月以上复发的MMD患者。汉密尔顿抑郁量表（HAMD）评分大于17分的轻度或中度抑郁，大于35分的重度抑郁。
正常对照组
①年龄与利手：18-60岁，右利手（根据左、右手执笔书写比较）。
②无精神疾病患病史。
③无精神疾病家族史（从自己数二系三代内无人患过精神疾病）。
④无重大精神创伤史。
⑤无神经系统疾病（如：脑血栓、脑梗死、脑血管瘤、周围神经疾病等）。
⑥无头部外伤史（指伤后出现昏迷、呕吐、失忆、抽搐或送医急救的情况）。
⑦无眼外伤史、眼球和眼外肌疾病史。
⑧无糖尿病、高血压、肝硬化、胃肠溃疡、恶性肿瘤患病史。
⑨无艾滋、梅毒、淋病患病史。
⑩无吸毒、酗酒等不良嗜好。

Inclusion criteria

Patient subject:
1. all participants in the treatment study were from outpatient patients in West China Hospital of Sichuan University, meeting the diagnostic criteria of dsm-iv for depressive episode, and agreed to participate in this study.
2. Aged 18-65 years old, right handedness (according to left and right hand).
MMD patients who had relapsed at least 3 months after the first or discontinued antidepressant therapy.The Hamilton depression scale (HAMD) scores were greater than 17 for mild or moderate depression and greater than 35 for severe depression.
Normal control group
1. Age and handedness: 18-60 years old, right handedness (according to left and right hand).
2. No history of mental illness.
3. No family history of mental illness (no one has suffered from mental illness in the second and third generations of the family).
4. No history of major trauma.
5. No neurological diseases (e.g., cerebral thrombosis, cerebral infarction, cerebral hemangioma, peripheral neuropathy, etc.)
6. The patient presented with no history of head trauma (including coma, vomiting, memory loss, convulsion, or first aid).
7. No history of ocular trauma, ocular and extraocular muscle diseases.
8. No history of diabetes, hypertension, liver cirrhosis, gastrointestinal ulcer, malignant tumor.
9. No history of AIDS, syphilis and gonorrhea.
10. No drug or alcohol addiction.

排除标准：

排除标准：①躯体疾病：甲亢、甲低或糖尿病等内分泌系统疾病；②脑器质性疾病：产伤、外伤、脑炎、肿瘤等；③周围神经以及肌肉系统病变；④患其他精神疾病：精神分裂症，焦虑症，强迫症等；⑤既往有过躁狂或轻躁狂史；⑤近期服用过可能致情绪障碍等的药物：如利血平等；⑦酒精滥用或精神活性物质滥用史；⑧妊娠期或哺乳期女性；⑨视力及听力障碍患者；⑩任何不能进入高磁场环境的情况（安置心脏起搏器、安置深部脑刺激器、安置迷走神经刺激器、安置金属内固定器材等）。

Exclusion criteria：

1. dependent somatic diseases: hyperthyroidism, hypothyroidism or diabetes and other endocrine system diseases;
2. cerebral organic diseases: birth injury, trauma, encephalitis, tumor, etc.;
3. Peripheral nerve and muscle system lesions;
4. Suffering from other mental diseases: schizophrenia, anxiety, obsessive-compulsive disorder, etc.;
5. There has been a history of mania or hypomania in the past of mania;
6. Recently took medications that can cause mood disorders, such as blood and blood equality;
7. A history of alcohol abuse or psychoactive substance abuse;
8. The woman who was during pregnancy or lactation;
9. Patients with visual and hearing impairment;
10. Any situation that cannot enter the high magnetic field environment (placement of cardiac pacemaker, placement of deep brain stimulator, placement of vagus nerve stimulator, placement of metal internal fixation equipment, etc.)

研究实施时间：

Study execute time：

从 From 2018-03-17 00:00:00至 To 2018-09-17 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2018-03-17 00:00:00 至 To 2018-08-01 00:00:00  

干预措施：

Interventions：

组别：

rTMS组

样本量：

35

Group：

rTMS组

Sample size：

干预措施：

rTMS

干预措施代码：

Intervention：

rTMS

Intervention code：

组别：

EA+rTMS组

样本量：

35

Group：

EA+rTMS group

Sample size：

干预措施：

EA+rTMS

干预措施代码：

Intervention：

EA+rTMS

Intervention code：

组别：

健康对照组

样本量：

35

Group：

Healthy controls

Sample size：

干预措施：

none

干预措施代码：

Intervention：

none

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

测量指标：

Outcomes：

指标中文名：

汉密尔顿抑郁量表24项

指标类型：

主要指标

Outcome：

HAMD-24

Type：

Primary indicator

测量时间点：

治疗前，治疗10天，治疗20天，随访30天

测量方法：

Measure time point of outcome：

Before treatment, 10 days were treated, 20 days were treated and 30 days were followed up

Measure method：

指标中文名：

汉密尔顿焦虑量表14项

指标类型：

次要指标

Outcome：

HAMA-14

Type：

Secondary indicator

测量时间点：

治疗前，治疗10天，治疗20天，随访30天

测量方法：

Measure time point of outcome：

Before treatment, 10 days were treated, 20 days were treated and 30 days were followed up

Measure method：

指标中文名：

线段等分实验量表（LBT）

指标类型：

次要指标

Outcome：

Line segment scale (LBT)

Type：

Secondary indicator

测量时间点：

治疗前，治疗10天，治疗20天，随访30天

测量方法：

Measure time point of outcome：

Before treatment, 10 days were treated, 20 days were treated and 30 days were followed up

Measure method：

指标中文名：

中医症候量表

指标类型：

次要指标

Outcome：

TCM syndrome scale

Type：

Secondary indicator

测量时间点：

治疗前，治疗10天，治疗20天，随访30天

测量方法：

Measure time point of outcome：

Before treatment, 10 days were treated, 20 days were treated and 30 days were followed up

Measure method：

指标中文名：

失匹配负波

指标类型：

次要指标

Outcome：

Mismatched negative wave (MMN)

Type：

Secondary indicator

测量时间点：

治疗前，治疗10天，治疗20天，随访30天

测量方法：

Measure time point of outcome：

Before treatment, 10 days were treated, 20 days were treated and 30 days were followed up

Measure method：

指标中文名：

P300

指标类型：

次要指标

Outcome：

P300

Type：

Secondary indicator

测量时间点：

治疗前，治疗10天，治疗20天，随访30天

测量方法：

Measure time point of outcome：

Before treatment, 10 days were treated, 20 days were treated and 30 days were followed up

Measure method：

指标中文名：

P50

指标类型：

次要指标

Outcome：

P50

Type：

Secondary indicator

测量时间点：

治疗前，治疗10天，治疗20天，随访30天

测量方法：

Measure time point of outcome：

Before treatment, 10 days were treated, 20 days were treated and 30 days were followed up

Measure method：

指标中文名：

副反应量表

指标类型：

次要指标

Outcome：

treatment emergent symptom scale ，TESS

Type：

Secondary indicator

测量时间点：

治疗10天，治疗20天

测量方法：

Measure time point of outcome：

treated10days, 20 days

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

征募研究对象情况：

Recruiting status：

正在进行

Recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 70 岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

治疗组采用SAS统计分析系统，给定种子数，产生70例患者接受干预的随机分配，即列出流水号为001-70所对应的治疗分配至rTMS组和EA+rTMS组

Randomization Procedure (please state who generates the random number sequence and by what method)：

In the treatment group, the SAS statistical analysis system was used, and the seed number was given, resulting in the random allocation of 70 patients receiving the intervention, that is, the treatment corresponding to the serial number 001-70 was assigned to the rTMS group and the EA+rTMS group

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：

对评价者及数据统计者设盲

Blinding：

是否共享原始数据：

IPD sharing

Yes

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

临床试验公共管理平台 http://www.medresman.org/login.aspx

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

Clinical Trial Management Public Platform http://www.medresman.org/login.aspx

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

1.CRF 2.EDC(resman)

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

1.CRF 2.EDC（resman）

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2018-08-29 10:54:05