ChiCTR2500112550 版本V1.0 版本创建时间2025/11/17 09:16:55 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：

 ChiCTR2500112550 

最近更新日期：

Date of Last Refreshed on：

 2025-11-17 09:16:49 

注册时间：

Date of Registration：

 2025-11-17 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

伏隔核及内囊前肢脑深部电刺激治疗难治性精神分裂症有效性和安全性的前瞻性、单中心、双盲、随机对照研究

Public title：

Efficacy and safety of deep brain stimulation of the nucleus ambiguus and the anterior limb of the internal capsule in the treatment of refractory schizophrenia: A prospective, single-centre, double-blind, randomised controlled study

注册题目简写：

English Acronym：

研究课题的正式科学名称：

伏隔核及内囊前肢脑深部电刺激治疗难治性精神分裂症有效性和安全性的前瞻性、单中心、双盲、随机对照研究

Scientific title：

Efficacy and safety of deep brain stimulation of the nucleus ambiguus and the anterior limb of the internal capsule in the treatment of refractory schizophrenia: A prospective, single-centre, double-blind, randomised controlled study

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：

姚培森 

研究负责人：

康德智; 林元相 

Applicant：

Yao Peisen 

Study leader：

Kang Dezhi; Lin Yuanxiang 

申请注册联系人电话：

Applicant telephone：

 +86 186 5008 4102

研究负责人电话：

Study leader's
telephone：

+86 157 5941 3951

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：

 peisen.yao@163.com

研究负责人电子邮件：

Study leader's E-mail：

 kdz99988@vip.sina.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：

中国福建省福州市台江区茶中路20号

研究负责人通讯地址：

福建省福州市台江区茶中路20号

Applicant address：

No. 20 Chazhong Road, Taijiang District, Fuzhou, Fujian, China

Study leader's address：

No. 20 Chazhong Road, Taijiang District, Fuzhou, Fujian, 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：

福建医科大学附属第一医院

Applicant's institution：

The First Affiliated Hospital of Fujian Medical University

研究负责人所在单位：

福建医科大学附属第一医院

Affiliation of the Leader：

The First Affiliated Hospital of Fujian Medical University

是否获伦理委员会批准：

是

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

 闽医大附一伦理医研[2025]637号

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：

福建医科大学附属第一医院医学伦理委员会医学研究与临床技术应用分会

Name of the ethic committee：

Branch for Medical Research and Clinical Technology Application, Ethics Committee of the First Affiliated Hospital of Fujian Medical University

伦理委员会批准日期：

Date of approved by ethic committee：

 2025-09-10 00:00:00

伦理委员会联系人：

吴安鹏

Contact Name of the ethic committee：

Wu Anpeng

伦理委员会联系地址：

中国福建省福州市台江区茶中路 20 号

Contact Address of the ethic committee：

No. 20 Chazhong Road, Taijiang District, Fuzhou, Fujian, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 591 8798 1022

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：

福建医科大学附属第一医院

Primary sponsor：

The First Affiliated Hospital of Fujian Medical University

研究实施负责（组长）单位地址：

中国福建省福州市台江区茶中路 20 号

Primary sponsor's address：

No. 20 Chazhong Road, Taijiang District, Fuzhou, Fujian, 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)：

福建

市(区县)：

Country：

China

Province：

Fujian

City：

单位(医院)：

福建医科大学附属第一医院

具体地址：

中国福建省福州市台江区茶中路 20 号

Institution
hospital：

The First Affiliated Hospital of Fujian Medical University

Address：

No. 20 Chazhong Road, Taijiang District, Fuzhou, Fujian, China

经费或物资来源：

景昱医疗科技（苏州）股份有限公司

Source(s) of funding：

Jingyu Medical Technology (Suzhou) Co., Ltd.

研究疾病：

精神分裂症  

Target disease：

Schizophrenia

研究疾病代码：

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 其它 

Study phase：

N/A

研究设计：

随机交叉对照 

Study design：

Cross-over 

研究目的：

探讨伏隔核和内囊前肢脑深部电刺激治疗难治性精神分裂症有效性和安全性。  

Objectives of Study：

To investigate the efficacy and safety of deep brain stimulation of the nucleus accumbens and anterior limb of the internal capsule in the treatment of refractory schizophrenia.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1.在签署知情同意书时年龄 18-55周岁（含），男性或（非怀孕的）女性 2.符合DSM-5精神分裂症诊断标准； 3.在筛选访视之前，精神分裂症病程≥5年； 4.符合难治性和/或超难治性精神分裂症的标准（参照 2016 -TRRIP-难治性精神分裂症诊断标准），满足以下条件： a.既往接受过≥2种不同抗精神病药物（不包括氯氮平）足量（氯丙嗪≥600mg/日等效剂量）、足疗程（治疗≥12周）治疗无效，或不能耐受； b.经氯氮平足量（剂量≥300mg/日或者血药浓度≥350ng/ml）、足疗程（治疗≥12周）治疗无效，或不能耐受； c.症状严重度至少为中度； 5.筛选期和基线期 PANSS 总分≥70分 6.在过去2个月用药治疗没有变化。 7.患者及监护人在对研究目的、内容、预期治疗及风险等的充分说明并了解后，同意接受植入式神经刺激系统治疗并签署知情同意书。

Inclusion criteria

1.Aged 18-55 years (inclusive) at the time of signing the informed consent form, male or non-pregnant female; 2.Meets the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for schizophrenia; 3.Schizophrenia disease course >= 5 years before the screening visit; 4.Meets criteria for refractory and/or ultra-refractory schizophrenia (refer to the 2016 TRRIP criteria for refractory schizophrenia), satisfying the following: a. Previous treatment with >= 2 different antipsychotics (excluding clozapine) at adequate dose (>= 600mg/day chlorpromazine equivalent) and duration (>= 12 weeks) with no response or intolerance; b. Previous treatment with clozapine at adequate dose (>= 300mg/day or plasma concentration >= 350ng/ml) and duration (>= 12 weeks) with no response or intolerance; c. Symptom severity of at least moderate; 5.PANSS total score >= 70 at screening and baseline; 6.No changes in medication treatment in the past 2 months; 7.The patient and their guardian have been fully informed of the study purpose, content, expected treatment, and risks, agree to receive implantable neurostimulation system treatment, and sign the informed consent form.

排除标准：

1.伴有癫痫、严重认知障碍（MMSE评分小于10分）、器质性精神障碍、偏执型人格障碍、精神发育迟滞、以及除尼古丁以外的成瘾等精神疾病； 2.植入过人工耳蜗、心脏起搏器、心脏除颤器、曾经植入过单侧或双侧同类产品或半年内做过研究者认为对本试验有影响的外科手术者； 3.存在DBS植入手术禁忌症，经研究者评估认为不适合手术者； 4.目前正在参与或在筛选前3个月内曾参与过其他药物或医疗器械临床试验者； 5.确诊的 HIV阳性者； 6.妊娠期、哺乳期妇女，或育龄期妇女筛选期血HCG/尿妊娠检查结果阳性者；或试验期间无法采取有效避孕措施者；或计划在试验开始后的3个月内受（授）孕者； 7.研究者认为其他不适宜参加本项临床研究者；

Exclusion criteria：

1.Comorbid with epilepsy, severe cognitive impairment (MMSE score < 10), organic mental disorder, paranoid personality disorder, mental retardation, or addiction (other than nicotine); 2.Has implanted cochlear implants, cardiac pacemakers, implantable cardioverter-defibrillators, unilateral/bilateral similar devices, or undergone surgery within 6 months that the investigator deems may affect the trial; 3.Has contraindications to DBS implantation, deemed unsuitable for surgery by the investigator; 4.Currently participating in or has participated in other drug or medical device clinical trials within 3 months before screening; 5.Confirmed HIV-positive; 6.Pregnant or lactating women; women of childbearing age with positive blood HCG/urine pregnancy test at screening; those unable to use effective contraception during the trial; or those planning to conceive within 3 months after trial initiation; 7.Other conditions deemed unsuitable for participation by the investigator.

研究实施时间：

Study execute time：

从 From 2025-12-01 00:00:00至 To 2028-12-01 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2025-12-01 00:00:00 至 To 2027-11-01 00:00:00

干预措施：

Interventions：

组别：

试验组1

样本量：

 5

Group：

Group 1

Sample size：

干预措施：

行伏隔核和内囊前肢脑深部电刺激（DBS），DBS植入术后2周后开机进行单纯伏隔核刺激，开机（6周）至术后第8周后关机，然后第10周开机进行单纯内囊前肢刺激，开机（6周）后至第16周关机。随后在术后第18周进行开机，进行伏隔核和内囊前肢联合刺激，联合刺激6周后进行效果评价。

干预措施代码：

Intervention：

Deep Brain Stimulation (DBS) of the nucleus accumbens and the anterior limb of the internal capsule is performed: Two weeks after DBS implantation, the device is turned on for monopolar stimulation of the nucleus accumbens. It remains activated for 6 weeks (until the 8th week postoperatively) and then turned off. The device is reactivated at the 10th week for monopolar stimulation of the anterior limb of the internal capsule, which is maintained for 6 weeks (until the 16th week postoperatively) before being shut down again. Subsequently, the device is turned on at the 18th week postoperatively for combined stimulation of the nucleus accumbens and the anterior limb of the internal capsule. Efficacy evaluation is conducted after 6 weeks of combined stimulation.

Intervention code：

组别：

试验组2

样本量：

 5

Group：

Group 2

Sample size：

干预措施：

行伏隔核和内囊前肢脑深部电刺激（DBS），DBS植入术后2周后开机进行单纯内囊前肢刺激，开机（6周）至术后第8周后关机，然后第10周开机进行单纯伏隔核刺激，开机（6周）后至第16周关机。随后在术后第18周进行开机，进行伏隔核和内囊前肢联合刺激，联合刺激6周后进行效果评价。

干预措施代码：

Intervention：

Deep Brain Stimulation (DBS) of the nucleus accumbens and the anterior limb of the internal capsule is performed: Two weeks after DBS implantation, the device is turned on for monopolar stimulation of the anterior limb of the internal capsule. It remains activated for 6 weeks (until the 8th week postoperatively) and then turned off. The device is reactivated at the 10th week for monopolar stimulation of the nucleus accumbens, which is maintained for 6 weeks (until the 16th week postoperatively) before being shut down again. Subsequently, the device is turned on at the 18th week postoperatively for combined stimulation of the nucleus accumbens and the anterior limb of the internal capsule. Efficacy evaluation is conducted after 6 weeks of combined stimulation.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 福建 

市(区县)：

  

Country：

China

Province：

Fujian

City：

单位(医院)：

 福建医科大学附属第一医院 

单位级别：

 三甲 

Institution
hospital：

The First Affiliated Hospital of Fujian Medical University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

PANSS总分相较于基线的减分率（20%定义有效与否）

指标类型：

主要指标

Outcome：

The reduction rate of the total PANSS score compared with the baseline, where a 20% reduction defines effectiveness or ineffectiveness

Type：

Primary indicator

测量时间点：

术后24周

测量方法：

DBS 植入术后 24 周 PANSS 总分减分率，超过20%为有效，低于20%为无效

Measure time point of outcome：

24 weeks after surgery

Measure method：

The reduction rate of the total PANSS score 24 weeks after DBS implantation: a rate exceeding 20% is considered effective, and a rate below 20% is deemed ineffective.

指标中文名：

临床总体印象量表-精神分裂症（CGI）评分

指标类型：

次要指标

Outcome：

Clinical Global Impressions Scale - Schizophrenia (CGI) score

Type：

Secondary indicator

测量时间点：

术后24周

测量方法：

Measure time point of outcome：

24 weeks after surgery

Measure method：

指标中文名：

药物剂量

指标类型：

次要指标

Outcome：

Drug dosage

Type：

Secondary indicator

测量时间点：

术后24周

测量方法：

Measure time point of outcome：

24 weeks after surgery

Measure method：

指标中文名：

手术相关感染率

指标类型：

副作用指标

Outcome：

Surgery-related infection rate

Type：

Adverse events

测量时间点：

术后3月内

测量方法：

Measure time point of outcome：

Within 3 months after surgery

Measure method：

指标中文名：

手术相关出血率

指标类型：

副作用指标

Outcome：

Surgery-related bleeding rate

Type：

Adverse events

测量时间点：

术后3月内

测量方法：

Measure time point of outcome：

Within 3 months after surgery

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

无

组织：

无

Sample Name：

None

Tissue：

None

人体标本去向

 其它  

说明

无

Fate of sample：

0thers  

Note：

None

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 55 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）：

CRC将使用SAS软件生成随机分配表。该表将包含连续流水编号的随机数字，依据预设的样本量和分组比例（试验组与对照组的比例为1:1）进行随机化。随机分配表将确保每位参与者在分组时具有相同的机会被分配到试验组或对照组。本研究采用中央随机化方法，确保随机化过程的独立性和客观性。在参与者完成手术后7天内，由负责随机化的研究协调员根据随机分配表中的编号为参与者分配组别。

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

CRC responsible for the study will generate a random allocation table using SAS software. The table will contain sequentially numbered random digits, randomized according to the preset sample size and 1:1 grouping ratio. A central randomization method is adopted to ensure the independence and objectivity of the randomization process. Within 7 days after the participant’s surgery, the research coordinator responsible for randomization will assign the group based on the numbers in the random allocation table.

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：

双盲（对受试者和研究者均隐藏分组）

Blinding：

Double-blind (with grouping concealed from both participants and investigators)

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

否No

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）：

无

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

None

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：

病例报告表（CRF）采用纸质版CRF。CRF表的设计将保证能够搜集所有符合试验方案规定并满足统计分析需求的临床数据。数据的录入由研究者完成，数据应来源与原始记录表和/或实验室检查报告单等原始文件并与原始文件一致，研究中的任何观察、检查结果均应及时、正确、完整、清晰、规范、真实的录入研究记录表中。数据管理员负责对已录入数据进行审核与管理。所有临床数据利用纸质版CRF进行收集和管理，福建医科大学附属第一医院研究负责人拥有本研究资料最高权限。各研究者需准确、及时、完整规范填写病例报告表，并依照标准流程完成知情同意书签署、患者纳入排除、自动随机化以及随访数据的收集等。所有的临床评估及影像学评估结果由独立的数据管理员负责监督保管。数据管理员负责对已录入数据进行审核与管理。对于数据存在的疑问，数据管理员将向研究者发送相应的质疑，研究者对数据管理员发送的质疑及时进行回复，数据管理员必要时可以再质疑。项目负责人每季度召开一次数据质控会议，评估各数据质量并及时做出调整。

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

The Case Report Form (CRF) will be in paper-based format. The design of the CRF will ensure that all clinical data required by the study protocol and necessary for statistical analysis can be collected. Data entry will be performed by investigators. The data shall be derived from source documents such as source records and/or laboratory test reports, and shall be consistent with these source documents. Any observations and test results obtained during the study shall be recorded in the study records in a timely, accurate, complete, clear, standardized, and truthful manner. Data managers are responsible for auditing and managing the entered data. All clinical data will be collected and managed using paper-based CRFs. The principal investigator of the study at The First Affiliated Hospital of Fujian Medical University holds the highest authority over the study data. Each investigator shall fill out the CRF accurately, timely, completely, and standardizedly, and complete the signing of informed consent forms, patient inclusion/exclusion, automatic randomization, and collection of follow-up data in accordance with standard procedures. All clinical assessment and imaging assessment results shall be supervised and stored by independent data managers. For any queries regarding the data, data managers will issue corresponding queries to investigators, who shall respond to these queries promptly. Data managers may issue further queries if necessary. The project leader will convene a data quality control meeting quarterly to assess the quality of various data and make timely adjustments.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

暂未确定/Not yet

注册人：

Name of Registration：

  2025-11-17 09:16:49