ChiCTR2400083734 版本V1.0 版本创建时间2024/04/30 16:26:58 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：

 ChiCTR2400083734 

最近更新日期：

Date of Last Refreshed on：

 2024-04-30 16:26:52 

注册时间：

Date of Registration：

 2024-04-30 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

吸入式哮喘药沙丁胺醇对机体产热的调控功能

Public title：

The regulatory function of the inhaled asthma medication Salbutamol on thermogenesis

注册题目简写：

English Acronym：

研究课题的正式科学名称：

吸入式哮喘药沙丁胺醇对机体产热的调控功能

Scientific title：

The regulatory function of the inhaled asthma medication Salbutamol on thermogenesis

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：

姜俊坤 

研究负责人：

栾冰 

Applicant：

Junkun Jiang 

Study leader：

Bing Luan 

申请注册联系人电话：

Applicant telephone：

 +86 198 2181 3596

研究负责人电话：

Study leader's
telephone：

+86 132 6282 5126

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：

 1731099@tongji.edu.cn

研究负责人电子邮件：

Study leader's E-mail：

 bluan@tongji.edu.cn

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：

中国上海市普陀区真南路500号同济大学沪西校区

研究负责人通讯地址：

中国上海市普陀区真南路500号同济大学沪西校区

Applicant address：

Tongji University Huxi Campus, No. 500 Zhen Nan Road, Putuo District, Shanghai, China

Study leader's address：

Tongji University Huxi Campus, No. 500 Zhen Nan Road, Putuo District, Shanghai, 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：

同济大学

Applicant's institution：

Tongji University

研究负责人所在单位：

同济大学

Affiliation of the Leader：

Tongji 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：

 2023tjdxsy045

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：

同济大学科技伦理委员会

Name of the ethic committee：

Tongji University Ethics Committee for Science and Technology

伦理委员会批准日期：

Date of approved by ethic committee：

 2023-09-25 00:00:00

伦理委员会联系人：

朱杰、张箴波

Contact Name of the ethic committee：

Jie Zhu, Zhenbo Zhang

伦理委员会联系地址：

中国上海市普陀区真南路500号同济大学沪西校区

Contact Address of the ethic committee：

Tongji University Huxi Campus, No. 500 Zhen Nan Road, Putuo District, Shanghai, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 21 5103 0441

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：

同济大学

Primary sponsor：

Tongji University

研究实施负责（组长）单位地址：

中国上海市普陀区真南路500号同济大学沪西校区

Primary sponsor's address：

Tongji University Huxi Campus, No. 500 Zhen Nan Road, Putuo District, 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

市(区县)：

普陀区

Country：

China

Province：

Shanghai

City：

Putuo District

单位(医院)：

同济大学

具体地址：

真南路500号

Institution
hospital：

Tongji University

Address：

No. 500 Zhen Nan Road

经费或物资来源：

上海教育发展基金会和上海市教育委员会曙光计划

Source(s) of funding：

Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission

研究疾病：

肥胖  

Target disease：

Obesity

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：

 探索性研究/预试验 

Study phase：

0

研究设计：

单臂 

Study design：

Single arm 

研究目的：

近年来肥胖及其并发症已严重威胁人类健康。鉴于目前针对肥胖治疗的药物较为局限，因此急需发展新药物及治疗手段以减少患者的痛苦。 哺乳动物脂肪组织主要分为储存能量的白色脂肪和消耗能量的棕色脂肪，运动、冷暴露等致使白色脂肪转变为消耗能量的棕色脂肪，此转变过程被称为脂肪组织棕色化。脂肪组织棕色化的发生增加了机体的能量消耗并以热能的形式散失，有效缓解了肥胖的发生，因此脂肪组织棕色化的调控机制成为肥胖治疗的重要潜在靶点。 沙丁胺醇的主要成分是是β2受体激动剂，可通过吸入式作用到气管平滑肌表面的GPCR受体引发支气管扩张从而减轻哮喘症状,该药物已应用于临床治疗支气管哮喘、喘息性支气管炎，I期临床结果显示该药物对人体具有安全性。前期实验结果显示，肺上皮细胞可分泌蛋白因子调控脂肪组织的棕色化过程，该分泌因子的表达受到肺上皮细胞表面GPCR受体信号通路的调控。当我们使用去甲肾上腺素（NE，GPCR受体激动剂）对小鼠吸入式给药物后发现，小鼠的体重发生显著下调，小鼠脂肪组织产热基因mRNA含量以及体温均发生上调。该现象初步揭示，GPCR受体激动剂可能通过肺上皮细胞分泌因子的介导促进脂肪棕色化，增强机体的产热。为此，我们旨通过人体吸入式给药的方法，验证哮喘药沙丁胺醇对脂肪组织棕色化的调控作用，实现哮喘药治疗肥胖的老药新用功能。  

Objectives of Study：

In recent years, obesity and its complications have severely threatened human health. Given the limited medications currently available for treating obesity, there is an urgent need to develop new drugs and treatment methods to alleviate patient suffering. Mammalian adipose tissue is primarily divided into energy-storing white fat and energy-consuming brown fat. Physical exercise and cold exposure can transform white fat into energy-consuming brown fat, a process known as adipose tissue browning. The occurrence of adipose tissue browning increases the body's energy expenditure and dissipates it in the form of heat, effectively mitigating obesity. Therefore, the regulatory mechanism of adipose tissue browning has become an important potential target for obesity treatment. The main component of Salbutamol is a β2 receptor agonist, which can cause bronchodilation by acting on GPCR receptors on the surface of the tracheal smooth muscle through inhalation, thereby alleviating asthma symptoms. This drug has been used in clinical treatment of bronchial asthma and wheezing bronchitis. Phase I clinical results have shown that this drug is safe for humans. Preliminary experimental results have indicated that pulmonary epithelial cells can secrete protein factors that regulate the browning process of adipose tissue, and the expression of this secretory factor is regulated by the GPCR receptor signaling pathway on the surface of pulmonary epithelial cells. When we administered a GPCR receptor agonist, norepinephrine (NE), to mice via inhalation, we observed a significant reduction in mouse weight and an increase in the mRNA content of thermogenic genes in adipose tissue, as well as an increase in body temperature. This phenomenon preliminarily suggests that GPCR receptor agonists may promote fat browning and enhance thermogenesis in the body mediated by secretory factors from pulmonary epithelial cells. Therefore, we aim to verify the regulatory effect of the asthma medication Salbutamol on adipose tissue browning through inhalation in humans, realizing the new use of old asthma medication in treating obesity.

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）年龄20-40周岁，男性以及女性至少各10人； 2）给予药物后，对受试者心率、血压以及血液成分进行检测； 3）无哮喘病史或按照中国“支气管哮喘防治指南（2016年版）”的定义，诊断为支气管哮喘，目前仍处于持续期； 4）在研究的导入期及治疗期间，能够停用研究药物和其它用于治疗哮喘的β受体激动药物（如：吸入式长效β受体激动剂）； 5）同意参加本临床试验并签署书面知情同意书的受试者。

Inclusion criteria

1. Aged 20-40 years, with at least 10 males and 10 females; 2. After administering the drug, the heart rate, blood pressure, and blood components of the subjects will be tested; 3. No history of asthma or diagnosed with bronchial asthma according to the "Chinese Guidelines for the Prevention and Treatment of Bronchial Asthma (2016 Edition)," and currently still in the persistent phase; 4. During the lead-in period and treatment period of the study, able to discontinue the study drug and other beta-receptor agonist medications used for treating asthma (such as inhaled long-acting beta-receptor agonists); 5. Subjects who agree to participate in this clinical trial and sign a written informed consent form.

排除标准：

1）合并有临床意义的重大肺部疾病； 2）合并其他嗜酸性粒细胞升高相关的疾病； 3）对沙丁胺醇药物过敏者； 4）对抛射氟里昂过敏者； 5）心血管功能不全、冠状动脉供血不足、高血压、糖尿病、和甲状腺机能亢进患者； 6）对其他肾上腺素受体激动剂过敏者； 7）妊娠期、哺乳期、或计划近期有生育计划的妇女； 8）患有罕见的遗传性消化系统疾病-半乳糖不耐受症、乳糖酶缺乏或葡萄糖-乳糖酶吸收不良； 9）研究者认为不宜参加试验的其它原因。

Exclusion criteria：

1. Subjects with clinically significant major pulmonary diseases; 2. Subjects with other diseases associated with elevated eosinophil counts; 3. Individuals allergic to Salbutamol; 4. Individuals allergic to fluorocarbons used as propellants; 5. Patients with cardiovascular dysfunction, insufficient coronary artery supply, hypertension, diabetes, and hyperthyroidism; 6. Individuals allergic to other adrenergic receptor agonists; 7. Women who are pregnant, breastfeeding, or planning to become pregnant in the near future; 8.Individuals with rare hereditary digestive system diseases - lactose intolerance, lactase deficiency, or glucose-galactose malabsorption; 9.Other reasons deemed by the researcher as inappropriate for participation in the trial.

研究实施时间：

Study execute time：

从 From 2022-11-01 00:00:00至 To 2025-11-01 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2024-05-01 00:00:00 至 To 2024-09-01 00:00:00

干预措施：

Interventions：

组别：

男性

样本量：

 13

Group：

Male

Sample size：

干预措施：

受试者被要求遵循类似的日常安排，包括饮食时间、休息/活动时间以及运动量，并在实验前一周避免剧烈运动、咖啡因、药物或酒精摄入，以免影响生物节律/生活方式对产热的影响。为了探索沙丁胺醇吸入对人体脂肪产热的影响，每位受试者在温度和湿度控制的房间内处于放松状态，他们坐在直立的姿势中，上身裸露，距离固定在三脚架上的热成像相机一米远，以确保能够视觉化观察到锁骨上方的脂肪组织。所有志愿者在整个测试过程中都被指导保持相对固定的姿势，尽量减少动作，以避免对身体产热造成不必要的影响。参与者在基线成像前需在测试室内适应一小时。基线成像后，受试者吸入沙丁胺醇（100 微克），并在八小时前后使用FLIR系统观察锁骨上方脂肪组织的热成像。

干预措施代码：

Intervention：

The subjects were requested to follow a similar daily schedule, including time of meals, rest/active hours and amounts of exercises, and avoid vigorous exercise, caffeine, drugs or alcohol consumption one week prior to the experiment to avoid impacts of circadian rhythm/life style on thermogenesis. To uncover Albuterol inhalation on adipose thermogenesis in humans, each subject was in a relaxed state within a temperature- and humidity-controlled room, where they were seated in an upright posture with upper body unclothed and one meter away from a thermal imaging camera fixed on a tripod to ensure visualization of the supraclavicular depots. All volunteers were instructed to maintain a relax posture with minimal movement during the whole test procedure to avoid unnecessary influences on body heat production. Participants were acclimated in the test room for one hour prior to baseline imaging. After baseline imaging, Subject inhaled Albuterol (100 μg) and the thermal signatures of supraclavicular depots were visualized with FLIR system before and after eight hours .

Intervention code：

组别：

女性

样本量：

 13

Group：

Female

Sample size：

干预措施：

受试者被要求遵循类似的日常安排，包括饮食时间、休息/活动时间以及运动量，并在实验前一周避免剧烈运动、咖啡因、药物或酒精摄入，以免影响生物节律/生活方式对产热的影响。为了探索沙丁胺醇吸入对人体脂肪产热的影响，每位受试者在温度和湿度控制的房间内处于放松状态，他们坐在直立的姿势中，上身裸露，距离固定在三脚架上的热成像相机一米远，以确保能够视觉化观察到锁骨上方的脂肪组织。所有志愿者在整个测试过程中都被指导保持相对固定的姿势，尽量减少动作，以避免对身体产热造成不必要的影响。参与者在基线成像前需在测试室内适应一小时。基线成像后，受试者吸入沙丁胺醇（100 微克），并在八小时前后使用FLIR系统观察锁骨上方脂肪组织的热成像。

干预措施代码：

Intervention：

The subjects were requested to follow a similar daily schedule, including time of meals, rest/active hours and amounts of exercises, and avoid vigorous exercise, caffeine, drugs or alcohol consumption one week prior to the experiment to avoid impacts of circadian rhythm/life style on thermogenesis. To uncover Albuterol inhalation on adipose thermogenesis in humans, each subject was in a relaxed state within a temperature- and humidity-controlled room, where they were seated in an upright posture with upper body unclothed and one meter away from a thermal imaging camera fixed on a tripod to ensure visualization of the supraclavicular depots. All volunteers were instructed to maintain a relax posture with minimal movement during the whole test procedure to avoid unnecessary influences on body heat production. Participants were acclimated in the test room for one hour prior to baseline imaging. After baseline imaging, Subject inhaled Albuterol (100 μg) and the thermal signatures of supraclavicular depots were visualized with FLIR system before and after eight hours .

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 

市(区县)：

 普陀区 

Country：

China

Province：

Shanghai

City：

Putuo District

单位(医院)：

 同济大学 

单位级别：

 大学 

Institution
hospital：

Tongji University

Level of the institution：

University

测量指标：

Outcomes：

指标中文名：

肩胛骨区域温度

指标类型：

主要指标

Outcome：

Thermal signatures of supraclavicular depots

Type：

Primary indicator

测量时间点：

给药前以及给药后8小时

测量方法：

Measure time point of outcome：

Before administration and 8 hours after administration

Measure method：

指标中文名：

心率

指标类型：

次要指标

Outcome：

Heart rate

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

血压

指标类型：

次要指标

Outcome：

Blood pressure

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

血液成分

指标类型：

次要指标

Outcome：

Blood components

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：

血液样本

组织：

Sample Name：

Blood samples

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 23 岁 years
最大 Max age 30 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）：

无

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

None

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：

Blinding：

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

是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）：

https://www.cell.com/cell/home）

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

https://www.cell.com/cell/home)

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：

病例记录表

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

Case Record Form

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：

  2024-04-30 16:26:52