ChiCTR1900024272 版本V1.0 版本创建时间2019/07/08 20:57:03 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：

 ChiCTR1900024272 

最近更新日期：

Date of Last Refreshed on：

 2019-07-04 18:46:46 

注册时间：

Date of Registration：

 2019-07-04 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

肠道菌群与无痛无汗症的发生与发展的相关性分析

Public title：

Analysis of the relationship between intestinal microflora and the occurrence and development of CIPA

注册题目简写：

English Acronym：

研究课题的正式科学名称：

肠道菌群与无痛无汗症的发生与发展的相关性分析

Scientific title：

Analysis of the relationship between intestinal microflora and the occurrence and development of CIPA

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：

洪一顺 

研究负责人：

张咸伟 

Applicant：

Hong Yishun 

Study leader：

Zhang Xianwei 

申请注册联系人电话：

Applicant telephone：

 +86 15002785828

研究负责人电话：

Study leader's
telephone：

+86 13037154560

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：

 714619450@qq.com

研究负责人电子邮件：

Study leader's E-mail：

 Painfree@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：

湖北武汉市硚口区解放大道1095号

研究负责人通讯地址：

湖北武汉市硚口区解放大道1095号

Applicant address：

1095 Jiefang Avenue, Qiankou District, Wuhan, Hubei

Study leader's address：

1095 Jiefang Avenue, Qiankou District, Wuhan, Hubei

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：

华中科技大学同济医院麻醉科

Applicant's institution：

Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology

研究负责人所在单位：

华中科技大学同济医院麻醉科

Affiliation of the Leader：

Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology

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：

 [2019]伦审字（S914）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：

华中科技大学同济医学院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology

伦理委员会批准日期：

Date of approved by ethic committee：

 2019-04-24 00:00:00

伦理委员会联系人：

陈汇

Contact Name of the ethic committee：

Chen Hui

伦理委员会联系地址：

湖北省武汉市航空路13号同济医学院基础医学院二号教学楼16楼12号办公室

Contact Address of the ethic committee：

Office 12, 16th Floor, Teaching Building 2, School of Basic Medicine, Tongji Medical College, 13 Aviation Road, Wuhan, Hubei, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 027-83691785

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 tongjilunli@163.com

研究实施负责（组长）单位：

华中科技大学同济医院麻醉科

Primary sponsor：

Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology

研究实施负责（组长）单位地址：

湖北武汉市硚口区解放大道1095号

Primary sponsor's address：

1095 Jiefang Avenue, Qiankou District, Wuhan, Hubei

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

湖北

市(区县)：

武汉

Country：

China

Province：

Hu Bei

City：

Wu Han

单位(医院)：

华中科技大学同济医院麻醉科

具体地址：

硚口区解放大道1095号

Institution
hospital：

Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology

Address：

1095 Jiefang Avenue, Qiankou District

经费或物资来源：

萌蒂（中国）制药有限公司

Source(s) of funding：

Menti (China) Pharmaceutical Co., Ltd.

研究疾病：

先天性无痛无汗症  

Target disease：

CIPA

研究疾病代码：

Target disease code：

研究类型：

基础科学研究

Study type：

Basic Science

研究所处阶段：

 探索性研究/预试验 

Study phase：

0

研究设计：

析因分组（即根据危险因素或暴露因素分组） 

Study design：

Factorial 

研究目的：

先天性无痛无汗症（CIPA）（OMIM＃256800），也称为遗传性感觉和自主神经障碍（HSAN）IV型，于1963年首次报道，它是一种罕见的常染色体隐性遗传疾病，由伤害性和交感神经元发育障碍引起，其主要临床特征是先天性对体表和内脏疼痛的刺激完全不敏感，不出汗及反复出现原因不明的发热。该类患者常有自残行为，如反复咬自己手指、嘴唇和舌尖。此外，常出现由于跌倒、烧伤、骨骼和关节骨折而引起的不同程度的创伤，及稀发、湿疹和青光眼等独特的临床特征。 尽管该疾病已在全世界报道，但目前认为CIPA在大多数人群中是罕见且零散的。以色列和日本报告了数十起病例，在巴基斯坦，韩国和马来西亚等国尚有报道。一项日本的流行病学调查显示2009年在日本境内约有130~210名CIPA患者。在中国，自1983年首次报道汉族CIPA患者病例和2010年台湾报道NTRK1基因突变与CIPA相关以来，近数十年尽管相继有CIPA患者被发现，但数量仍较为罕见。截止目前，本研究团队通过不同渠道相继在国内收集到40余例CIPA患者，且对每位患者都建立了相应的病历档案，可进行随访。 目前对CIPA患者的诊断方法主要集中在以下几个方面。一是通过询问病史，若存在不明原因的反复发热，使用解热药物后效果不佳，不存在感染或存在感染但是经过抗感染治疗后仍然发热的患者，同时存在痛觉丧失的患者，可高度怀疑为CIPA，尤其是幼儿（3-6岁）患者。二是根据临床症状判断，对存在反复发热的患者进行体检以及碘-淀粉发汗试验，发生患者在发热的情况下无出汗现象；对患者实施皮下注射组胺后不会出现红斑的患者，存在全身痛觉丧失或者大部分痛觉丧失的患者。三是依据实验室检查诊断，对患者进行发汗试验结果为阴性，实施低丙种球蛋白血症、葡萄糖负荷试验的胰岛素反应较差，实验室检查发现NTRK1基因出现突变的患者可以有效支持CIPA诊断。四是通过病理组织学检查确诊，如对患者进行活检发现皮肤组织结构以及汗腺形态不存在异常，但是周围神经无髓鞘，同时伴随细小有髓鞘纤维出现缺失，在此基础上结合患者的具体表现和实验室检查结果，则可确诊为CIPA。尽管针对CIPA的诊断方式多样化，但目前尚缺乏简便易行的客观诊断指标。 1996年，美国戈登教授在Science上发表了其关于肠道菌群的研究，揭示了人体肠道共生微生物与人类生理机能、代谢及营养之间的关系，特别是揭示了肠道共生微生物对肥胖、发育，以及营养不良等方面的影响，这一研究成果引起了世界各地的科学家对肠道微生物的思考和研究热情。近年来，随着对肠道菌群的深入研究，发现其与消化道疾病、代谢类疾病、免疫类疾病、精神类疾病，以及心血管疾病的发生和发展均相关。大量研究也明确指出通过对肠道微生物的检测可为一些疾病的诊断提供客观依据。此外，根据人体微生物组设计的各种疾病高相关性分子标记物，可用来进行疾病的早期检测，进而早期发现、早期预防和早期干预。 肠道菌群自人类出生脱离母体，就在肠道内定植，我们不禁思考CIPA患者的肠道菌群与正常人相比，或许先天存在差异，而这类差异，极可能用于该疾病的诊断甚至提供靶点治疗。因此，我们期望通过对该类患者肠道菌群的研究，找到CIPA在诊疗方面的新方向。  

Objectives of Study：

Congenital insensitivity to pain with anhidrosis (CIPA) (OMIM#256800), also known as hereditary sensory and autonomic disorder (HSAN) IV, was first reported in 1963. it is a rare autosomal recessive genetic disease. Caused by nociceptive and sympathetic neuronal development disorders, the main clinical features are congenital insensitivity to body surface and visceral pain stimulation, no sweating and recurrent fever of unknown origin. These patients often have self-maiming behavior, such as repeatedly biting their fingers, lips and the tip of the tongue. In addition, there are often varying degrees of trauma caused by falls, burns, bone and joint fractures, and unique clinical features such as sparse hair, eczema and glaucoma. Although the disease has been reported around the world, CIPA is currently considered to be rare and sporadic in most populations. Israel and Japan have reported dozens of cases, including in Pakistan, South Korea and Malaysia. An epidemiological survey in Japan showed that there were about 130 to 210 CIPA patients in Japan in 2009. In China, since the first reported cases of CIPA in the Han nationality in 1983 and the association between NTRK1 gene mutation and CIPA in Taiwan in 2010, the number of CIPA patients has been found in recent decades, but the number is still relatively rare. Up to now, more than 40 CIPA patients have been collected in China through different channels, and each patient has established the corresponding medical records, which can be followed up.
At present, the diagnostic methods of CIPA patients are mainly focused on the following aspects. First, by asking the medical history, if there is recurrent fever of unknown origin, the effect of antipyretic drugs is not good, there is no infection or infection, but still febrile after anti-infective treatment, and there are patients with loss of pain. It is highly suspected to be a patient with CIPA, especially in young children (3 to 6 years old). Second, according to the clinical symptoms, the patients with recurrent fever were examined and iodine-starch sweating test was carried out, and there was no sweating phenomenon in the case of fever. Patients who do not have erythema after subcutaneous injection of histamine have systemic pain loss or most of the pain loss. Third, according to the laboratory examination and diagnosis, the results of sweating test on the patients were negative, and the insulin response of hypogammaglobulinemia and glucose load test was poor. Laboratory examination found that patients with NTRK1 gene mutation can effectively support the diagnosis of CIPA. Fourth, the diagnosis was confirmed by histopathological examination, such as the biopsy of the patients found that the skin tissue structure and sweat gland morphology were not abnormal, but the peripheral nerve was unmyelinated, accompanied by the loss of small myelinated fibers. On this basis, combined with the specific manifestations of patients and laboratory results, it can be diagnosed as CIPA. Although the diagnostic methods of CIPA are diversified, there is still a lack of simple and objective diagnostic indexes.
In 1996, Professor Gordon of the United States published his study on intestinal flora on Science, which revealed the relationship between human intestinal symbiotic microorganisms and human physiological function, metabolism and nutrition, especially the effects of intestinal symbiotic microorganisms on obesity and development. As well as the impact of malnutrition, this research results have aroused the thinking and research enthusiasm of scientists all over the world to intestinal microorganisms. In recent years, with the in-depth study of intestinal flora, it has been found that it is related to the occurrence and development of digestive tract diseases, metabolic diseases, immune diseases, mental diseases and cardiovascular diseases. A large number of studies have also clearly pointed out that the detection of intestinal microorganisms can provide an objective basis for the diagnosis of some diseases. In addition, a variety of disease-related molecular markers designed according to the human microbiome can be used for early detection, early prevention and early intervention.
The intestinal microflora has been colonized in the intestinal tract since the birth of human beings. We can not help thinking that there may be congenital differences between the intestinal microflora of CIPA patients and normal people, and this kind of difference. It is likely to be used in the diagnosis of the disease and even provide target treatment. Therefore, we hope to find a new direction in the diagnosis and treatment of CIPA through the study of intestinal flora of these patients.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

年龄、性别、体重、饮食结构等基本情况相近；健康志愿者需血常规、肝、肾及凝血功能等体检指标正常，既往无手术史；充分了解本次研究的目的和风险并签署知情同意书者。

Inclusion criteria

the basic conditions of age, sex, body weight and diet were similar, and the physical examination indexes such as blood routine, liver, kidney and blood coagulation function of healthy volunteers were normal, and there was no history of operation. Those who fully understand the purpose and risks of this study and sign informed consent.

排除标准：

因依从性差而导致近15天饮食结构差异较大者。

Exclusion criteria：

There were significant differences in dietary structure in the past 15 days due to poor compliance.

研究实施时间：

Study execute time：

从 From 2019-07-10 00:00:00至 To 2020-05-01 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2019-07-10 00:00:00 至 To 2020-05-01 00:00:00

干预措施：

Interventions：

组别：

CIPA组

样本量：

 41

Group：

Group CIPA

Sample size：

干预措施：

指导CIPA患者和健康志愿者近15天饮食结构相近

干预措施代码：

Intervention：

The diet of CIPA patients was similar to that of healthy volunteers for nearly 15 days.

Intervention code：

组别：

健康志愿者组

样本量：

 30

Group：

Group Healthy Volunteers

Sample size：

干预措施：

指导健康志愿者和CIPA患者近15天饮食结构相近

干预措施代码：

Intervention：

The diet of CIPA patients was similar to that of healthy volunteers for nearly 15 days

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 湖北 

市(区县)：

 武汉 

Country：

China

Province：

Hubei

City：

Wuhan

单位(医院)：

 华中科技大学同济医院麻醉科 

单位级别：

 三级甲等 

Institution
hospital：

Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology

Level of the institution：

Tertiary A Hospital

测量指标：

Outcomes：

指标中文名：

粪便菌群差异

指标类型：

主要指标

Outcome：

Fecal flora difference.

Type：

Primary 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：

粪便

组织：

Sample Name：

faeces

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

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 2 岁 years
最大 Max age 22 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）：

不适用

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

N/A

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：

N/A

Blinding：

N/A

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）：

ResMan, http://www.medresman.org

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

ResMan, http://www.medresman.org

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：

ResMan

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

ResMan

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2019-07-04 18:46:46