中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2500108243
最近更新日期： Date of Last Refreshed on：	2025-08-27 09:46:12
注册时间： Date of Registration：	2025-08-27 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	基于代谢组学与微生物组学的天麻素治疗孤独症疗效相关神经炎症、氧化应激及肠道菌群标记物研究
Public title：	A Study on the Neuroinflammatory, Oxidative Stress, and Gut Microbiota Biomarkers Related to the Therapeutic Efficacy of Gastrodin in Autism Spectrum Disorder Based on Metabolomics and Microbiomics
注册题目简写：
English Acronym：
研究课题的正式科学名称：	基于代谢组学与微生物组学的天麻素治疗孤独症疗效相关神经炎症、氧化应激及肠道菌群标记物研究
Scientific title：	A Study on the Neuroinflammatory, Oxidative Stress, and Gut Microbiota Biomarkers Related to the Therapeutic Efficacy of Gastrodin in Autism Spectrum Disorder Based on Metabolomics and Microbiomics
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：	黄浩宇	研究负责人：	黄浩宇
Applicant：	Huang Haoyu	Study leader：	Huang Haoyu
申请注册联系人电话： Applicant telephone：	+86 177 8700 9338	研究负责人电话： Study leader's telephone：	+86 177 8700 9338
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：	345145728@qq.com	研究负责人电子邮件： Study leader's E-mail：	345145728@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：	云南省昆明市西山区前兴路288号	研究负责人通讯地址：	云南省昆明市西山区前兴路288号
Applicant address：	No. 288 Qianxing Road, Xishan District, Kunming City, Yunnan Province, China	Study leader's address：	No. 288 Qianxing Road, Xishan District, Kunming City, Yunnan Province, China
申请注册联系人邮政编码： Applicant postcode：	650034	研究负责人邮政编码： Study leader's postcode：	650034
申请人所在单位：	昆明市儿童医院
Applicant's institution：	Kunming Children's Hospital
研究负责人所在单位：	昆明市儿童医院
Affiliation of the Leader：	Kunming Children's Hospital

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：	2025-03-181-001	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：	昆明市儿童医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of Kunming Children's Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2025-06-24 00:00:00
伦理委员会联系人：	江知洋
Contact Name of the ethic committee：	Jiang Zhiyang
伦理委员会联系地址：	云南省昆明市西山区前兴路288号
Contact Address of the ethic committee：	No. 288 Qianxing Road, Xishan District, Kunming City, Yunnan Province, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 871 6330 9095	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：

昆明市儿童医院

Primary sponsor：

Kunming Children's Hospital

研究实施负责（组长）单位地址：

云南省昆明市西山区前兴路288号

Primary sponsor's address：

No. 288 Qianxing Road, Xishan District, Kunming City, Yunnan Province, 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)：	云南	市(区县)：
Country：	China	Province：	Yunnan	City：
单位(医院)：	昆明市儿童医院	具体地址：	云南省昆明市西山区前兴路288号
Institution hospital：	Kunming Children's Hospital	Address：	No. 288 Qianxing Road, Xishan District, Kunming City, Yunnan Province, China

经费或物资来源：

云南省高层次卫生健康技术人才培养计划

Source(s) of funding：

Yunnan Province High-Level Health and Medical Technology Talent Training Program

研究疾病：

孤独症谱系障碍

Target disease：

Autism spectrum disorder

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：

随机平行对照

Study design：

Parallel

研究目的：

1.探究天麻素治疗孤独症的作用及核心机制：天麻素是否通过“神经炎症-氧化应激-肠道菌群”多靶点协同改善孤独症症状？ 2.进行天麻素疗效个体差异的预测，多维度生物标志物的系统筛选。 3.疗效异质性归因与精准预测模型构建，推动孤独症康复治疗的精准化和个体化。

Objectives of Study：

1.Investigate the therapeutic effects and core mechanisms of gastrodin in treating autism: Does gastrodin improve autism symptoms through the synergistic multi-target modulation of "neuroinflammation-oxidative stress-gut microbiota"? 2.Predict individual differences in the efficacy of gastrodin and systematically screen multi-dimensional biomarkers. 3.Attribute efficacy heterogeneity and construct a precision prediction model to promote personalized and precise rehabilitation therapy for autism

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

排除标准：

①患有其他严重精神疾病；②有代谢性疾病、脑器质性疾病及其他严重躯体疾病史；③严重的失语症、肢体残障或任何其它可能阻碍完成神经心理学评估的因素、拒不配合的患儿；④近2个月内服用过天麻素补充剂；⑤近4周内使用抗生素或益生菌；⑥不能按要求配合治疗等。

Exclusion criteria：

1 Suffering from other severe mental illnesses; 2 Having a history of metabolic diseases, organic brain diseases, or other severe physical illnesses; 3 Children with severe aphasia, physical disabilities, or any other factors that may hinder the completion of neuropsychological assessments, or those who refuse to cooperate; 4 Having taken gastrodin supplements in the past 2 months; 5 Having used antibiotics or probiotics in the past 4 weeks 6 Failing to cooperate with treatment as required, etc.

研究实施时间：

Study execute time：

从 From 2025-01-01 00:00:00至 To 2027-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-09-01 00:00:00 至 To 2027-07-31 00:00:00

干预措施：

Interventions：

组别：	天麻素干预组	样本量：	36
Group：	Gastrodin Intervention Group	Sample size：	36
干预措施：	口服天麻素；行为干预	干预措施代码：
Intervention：	Oral gastrodin; Behavioral intervention	Intervention code：

组别：	对照组	样本量：	36
Group：	Control group	Sample size：	36
干预措施：	行为干预	干预措施代码：
Intervention：	Behavioral intervention	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	云南	市(区县)：
Country：	China	Province：	Yunnan	City：
单位(医院)：	昆明市儿童医院	单位级别：	三甲
Institution hospital：	Kunming Children's Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	孤独症行为	指标类型：	主要指标
Outcome：	autistic behaviors	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	氧化应激指标	指标类型：	次要指标
Outcome：	Oxidative Stress Indicators	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	神经炎症标志物	指标类型：	次要指标
Outcome：	Neuroinflammatory markers	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	微生物组学指标	指标类型：	次要指标
Outcome：	Microbiomics Indicators	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	代谢组学指标	指标类型：	次要指标
Outcome：	Metabolomics Indicators	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	血液	组织：
Sample Name：	blood	Tissue：
人体标本去向	使用后保存	说明
Fate of sample：	Preservation after use	Note：

标本中文名：	粪便	组织：
Sample Name：	fecal	Tissue：
人体标本去向	使用后保存	说明
Fate of sample：	Preservation after use	Note：

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	3	岁 years
最大 Max age	8	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）：

本研究的随机数列由数据管理员采用 SPSS中的“随机数生成” 模块，设定种子数，生成符合研究设计的随机分配序列

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

The random sequence of this study was generated by the data manager using the "Random Number Generation" module in SPSS, with a seed number set to produce a random allocation sequence consistent with the study design.

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：	在该研究中采用双盲法，即研究者、受试者（及家长）均不知晓分组信息（干预组 / 对照组），直至研究结束后揭盲。 1. 干预措施的一致性处理干预组：给予天麻素（如口服制剂）；对照组：给予与天麻素外观（形状、颜色、包装）、剂型、剂量、服用方法完全一致的安慰剂（如不含活性成分的淀粉片）。由第三方机构（如药学部或独立实验室）负责药物 / 安慰剂的制备、包装和编号，确保除第三方外，研究团队和受试者无法通过外观区分两组干预物。 2. 盲底的生成与保管由数据管理员或统计师根据随机序列生成 “药物编号 - 分组” 对应关系（即 “盲底”），并密封于不透光文件袋中，交由独立于研究的第三方（如伦理委员会或药物临床试验机构）保管。盲底需双重加密（物理密封 + 电子备份加密），非紧急情况不得拆阅。 3. 入组与干预实施受试者入组时，研究者按随机号顺序发放对应编号的药物 / 安慰剂（编号仅代表顺序，不体现分组），并指导家长按统一说明给患儿服用（如每日剂量、时间）。研究者、评估者（如量表评分人员）、数据收集者均不参与药物制备和编号，全程不知晓分组信息。 4. 盲态维持与紧急破盲研究期间，所有评估（如 ABC 量表评分、实验室检测）均在盲态下进行，记录数据时仅使用受试者编号，不标注分组。若发生严重不良事件（如严重过敏反应）需明确分组以指导治疗，由研究者填写《紧急破盲申请表》，经研究负责人和伦理委员会批准后，由第三方拆阅对应受试者的盲底信息，记录破盲时间、原因及操作人，并立即通知临床团队。破盲后需单独记录该受试者信息，研究结束时统计破盲例数及原因。 5. 研究结束后的揭盲当所有受试者完成干预、数据收集完毕且数据库锁定后，由统计师向第三方申请揭盲，根据盲底关联分组信息与研究数据，进行统计分析。
Blinding：	Double-blinding is adopted in this study, meaning that neither the researchers, subjects (nor their parents) are aware of the group allocation information (intervention group / control group) until unblinding after the study is completed. 1. Consistent handling of intervention measures - Intervention group: Gastrodin (e.g., oral preparation) is administered; - Control group: A placebo (e.g., starch tablets without active ingredients) that is completely consistent with gastrodin in appearance (shape, color, packaging), dosage form, dosage, and administration method is given. The preparation, packaging, and numbering of drugs/placebos are undertaken by a third-party institution (such as the pharmacy department or an independent laboratory) to ensure that, except for the third party, the research team and subjects cannot distinguish the interventions of the two groups by appearance. 2. Generation and storage of the blind code The data manager or statistician generates the "drug number - group" correspondence (i.e., the "blind code") according to the random sequence, seals it in an opaque file bag, and hands it over to a third party independent of the study (such as the ethics committee or the drug clinical trial institution) for storage. The blind code must be double-encrypted (physical sealing + electronic backup encryption) and shall not be opened in non-emergency situations. 3. Enrollment and implementation of intervention When a subject is enrolled, the researcher distributes the drug/placebo with the corresponding number in the order of random numbers (the number only represents the sequence and does not indicate the group) and guides the parents to administer it to the child according to unified instructions (such as daily dosage and time). Researchers, assessors (such as scale raters), and data collectors do not participate in drug preparation and numbering, and are unaware of the group allocation information throughout the process. 4. Maintenance of blinding and emergency unblinding During the study, all assessments (such as ABC scale scoring, laboratory tests) are conducted under blinded conditions. When recording data, only the subject number is used, and no group is marked. If a serious adverse event (such as a severe allergic reaction) occurs and the group needs to be clarified to guide treatment, the researcher fills out the "Emergency Unblinding Application Form". After approval by the study leader and the ethics committee, the third party will read the blind code information of the corresponding subject, record the time, reason, and operator of unblinding, and immediately notify the clinical team. The information of the subject needs to be recorded separately after unblinding, and the number and reasons for unblinding will be counted at the end of the study. 5. Unblinding after the study After all subjects have completed the intervention, data collection is completed, and the database is locked, the statistician applies to the third party for unblinding. The group information is linked with the research data according to the blind code for statistical analysis.
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

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）：	不共享
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：	一、病例记录表（Case Report Form, CRF）设计内容与模块病例记录表采用结构化纸质版与电子版同步设计，包含以下核心模块：基线信息模块：记录受试者人口学资料（性别、年龄、病程等）、纳入 / 排除标准核查结果、既往病史及用药史（尤其是近 2 个月天麻素补充剂使用史、近 4 周抗生素 / 益生菌使用史）。疗效评估模块：涵盖孤独症核心症状量表（ABC 量表、ADOS-2、CARS 量表）、社会功能量表（VABS 量表）的评分结果，明确填写时间点（基线 T0、治疗 8 周 T1、12 周 T2、随访 24 周 T3）。生物样本信息模块：记录血液（血清 / 血浆）、粪便样本的采集时间、编号、处理过程（如离心条件、冻存温度）、转运记录及实验室检测原始数据（如 IL-6、TNF-α 浓度，代谢组学 / 微生物组学测序原始数据编号）。安全性记录模块：详细记录不良事件（AE）/ 严重不良事件（SAE）的发生时间、表现、处理措施、转归及关联性判断，附研究者签名及日期。干预执行模块：记录天麻素 / 安慰剂的发放剂量、服用依从性（家长每日记录）、剩余药物回收情况，确保干预过程可追溯。填写规范与质控病例记录表由经过培训的研究护士或临床研究员填写，填写前需通过 GCP 及研究方案培训（培训记录存档）。所有数据需及时填写（采集后 24 小时内），字迹清晰、无涂改，修改处需注明日期及修改人签名；电子版 CRF 与纸质版内容需同步核对，确保一致。设立三级核查机制：研究者自查→研究组长抽查（每例数据抽查率≥20%）→数据管理员终查，核查结果记录于《CRF 核查表》，发现问题及时反馈修正。电子采集和管理系统（Electronic Data Capture and Management System）系统选择与功能模块本研究采用符合《药物临床试验质量管理规范（GCP）》要求的电子数据采集系统（如 EpiData、RedCap 或医院自研 EDC 系统），核心功能模块包括：数据录入模块：支持在线录入 CRF 所有字段，设置必填项校验、逻辑校验（如年龄与病程合理性校验）及范围校验（如量表得分区间限制），实时提示数据异常。生物样本关联模块：实现受试者编号与生物样本编号（血液、粪便样本）的一一对应，记录样本采集、转运、检测及存储的全流程时间节点与操作人。权限管理模块：采用分级授权机制，研究者仅可查看本人负责的受试者数据，数据管理员拥有数据审核权限，统计人员仅在数据锁定后获取分析权限，盲态数据（如分组信息）仅第三方保管人员可见。日志追溯模块：自动记录所有数据录入、修改、核查操作的时间、操作人员及具体内容，形成不可篡改的操作日志，确保数据溯源。数据安全与管理流程系统部署于医院内网服务器，采用加密传输（SSL 协议）及定期数据备份（每日自动备份 + 每周异地备份），防止数据丢失或泄露。数据锁定：当所有受试者完成末次随访且 CRF 填写完毕后，由数据管理员发起数据锁定申请，经研究负责人确认后，系统冻结数据录入及修改功能，生成锁定版本号，仅允许读取不可编辑。数据归档：研究结束后，纸质 CRF 经审核后归档至研究中心档案室，电子数据导出为加密文件，连同操作日志、数据核查报告一并存档，保存期限为研究结束后至少 5 年。
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	I. Case Report Form (CRF) Design Content and Modules The CRF is designed in both structured paper and electronic versions, with the following core modules: Baseline Information Module: Records subjects’ demographic data (gender, age, disease duration, etc.), verification results of inclusion/exclusion criteria, past medical history, and medication history (especially gastrodin supplement use in the past 2 months and antibiotic/probiotic use in the past 4 weeks). Efficacy Evaluation Module: Includes scoring results of core autism symptom scales (ABC Scale, ADOS-2, CARS Scale) and social function scales (VABS Scale), with clear documentation of time points (baseline T0, 8 weeks after treatment T1, 12 weeks T2, and 24-week follow-up T3). Biological Sample Information Module: Documents the collection time, numbering, processing procedures (e.g., centrifugation conditions, storage temperature), transportation records, and original laboratory test data (e.g., IL-6, TNF-α concentrations, original sequencing data numbers for metabolomics/microbiomics) of blood (serum/plasma) and fecal samples. Safety Record Module: Details the occurrence time, manifestations, treatment measures, outcomes, and of adverse events (AEs)/serious adverse events (SAEs), with signatures and dates of researchers. Intervention Execution Module: Records the dosage of gastrodin/placebo administered, medication adherence (daily recorded by parents), and recovery of remaining drugs to ensure traceability of the intervention process. Filling Standards and Quality Control CRFs are completed by trained research nurses or clinical researchers, who must pass GCP and study protocol training (training records are archived). All data must be filled in timely (within 24 hours after collection) with clear handwriting and no alterations. Any modifications must be annotated with the date and the modifier’s signature; the electronic CRF must be cross-checked with the paper version to ensure consistency. A three-level verification mechanism is implemented: self-check by researchers → spot check by the research team leader (sampling rate of >= 20% for each case) → final check by the data manager. Verification results are recorded in the CRF Verification Form, and any issues are promptly fed back for correction. II. Electronic Data Capture and Management System System Selection and Functional Modules This study adopts an electronic data capture system compliant with the Good Clinical Practice (GCP) guidelines (e.g., EpiData, RedCap, or the hospital’s self-developed EDC system), with core functional modules including: Data Entry Module: Supports online entry of all CRF fields, with validations for mandatory items, logical checks (e.g., rationality verification of age and disease duration), and range checks (e.g., restriction of scale score intervals), providing real-time prompts for abnormal data. Biological Sample Association Module: Establishes a one-to-one correspondence between subject numbers and biological sample numbers (blood and fecal samples), recording the full-process time nodes and operators of sample collection, transportation, testing, and storage. Permission Management Module: Adopts a hierarchical authorization mechanism: researchers can only view data of subjects under their responsibility; data managers have data review permissions; statisticians can only access data for analysis after data locking; blinded data (e.g., group allocation information) is only visible to third-party custodians. Log Traceability Module: Automatically records the time, operator, and details of all data entry, modification, and verification operations, generating an immutable operation log to ensure data traceability. Data Security and Management Processes The system is deployed on the hospital’s internal server, using encrypted transmission (SSL protocol) and regular data backup (daily automatic backup + weekly off-site backup) to prevent data loss or leakage. Data Locking: After all subjects complete the final follow-up and CRFs are filled, the data manager initiates a data locking application. Upon confirmation by the study leader, the system freezes data entry and modification functions, generates a locked version number, and only allows read access. Data Archiving: After the study is completed, paper CRFs are archived in the research center’s archives after verification. Electronic data is exported as encrypted files, which are archived together with operation logs and data verification reports, with a retention period of at least 5 years after the study ends.
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：	2025-08-27 09:46:07