ChiCTR2400086888 版本V1.0 版本创建时间2024/07/15 10:32:55 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：

ChiCTR2400086888 

最近更新日期：

Date of Last Refreshed on：

2024-07-15 10:32:51 

注册时间：

Date of Registration：

2024-07-15 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

基于昼夜节律评价四妙散治疗湿热毒蕴型急性痛风性关节炎的疗效研究

Public title：

Efficacy Study of Si Miao San in the Treatment of Acute Gouty Arthritis with Damp-Heat Toxin Accumulation Pattern based on Circadian Rhythm Evaluation

注册题目简写：

English Acronym：

研究课题的正式科学名称：

基于昼夜节律评价四妙散治疗湿热毒蕴型急性痛风性关节炎的疗效研究

Scientific title：

Efficacy Study of Si Miao San in the Treatment of Acute Gouty Arthritis with Damp-Heat Toxin Accumulation Pattern based on Circadian Rhythm Evaluation

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：

姚静慧 

研究负责人：

姚静慧 

Applicant：

Yao, Jinghui 

Study leader：

Yao, Jinghui 

申请注册联系人电话：

Applicant telephone：

+86 135 6436 9214

研究负责人电话：

Study leader's telephone：

+86 135 6436 9214

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：

zhydyjh@163.com

研究负责人电子邮件：

Study leader's E-mail：

zhydyjh@163.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：

上海市黄浦区普安路185号曙光医院住院部风湿科医生办公室

研究负责人通讯地址：

上海市黄浦区普安路185号曙光医院住院部风湿科医生办公室

Applicant address：

Rheumatology Department Doctors’ Office, Inpatient Ward, Shuguang Hospital, No.185 Pu’an Road, Huangpu District, Shanghai City.

Study leader's address：

Rheumatology Department Doctors’ Office, Inpatient Ward, Shuguang Hospital, No.185 Pu’an Road, Huangpu District, Shanghai City.

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：

上海中医药大学附属曙光医院

Applicant's institution：

Shuguang Hospital affiliated to Shanghai University of T.C.M

研究负责人所在单位：

上海中医药大学附属曙光医院

Affiliation of the Leader：

Shuguang Hospital affiliated to Shanghai University of T.C.M

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：

2023-1397-164

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：

上海中医药大学附属曙光医院伦理委员会

Name of the ethic committee：

IRB of Shuguang Hospital affiliated with Shanghai University of TCM

伦理委员会批准日期：

Date of approved by ethic committee：

2023-12-19 00:00:00

伦理委员会联系人：

耿希

Contact Name of the ethic committee：

Geng Xi

伦理委员会联系地址：

上海市浦东新区张衡路528号

Contact Address of the ethic committee：

No.528,Zhangheng Road,Pudong New Area,Shanghai Pudong New Area

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 21 2025 6070

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：

上海中医药大学附属曙光医院

Primary sponsor：

Shuguang Hospital affiliated to Shanghai University of T.C.M

研究实施负责（组长）单位地址：

上海市张衡路528号

Primary sponsor's address：

528# Zhangheng Rd. Shanghai. 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)：

上海

市(区县)：

Country：

China

Province：

Shanghai

City：

单位(医院)：

上海中医药大学附属曙光医院

具体地址：

上海市张衡路528号

Institution
hospital：

Shuguang Hospital affiliated to Shanghai University of T.C.M

Address：

528# Zhangheng Rd. Shanghai. China

经费或物资来源：

上海市卫健委

Source(s) of funding：

Shanghai Municipal Health Commission

Target disease：

Acute Gouty Arthritis

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 探索性研究/预试验 

Study phase：

0

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

验证四妙散巳时顿服疗效更佳，提高中医药治疗该病的有效率，降低治疗的副作用。  

Objectives of Study：

The purpose of this study is to evaluate the efficacy of Si Miao San in treating acute gouty arthritis of the damp-heat toxin accumulation type, to validate that the therapeutic efficacy of Si Miao San granules is enhanced when taken periodically, with the aim to improve the remission and stability rates of traditional Chinese medicine treatment for this condition and to reduce the side effects of the treatment.

药物成份或治疗方案详述：

两组均保持低盐、低糖、低脂、低嘌呤饮食，防止感染，维持水、电解质及酸碱平衡；控制体重，戒烟酒，避免疲劳和受凉，避免精神紧张和情绪刺激，多饮水。 对照组及试验组均采用四妙散无加减原方颗粒剂（四妙散颗粒）给药，委托江阴天江药业有限公司配制，处方：苍术10g，黄柏12g，生薏苡仁30g，怀牛膝15g。 两组干预措施区别为用药时间不同： 1对照组 四妙散颗粒，按指南及说明书推荐方法服用：每天两次（8：00、17：00），每次1包； 2 试验组 四妙散颗粒，“时辰用药”：每天一次，巳时（9：00至11：00）用药，每次2包。 

Description for medicine or protocol of treatment in detail：

Both groups were required to maintain a low-salt, low-sugar, low-fat, and low-purine diet to prevent infections and maintain water, electrolyte, and acid-base balance. Body weight was controlled, and smoking, alcohol consumption, fatigue, cold exposure, mental tension, and emotional stimulation were avoided. Increased water intake was encouraged. Both, the control group and the experimental group were administered Si Miao San original granules without any modifications (Si Miao San granules), manufactured by Jiangyin Tianjiang Pharmaceutical Co., Ltd. with a prescription of 10g Atractylodes, 12g Phellodendron, 30g Coix seed, and 15g Achyranthes. The intervention measures for the two groups differed by the time of drug administration: Control Group: Taking Si Miao San granules as recommended by the guidelines and instructions: twice daily (at 8:00 and 17:00), one packet each time. Experimental Group: Si Miao San granules are taken "according to the time of day": once daily, during the time of Si (9:00 to 11:00), two packets each time. 

纳入标准：

符合下列全部要求者，方可纳入本次试验。 1）符合2015 年美国风湿病学会（ACR）/欧洲抗风湿联盟（EULAR）制定的痛风诊断标准，及依据《痛风及高尿酸血症中西医结合诊疗指南（2023）》、《中医病证诊断疗效标准》、《中药新药临床研究指导原则》符合祖国传统医学“痛风”“湿热毒蕴证”诊断，且分期属于急性痛风性关节炎期； 2）中医辨证属湿热毒蕴证； 3）18周岁≤年龄≤60周岁，性别不限； 4）自愿参加临床研究并签署知情同意书者。

Inclusion criteria

Only those who meet all the following requirements can be included in this trial. 1)In accordance with the 2015 gout diagnostic criteria established by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR), and based on the "Guidelines for Integrated Traditional Chinese and Western Medicine in the Diagnosis and Treatment of Gout and Hyperuricemia (2023)," the "Standards for Diagnosis and Efficacy of Traditional Chinese Medicine," and the "Guiding Principles for Clinical Research of New Chinese Medicines," the diagnosis aligns with traditional Chinese medicine diagnoses of "gout" and "damp-heat toxin accumulation syndrome," and the stage is classified as acute gouty arthritis. 2)Traditional Chinese medicine distinguishes it as the syndrome of damp-heat and toxin accumulation; 3)Age is between 18 and 60 years old, regardless of gender; 4)Voluntarily participate in clinical research and sign an informed consent form.

排除标准：

具有下列任一情况者，即不纳入本试验。 1）已知对试验药品过敏； 2）已行透析治疗； 3）并发高钾血症、心力衰竭、尿毒症等危及生命的患者； 4）原发病为梗阻性肾病患者； 5）精神性疾病患者； 6）妊娠期或哺乳期妇女； 7）合并脑血管、心血管、肝脏及造血系统等严重原发性疾病者； 8）筛选检查前3个月内行大、中型手术的患者； 9）治疗前2周内服用过其他消炎止痛药物（非甾体类抗炎药、秋水仙碱和糖皮质激素）； 10）入选研究前1个月内服用其他试验药或正在参加其他临床研究。

Exclusion criteria：

Individuals with any of the following conditions will be excluded from this study: 1)Known allergies to the trial drug; 2)Undergoing dialysis treatment; 3)Concurrent hyperkalemia, heart failure, uremia, or other life-threatening conditions; 4)Primary disease being obstructive nephropathy; 5)Mental illness; 6)Pregnant or lactating women; 7)Coexistence of serious primary diseases in the brain, cardiovascular system, liver or hematopoietic system; 8)Undergone major or medium surgery within 3 months prior to the screening examination; 9)Have taken other anti-inflammatory and analgesic drugs (non-steroidal anti-inflammatory drugs, colchicine, and corticosteroids) within 2 weeks before the treatment; 10)Have taken other trial drugs or participating in other clinical studies within 1 month prior to inclusion in the study.

研究实施时间：

Study execute time：

从 From 2024-07-15 00:00:00至 To 2026-07-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2024-07-15 00:00:00 至 To 2026-07-31 00:00:00  

干预措施：

Interventions：

组别：

对照组

样本量：

94

Group：

Control Group

Sample size：

干预措施：

保持低盐、低糖、低脂、低嘌呤饮食，防止感染，维持水、电解质及酸碱平衡。控制体重，戒烟酒，避免疲劳和受凉，避免精神紧张和情绪刺激，多饮水。四妙散无加减原方颗粒剂（四妙散颗粒）给药，委托江阴天江药业有限公司配制，处方：苍术10g，黄柏12g，生薏苡仁30g，怀牛膝15g。按指南及说明书推荐方法服用：每天两次（8：00、17：00），每次1包。

干预措施代码：

Intervention：

Adherence to a diet low in salt, sugar, fat, and purine was necessary, as well as the prevention of infections and maintenance of water, electrolyte, and acid-base balance. Participants were instructed to control their weight, abstain from smoking and alcohol, avoid fatigue and exposure to cold, prevent mental stress and emotional stimuli, and hydrate frequently. The administration of the original formula granules of Simiao San (Simiao San Granules), prepared by Jiangyin Tianjiang Pharmaceuticals Co., Ltd., was implemented. The prescription was: Cangzhu 10g, Huangbo 12g, Raw Coix Seed 30g, Huai Nuxi 15g. According to the guidelines and the instructions, the granules were taken twice a day (at 8:00 and 17:00), one packet each time.

Intervention code：

组别：

试验组

样本量：

94

Group：

Experimental group

Sample size：

干预措施：

保持低盐、低糖、低脂、低嘌呤饮食，防止感染，维持水、电解质及酸碱平衡。控制体重，戒烟酒，避免疲劳和受凉，避免精神紧张和情绪刺激，多饮水。四妙散无加减原方颗粒剂（四妙散颗粒）给药，委托江阴天江药业有限公司配制，处方：苍术10g，黄柏12g，生薏苡仁30g，怀牛膝15g。根据“时辰用药”：每天一次，巳时（9：00至11：00）用药，每次2包。

干预措施代码：

Intervention：

Adherence to a diet low in salt, sugar, fat, and purine was necessary, as well as the prevention of infections and maintenance of water, electrolyte, and acid-base balance. Participants were instructed to control their weight, abstain from smoking and alcohol, avoid fatigue and exposure to cold, prevent mental stress and emotional stimuli, and hydrate frequently. The administration of the original formula granules of Simiao San (Simiao San Granules), prepared by Jiangyin Tianjiang Pharmaceuticals Co., Ltd., was implemented. The prescription was: Cangzhu 10g, Huangbo 12g, Raw Coix Seed 30g, Huai Nuxi 15g. Regarding the granules of Simiao San, "Hora medicating." was employed: once daily, specifically during the ‘Si’ period (between 9:00 and 11:00), with two packets each time.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 上海 

市(区县)：

  

Country：

China 

Province：

Shanghai  

City：

 

单位(医院)：

上海中医药大学附属曙光医院 

单位级别：

三甲 

Institution
hospital：

Shuguang Hospital affiliated to Shanghai University of T.C.M

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

关节疼痛评分

指标类型：

主要指标

Outcome：

Joint Pain Rating

Type：

Primary indicator

测量时间点：

治疗前、连续用7天、14天后

测量方法：

患者自测

Measure time point of outcome：

Before treatment, continuous medication for 7 days, and 14 days.

Measure method：

rated by patient

指标中文名：

关节肿胀评分

指标类型：

次要指标

Outcome：

Joint Swelling Rating

Type：

Secondary indicator

测量时间点：

治疗前、连续用药7天、14天后

测量方法：

研究者评分

Measure time point of outcome：

Before treatment, continuous medication for 7 days, and 14 days.

Measure method：

rated by Investigator

指标中文名：

关节功能评分

指标类型：

次要指标

Outcome：

Joint Function Rating

Type：

Secondary indicator

测量时间点：

治疗前、连续用药7天、14天后

测量方法：

研究者评分

Measure time point of outcome：

Before treatment, continuous medication for 7 days, and 14 days.

Measure method：

rated by Investigator

指标中文名：

中医证候量化积分

指标类型：

次要指标

Outcome：

Quantitative Score of Traditional Chinese Medicine (TCM) Syndrome

Type：

Secondary indicator

测量时间点：

治疗前、连续用药7天、14天后

测量方法：

研究者评分

Measure time point of outcome：

Before treatment, continuous medication for 7 days, and 14 days.

Measure method：

rated by Investigator

指标中文名：

血清C-反应蛋白

指标类型：

次要指标

Outcome：

Serum C-reactive Protein

Type：

Secondary indicator

测量时间点：

治疗前、连续用药14天后

测量方法：

自动生化仪

Measure time point of outcome：

Before treatment and 14 days after continuous medication.

Measure method：

Automated biochemical instrument

指标中文名：

血沉

指标类型：

次要指标

Outcome：

Erythrocyte Sedimentation Rate

Type：

Secondary indicator

测量时间点：

治疗前、连续用药14天后

测量方法：

自动生化仪

Measure time point of outcome：

Before treatment and 14 days after continuous medication.

Measure method：

Automated biochemical instrument

指标中文名：

血尿酸

指标类型：

次要指标

Outcome：

Serum Uric Acid

Type：

Secondary indicator

测量时间点：

治疗前、连续用药14天后

测量方法：

自动生化仪

Measure time point of outcome：

Before treatment and 14 days after continuous medication.

Measure method：

Automated biochemical instrument

指标中文名：

血清Bmal 1蛋白表达量

指标类型：

次要指标

Outcome：

Musculoskeletal Ultrasound Indices

Type：

Secondary indicator

测量时间点：

治疗前、连续用药14天后

测量方法：

自动生化仪

Measure time point of outcome：

Before treatment and 14 days after continuous medication.

Measure method：

Automated biochemical instrument

指标中文名：

白细胞介素-1

指标类型：

次要指标

Outcome：

IL-1

Type：

Secondary indicator

测量时间点：

治疗前、连续用药14天后

测量方法：

自动生化仪

Measure time point of outcome：

Before treatment and 14 days after continuous medication.

Measure method：

Automated biochemical instrument

指标中文名：

白细胞介素-6

指标类型：

次要指标

Outcome：

IL-6

Type：

Secondary indicator

测量时间点：

治疗前、连续用药14天后

测量方法：

自动生化仪

Measure time point of outcome：

Before treatment and 14 days after continuous medication.

Measure method：

Automated biochemical instrument

指标中文名：

肿瘤坏死因子-α

指标类型：

次要指标

Outcome：

TNF-α

Type：

Secondary indicator

测量时间点：

治疗前、连续用药14天后

测量方法：

自动生化仪

Measure time point of outcome：

Before treatment and 14 days after continuous medication.

Measure method：

Automated biochemical instrument

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

血液

组织：

静脉

Sample Name：

Blood

Tissue：

Vein

人体标本去向

 使用后销毁  

说明

使用后销毁

Fate of sample：

Destruction after use  

Note：

Destruction after use.

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 60 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）：

通过 SPSS 25.0 设定随机种子为1000，生成随机数字，根据随机数字大小进行排序，按照1：1的比例分为 2 组，分别为联合用药组与对照组。病例分组通过随机数字制成随机分配卡装入密闭信封，按其进入临床试验的先后次序，拆开号码相同的信封，按信封内卡片规定的编号进行治疗。入组病人按入组时间予受试者编号。

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

Using SPSS 25.0, a random seed of 1000 was set to generate random numbers, which were then sorted according to their size. Based on a 1:1 ratio, subjects were divided into two groups: the combined medication group and the control group. Case grouping was done using random numbers printed on allocation cards, which were enclosed in sealed envelopes. As subjects entered the clinical trial, envelopes with corresponding numbers were opened and treatment was assigned according to the numbers on the cards inside each envelope. Participants were numbered according to the order of their entrance into the study.

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：

本研究计划对结局统计者和数据分析者设盲，不对患者和临床医师设盲。

Blinding：

This study plans to blind the outcome assessors and data analysts, but not the patients and clinical physicians.

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

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：

1 数据库建立及数据录入: 1.1 建立数据库： 根据病例报告表表格的项目采用 EpiData 3.1a 软件建立相应的录入程序，并设定录入时的逻辑审查限定条件，对数据库进行试运行，进而建立本试验专用的数据库系统。 1.2 病例报告表表的进一步检查： 已经审核声明签字的病例报告表表交数据管理员，数据管理员对日期、入组标准、剔除标准、脱落标准、缺失值等进行检查：如有疑问，可填写“数据问题表”，返回监查员，由研究者对疑问表中的问题进行书面解答并签名，交回数据管理员，“数据问题表”应妥善保管。 1.3 数据录入： 由数据管理员进行数据同步录入，采用双人录入法。 1.4 数据审核： 对数据库采用EpiData 3.1a软件中的核查功能进行每一项目的查对，报告不一致的结果值，然后逐项核对原始病例报告表，予以更正，再随机抽取10份病例报告表和数据库中的数据进行人工比较，以确保数据库中的数据与病例报告表中的结果一致。

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

1 Database Establishment and Data Entry: 1.1 Database construction: Based on the items of the case report form, the corresponding entry program is established with EpiData 3.1a software. The logic review limit during entry is set, the database is trial run, and then the database system dedicated to this experiment is established. 1.2 Further examination of the Case Report Form: Case report forms that have been audited and signed a statement are given to the data administrators. The data administrators check the dates, inclusion criteria, exclusion criteria, dropout criteria, and missing values. If there is any doubt, they can fill in the "Data Problem Form" and return it to the investigator. Problems in the question form are responded to, and signed in writing by the researcher, and handed back to the data administrator. The "Data Problem Form" should be properly kept. 1.3 Data entry: Data is synchronously entered by the data administrators, using a double-entry method. 1.4 Data auditing: The database uses the check function in the EpiData 3.1a software to compare each item, report the inconsistent results, then check each original case report form item by item, make corrections, and then randomly select 10 case report forms and data in the database for manual comparison to ensure that the data in the database is consistent with the results in the case report form.

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  2024-07-15 10:32:51