ChiCTR2000037906 版本V1.3 版本创建时间2020/11/09 08:34:05 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：

 ChiCTR2000037906 

最近更新日期：

Date of Last Refreshed on：

 2020-11-07 21:58:50 

注册时间：

Date of Registration：

 2020-09-04 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

【辑】延时断食对代谢综合征及衰老相关疾病的防治效果

Public title：

Clinical evaluation in metabolic syndrome and age related disease under prebiotics facilitated continual dietary deprivation

注册题目简写：

延时断食对代谢综合征及衰老相关疾病的生理调节

English Acronym：

Prolonged continual dietary deprivation on Metabolic syndrome and age related diseases

研究课题的正式科学名称：

益生元与电解质辅助下的延时食物剥夺对代谢综合征及衰老相关疾病志愿者生理调节的临床观察

Scientific title：

Clinical evaluation in physical and metabolic improvement in patients with metabolic syndrome and age related diseases under a prebiotics facilitated prolonged continual dietary deprivation

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：

李东航 

研究负责人：

李东航 

Applicant：

Donghang Li 

Study leader：

Garrick D. Lee 

申请注册联系人电话：

Applicant telephone：

 +86 371-22735069

研究负责人电话：

Study leader's
telephone：

+86 13323788731

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：

 Garricklee@foxmail.com

研究负责人电子邮件：

Study leader's E-mail：

 Garricklee@biomed-sci.ac.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：

河南省开封市西门大街357号

研究负责人通讯地址：

河南省开封市西门大街357号

Applicant address：

357 Simon Avenue, Kaifeng, He'nan, China

Study leader's address：

357 Simon Avenue, Kaifeng, He'nan, China

申请注册联系人邮政编码：

Applicant postcode：

 475001

研究负责人邮政编码：

Study leader's postcode：

 475001

申请人所在单位：

河南大学第一附属医院 老年科

Applicant's institution：

Department of Geriatrics Medicine, The First Affiliated Hospital of Henan University

研究负责人所在单位：

河南大学第一附属医院 老年科

Affiliation of the Leader：

Department of Geriatrics Medicine, The First Affiliated Hospital of Henan 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：

 (2019)1201.1

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：

河南大学第一附属医院 医学伦理委员会

Name of the ethic committee：

Medical ethics committee of The First Affiliated Hospital of Henan University

伦理委员会批准日期：

Date of approved by ethic committee：

 2019-12-01 00:00:00

伦理委员会联系人：

牛晨光

Contact Name of the ethic committee：

Chenguang Niu

伦理委员会联系地址：

河南省开封市西门大街357号

Contact Address of the ethic committee：

357 Simon Avenue, Kaifeng, He'nan, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 371-2273 6912

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：

河南大学第一附属医院 老年科

Primary sponsor：

Department of Geriatrics Medicine, The First Affiliated Hospital of Henan University

研究实施负责（组长）单位地址：

河南省开封市西门大街357号

Primary sponsor's address：

357 Simon Avenue, Kaifeng, He'nan, 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)：

河南

市(区县)：

开封

Country：

China

Province：

He'nan

City：

Kaifeng

单位(医院)：

河南大学第一附属医院 老年科

具体地址：

河南省开封市西门大街357号

Institution
hospital：

Department of Geriatrics Medicine, The First Affiliated Hospital of Henan University

Address：

357 Ximen(West Gate) Ave, Kaifeng, Henan

经费或物资来源：

自筹

Source(s) of funding：

From our own money

研究疾病：

代谢综合征、脂肪肝、肌少症  

Target disease：

Metabolic Syndrome、Fatty Liver、and Sarcopenia

研究疾病代码：

C1107，H0314，H0911

Target disease code：

C1107，H0314，H0911

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 治疗新技术临床试验 

Study phase：

New Treatment Measure Clinical Study

研究设计：

历史对照研究 

Study design：

Historical control 

研究目的：

膳食热量限制与剥夺（断食）对不同物种均证实为迄今最强外来干预衰老的延寿手段，而合理断食模式直接涉及衰老最本质机制。我们通过营养细菌的益生元防止因饥饿导致肠道菌群伤害消化道粘膜，辅以电解质缓解饥饿的不适感，已使得数十受试者的50%成功突破14天的持续全断食经历：前7天受试者体重下降明显，6-9天左右饥饿感明显减轻。相对于脂肪持续下降的幅度，体重下降不明显，各项血液指标趋于恢复到断食前水平-转折点（TP），伴随肌酸激酶(CK)与肌肉抑制素(MSTN)的持久性下调，恢复膳食后仍不能像其它生化指标完全回归到断食前水平。这一现象尚未在动物模型中被证实！虽然断食过程中肝功及尿酸血液指标明显上升，但恢复膳食以后均下降到低于断食前水平，多次经历全断食受试者者不仅B超证明消除了肝周围脂肪，整体肝功恢复到正常水平。探讨全断食通过MSTN对脂肪褐变的机制将有助于建立全新生理学概念，并突破脂肪肝防治现有手段。  

Objectives of Study：

Dietary or caloric restriction (DR, or CR) and dietary deprivation (Total fasting DD) in different species have been demonstrated as robust external interventions to increase both median and maximum lifespan. Periodical DD is more practical among human society than long-term DR. However, people usually accepted alternative fasting paradigm as safe issue. Besides, intestinal flora condition has been regarded as more important factors to the health status of human beings. We have designed a combination of natural flora prebiotics and electrolyte to reduce the discomfort in hunger individuals and promoted up to 50% of subjects tested to achieve complete dietary deprivation (CDD) for consequent 14 days with tolerable starving status. We recently found that, after initiated total fasting up to 6~9 days, which depended on individual aspects, subjects’ hunger feeling has been significantly alleviated. Body weight and blood protein have been stabilized while fat related concentration and physical observation have been significantly reduced. We define the CDD 6~9 days as the turning point (TP) which has been the only observed phenomenon in human being. In the same time, the later period of fasting has found significant reduction in blood concentration of creatine kinase and myostatin, and these value remained low even after more than 3 month’s refeeding. This phenomenon indicated that, after the stabilization of ketone metabolism, the initiation of autophagy of the injured tissue in aged individuals might start to transfer in renovating fresh and healthy tissues and stimulate protein anabolism and turnover. Other evident indicated that, repeated administration of fasting led to the recovery of steatohepatitis since liver function criteria turned to be fully recovery. Further approach the mechanism in this model may establish the connection between lipid and protein balance, and will be beneficial in dealing with weight control，and will supply a treatment in adiposis hepatica.

药物成份或治疗方案详述：

在进行“科学断食”两周（十四天）的过程中，采用特殊益生元饮料（成分为植物多糖和膳食纤维）代替一日三餐（每次一袋），避除一切糖类及淀粉类食物来源，并建议尽可能多喝温水，在感觉需要的时候适当补充钾钠镁盐。科学断食进行到7天的时候，需要重复测定断食前同样系列的生理、物理与生化指标，在医生认为身体可以承受及本人有愿望的前提下，继续进行下一个7天的断食体验过程，并在断食结束的当天、2周与2月内再进行同类相关的医学、生理指标的物理和生化检测。同时采集志愿者的血浆、血清、尿液及粪便样品（特别是断食结束以后的第一次大便），部分送往检验科做系统检查，部分分装处理后，于-80℃超低温冰箱中冻存，试验结束后进行血液样品的分子生物学分析及粪便的菌群测序。 样本收集的五个时间点 1）在科学断食开始之前； 2）进行断食一周（第七天）； 3）决定结束断食之前（建议14天，但坚持10天以上的断食过程后才需要接受系统检测并取样本。同时记住收集断食后第一次大便）； 4）断食结束恢复膳食后两周； 5）科学断食结束恢复膳食后二个月 

Description for medicine or protocol of treatment in detail：

The experimental protocol includes oral intake of prebiotics-assisted during continual dietary deprivation (CDD) program. Before the trial starts, the individuals will receive prebiotics herb form (Beijing Cloud Medical International Technology, Inc. China) 10g/bag/person per treatment at three meal times every day during fasting period. The treatment is designed to reduce hunger cravings and sensation at normal meal time. In addition, taking FA daily during fasting is designed to protect the gastrointestinal mucosal from bacteria induced injury under starvation. During the CDD period, subjects are advised to avoid food intake, especially carbohydrates, except drinking plenty of water and keeping constant mineral electrolyte intake and vitamin supply. At the first 3~5 days, to reduce the stress of extreme hunger sensation and craving for food, individuals could consume a few pieces of fruits such as cucumber or tomato. Further taking of additional 1 stick of either 375 mg potassium/400mg magnesium (DAS Gesunde Plus, Deutschland) or 1 pellet of 1.08g (K=10mEq) potassium citrate extended-release tablets (Dawnrays China) every day during extreme hunger periods of day time is suggested to further ameliorate fasting-induced the mineral loss and reduce peristaltic pangs of smooth muscles of the gut. At later periods of fasting, subjects are suggested to consume some tea of American ginseng if one felt in shortage of energy. The routine medical exam during fasting experiment will be scheduled at five time-points by Department of Gerontology of the hospital: 1) before the regimen initiated (control baseline - ad libitum), 2) fasting at 7th day, 3) fasting at 14th day, 4) after recovery with food intake for 7 days, 5) after recovery with food intake within three months. The medical and basic laboratory exams will be performed in The First Affiliated Hospital of Henan University. Stool collection will be scheduled at 3 time points: 1) before fasting, 2) the initial feces after completion of the fasting paradigm, and 3) recovery from fasting for more than a month. The extra serum and plasma samples will be collected and stored under -80oC for future molecular and mechanistic analyses.  

纳入标准：

体重、体重指数、腰围、BMI、心电图、血压（收缩压、舒张压(mmHg)）等来测评是否达到入组要求（填写《问诊表》）, 并确定无器质性病变的21~65岁健康志愿者

Inclusion criteria

Subjects inclusion criteria: (i) volunteers of hospital staffs, including doctors, nurses, lab & med techs et al, and their relatives, (ii) age 21–65 years

排除标准：

有心脏病史及潜在心脏问题（特别是心衰、心梗、心律失常）、肾衰、严重血栓、肠梗阻、妊娠及哺乳期妇女、1型糖尿病导致的胰岛功能完全丧失的患者

Exclusion criteria：

Patients with history of heart disease and potential heart problems (especially heart failure, myocardial infarction, arrhythmia), renal failure, severe thrombosis, intestinal obstruction, pregnant and lactating women, complete loss of islet function caused by type 1 diabetes mellitus

研究实施时间：

Study execute time：

从 From 2020-10-10 00:00:00至 To 2022-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2020-09-20 00:00:00 至 To 2020-12-31 00:00:00

干预措施：

Interventions：

组别：

Case series

样本量：

 50

Group：

Case series

Sample size：

干预措施：

延时膳食剥夺

干预措施代码：

Intervention：

Prolonged Dietary Deprivation

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 河南 

市(区县)：

 开封 

Country：

China

Province：

He'nan

City：

Kaifeng

单位(医院)：

 河南大学第一附属医院 

单位级别：

 三级甲医院 

Institution
hospital：

The First Affiliated Hospital of Henan University

Level of the institution：

Tertiary A hospital

测量指标：

Outcomes：

指标中文名：

临床体检基础指标检测

指标类型：

主要指标

Outcome：

The routine medical exam

Type：

Primary indicator

测量时间点：

方案中的五个时间点

测量方法：

医生检测

Measure time point of outcome：

Five time points of the protocol

Measure method：

Medical Doctor performance

指标中文名：

人体成分分析报告

指标类型：

主要指标

Outcome：

Bioelectrical impedance analysis (BEIA) InBody 720 Body Composition Analyzer

Type：

Primary indicator

测量时间点：

方案中的五个时间点

测量方法：

电子仪器综合测试

Measure time point of outcome：

Five time points of the protocol

Measure method：

Comprehensive test of electronic instruments

指标中文名：

临床化验室生化及常规测试

指标类型：

主要指标

Outcome：

Clinical Laboratory routine and Biochemical tests

Type：

Primary indicator

测量时间点：

方案中的五个时间点

测量方法：

化验室指标

Measure time point of outcome：

Five time points of the protocol

Measure method：

Lab test

指标中文名：

磁共振脂肪定量分析IDEAL-IQ技术

指标类型：

主要指标

Outcome：

Ideal-iq technique for quantitative analysis of fat by magnetic resonance imaging

Type：

Primary indicator

测量时间点：

方案中的五个时间点

测量方法：

质子密度脂肪分数

Measure time point of outcome：

Five time points of the protocol

Measure method：

Proton Density Fat Fraction,PDFF

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

血浆

组织：

Sample Name：

Plasma

Tissue：

人体标本去向

 使用后销毁  

说明

3年

Fate of sample：

Destruction after use  

Note：

3years

标本中文名：

粪便

组织：

Sample Name：

fesis

Tissue：

人体标本去向

 使用后销毁  

说明

3年

Fate of sample：

Destruction after use  

Note：

3years

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 21 岁 years
最大 Max age 65 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）：

首先，断食过程对所有人不是一件容易的事情，需要很多方法帮助其克服恐惧和生理反应，所以受试者在这个干预面前很难有知道使用或者心理暗示的因素。所以，随机方法在这种干预手段面前是没有必要的。 必要点是测试受试者在经历了断食过程以后的一系列生理生化水平的改变，而很多慢性病的不正常状态，往往持续几年，也不是那么容易改变的。 本实验采取自身对照方法： 1. 成功完成3，5, 7，或者14天志愿者，与本人参与前的一系列相关指标进行对比。 如果不能完成或者只能完成短期的断食计划，将被作为对照组进行生理性比较 2. 如果志愿者不能顺利完成断食状态，则其数据用于阴性对照组。

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

First of all, the fasting process is not an easy issue for everybody, and many methods are needed to help the subjects to overcome the fear and physiological reactions. Therefore, it is difficult for the subjects to tell wether the factors of use or psychological suggestion before taking the interventio

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：

Blinding：

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）：

以论文发表方式公开并共享

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

Publish the results and share as requested

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：

数据由课题组分析并储存。病例记录，由医院统一保管

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

The data are analyzed and stored by the project research group. Case records shall be kept by the hospital

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2020-09-04 03:28:23