今天是:2019-10-22 星期二

糖基化终产物致糖尿病认知障碍:BDNF-TrkB-CREB信号介导的海马重塑神经网络机制研究
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注册号:

Registration number:

ChiCTR-OCC-15006060 

最近更新日期:

Date of Last Refreshed on:

2019-02-13 

注册时间:

Date of Registration:

2015-03-08 

注册号状态:

补注册  

Registration Status:

Retrospective registration  

注册题目:

糖基化终产物致糖尿病认知障碍:BDNF-TrkB-CREB信号介导的海马重塑神经网络机制研究 

Public title:

Advanced Glycation End Products Induced Cognitive Impairment in Diabetes: BDNF Signal Meditated Hippocampal Neurogenesis 

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

糖基化终产物致糖尿病认知障碍:BDNF-TrkB-CREB信号介导的海马重塑神经网络机制研究 

Scientific title:

Advanced Glycation End Products Induced Cognitive Impairment in Diabetes: BDNF Signal Meditated Hippocampal Neurogenesis 

研究课题代号(代码):

Study subject ID:

国家自然科学基金面上项目 SBE81370921 

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:

王品 

研究负责人:

王少华 

Applicant:

Pin Wang 

Study leader:

Shaohua Wang 

申请注册联系人电话:

Applicant telephone:

+86 18795956236 

研究负责人电话:

Study leader's telephone:

+86 13701581801 

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:

wangpin542@126.com 

研究负责人电子邮件:

Study leader's E-mail:

gyjwsh@126.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:

江苏省南京市丁家桥87号 

研究负责人通讯地址:

江苏省南京市丁家桥87号 

Applicant address:

87 Dingjiaqiao Road, Nanjing, Jiangsu, China 

Study leader's address:

87 Dingjiaqiao Road, Nanjing, Jiangsu, 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:

东南大学附属中大医院 

Applicant's institution:

Affiliated ZhongDa Hospital of Southeast 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:

2013ZDSYLL040.0 

伦理委员会批件附件:

Approved file of Ethical Committee:

批准本研究的伦理委员会名称:

东南大学附属中大医院临床研究伦理委员会 

Name of the ethic committee:

IEC for clinical Research of Zhongda Hospital, Affiliated to Southeast University 

伦理委员会批准日期:

Date of approved by ethic committee:

2013-03-05 

伦理委员会联系人:

 

Contact Name of the ethic committee:

 

伦理委员会联系地址:

 

Contact Address of the ethic committee:

 

伦理委员会联系人电话:

Contact phone of the ethic committee:

 

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:

东南大学附属中大医院 

Primary sponsor:

Affiliated ZhongDa Hospital of Southeast University 

研究实施负责(组长)单位地址:

江苏省南京市丁家桥87号 

Primary sponsor's address:

87 Dingjiaqiao Road, Nanjing, Jiangsu, 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):

江苏

市(区县):

Country:

China

Province:

Jiangsu

City:

单位(医院):

东南大学附属中大医院

具体地址:

江苏省南京市丁家桥87号

Institution
hospital:

Affiliated ZhongDa Hospital of Southeast University

Address:

87 Dingjiaqiao Road, Nanjing, Jiangsu, China

经费或物资来源:

国家自然科学基金面上项目 SBE81370921 

Source(s) of funding:

National Natural Science Foundation of China SBE81370921 

研究疾病:

糖尿病认知障碍 

Target disease:

cognitive decline of diabetes mellitus 

研究疾病代码:

 

Target disease code:

 

研究类型:

病因学/相关因素研究 

Study type:

Cause/Relative factors study 

研究所处阶段:

其它 

Study phase:

N/A 

研究目的:

本研究以AGEs对海马重塑及其神经网络影响为突破口,紧紧围绕AGEs-sRAGE轴,RAGEGly82Ser基因多态性及BDNF-TrkB-CREB信号通路及BDNF(Val66Met)基因多态性,发挥现已有跨学科交叉集成优势,多层面深入探讨AGEs致糖尿病认知障碍的海马重塑神经网络机制, 并联合运用多模态神经影像技术,在体水平进一步揭示其临床功能意义,以期最终发现糖尿病认知障碍的分子和影像学标记,对完善临床诊疗策略进行创建性的探索。 

Objectives of Study:

This study uses the impact of AGEs on remodeling in hippocampal neural networks as an object, focus on AGEs-sRAGE, RAGEGly82Ser gene polymorphism, BDNF-TrkB-CREB signaling pathway and BDNF (Val66Met) polymorphism, play the advantage of cross-disciplinary integration, explore the mechanism of the multiple dimensions of cognitive disorders caused by AGEs hippocampal neural network remodeling, at the same time, using multi-modal neuroimaging techniques to reveal the significance of clinical functional in vivo, hoping to find the biomarkers and molecular imaging markers of diabetes and cognitive impairment. 

药物成份或治疗方案详述:

 

Description for medicine or protocol of treatment in detail:

 

研究设计:

单臂 

Study design:

Single arm 

纳入标准:

(1)糖尿病诊断符合WHO 1999年制订的标准,且明确诊断为2型。 (2)年龄50~75岁。 (3)主诉记忆减退,并经他人证实。 (4)临床痴呆分级量表(Clinical dementia rating,CDR)0.5分。 (5)有足够的视觉和听觉分辨力接受神经心理学测试。 (6)测试前12个月内CT或MRI头颅扫描无感染、梗死或其他局灶性损伤的证据,也无相关临床症状,但允许一个非关键性脑区域的腔隙性梗死且不被认为影响受试者的认知损害。 (7)Hachinski缺血量表(Hachinski ischemia scale,HIS)得分小于或等于4分。 

Inclusion criteria

1. Diabetes diagnosis was formulated in line with WHO 1999 criteria, and a clear diagnosis of type 2; 2. Aged between 50 to 75 years; 3. Complained of memory loss, and confirmed by others; 4. Clinical dementia rating,CDR 0.5; 5. Sufficient visual and auditory resolution to accept neuropsychological tests; 6. No evidence of infection, or other focal infarct damage 12 months prior to the test head CT or MRI scans, and no associated clinical symptoms, but allow a non-critical brain regions without lacunar infarction is thought to affect the test the cognitive impairment; 7. Hachinski ischemia scale(HIS) less than 4. 

排除标准:

(1)近3个月内有糖尿病酮症酸中毒等急性并发症;严重心、肺、肾功能衰竭史;脑血管意外。 (2)任何引起痴呆的神经系统疾病。 (3)既往2年内患抑郁症,汉密尔顿抑郁量表评分>10分。 (4)其他可能导致脑功能紊乱的器质性和精神疾病。 (5)3个月内精神类药物应用史。 

Exclusion criteria:

1. Acute complications such as diabetic ketoacidosis within the past three months; severe heart, lung, kidney failure history; cerebrovascular accident; 2. Any neurological disease caused by dementia; 3. Suffered from depression in past two years, or Hamilton depression scale score> 10 points; 4. Other disorders which possible cause organic brain dysfunction and mental illness; 5. Application of psychotropic drugs in recent three months. 

研究实施时间:

Study execute time:

From2013-03-06To 2024-03-05 

干预措施:

Interventions:

组别:

Case series

样本量:

300

Group:

Case series

Sample size:

干预措施:

Nil

干预措施代码:

Intervention:

Nil

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

江苏 

市(区县):

 

Country:

China 

Province:

Jiangsu 

City:

 

单位(医院):

东南大学附属中大医院 

单位级别:

三甲医院 

Institution
hospital:

Affiliated ZhongDa Hospital of Southeast University  

Level of the institution:

Tertiary A hospital 

测量指标:

Outcomes:

指标中文名:

糖基化终产物

指标类型:

主要指标 

Outcome:

AGEs

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

可溶性糖基化终产物受体

指标类型:

主要指标 

Outcome:

sRAGE

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

脑源性神经营养因子

指标类型:

主要指标 

Outcome:

BDNF

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

RAGE Gly82Ser基因多态性

指标类型:

主要指标 

Outcome:

Polymorphsm of RAGE Gly82Ser

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

BDNF Val66Met基因多态性

指标类型:

主要指标 

Outcome:

Polymorphsm of BDNF Val66Met

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

轻度认知障碍

指标类型:

次要指标 

Outcome:

mild cognitive impairment

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

体质指数

指标类型:

次要指标 

Outcome:

BMI

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

血尿酸

指标类型:

次要指标 

Outcome:

uric acid

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

血胰岛素

指标类型:

次要指标 

Outcome:

insulin

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C肽

指标类型:

次要指标 

Outcome:

c peptide

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

胰岛素样生长因子1

指标类型:

次要指标 

Outcome:

insulin like growth factor-1

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

糖原合酶激酶3β

指标类型:

次要指标 

Outcome:

GSK3 beta

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

β-淀粉样蛋白40

指标类型:

次要指标 

Outcome:

Abeta 40

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

β-淀粉样蛋白42

指标类型:

次要指标 

Outcome:

Abeta 42

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

胰岛素降解酶

指标类型:

次要指标 

Outcome:

Insulin Degrading Enzyme

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

胆固醇酯转运蛋白

指标类型:

次要指标 

Outcome:

cholesteryl ester transfer protein

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

ATP结合盒转运蛋白 A1

指标类型:

次要指标 

Outcome:

ATP-binding cassette transporter A1

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

丛生蛋白

指标类型:

次要指标 

Outcome:

clusterin

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

胱抑素

指标类型:

次要指标 

Outcome:

cystatin

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

早老素蛋白

指标类型:

次要指标 

Outcome:

presenilin

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

血管紧张素转化酶

指标类型:

主要指标 

Outcome:

ACE

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

Lp-PLA2

指标类型:

次要指标 

Outcome:

Lp-PLA2

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

饥饿激素

指标类型:

次要指标 

Outcome:

Ghrelin

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

homocysteine, folate, Vitamin B12, leptin, adiponectin, resistin, visfatin, chemerin, pref-1, cartonectin, rbp-4, apelin, irisin

指标类型:

次要指标 

Outcome:

homocysteine, folate, Vitamin B12, leptin, adiponectin, resistin, visfatin, chemerin, pref-1, cartonectin, rbp-4, apelin, irisin

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

PAI-1, tPA, Aβ40, Aβ42, adipsin, IL-1β

指标类型:

次要指标 

Outcome:

PAI-1, tPA, Aβ40, Aβ42, adipsin, IL-1β

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

RL2 (O-GlcNAc); OGT; OGA; Total tau (Tau-5); p-Tau Ser396 (p-S396); p-Tau Ser404 (p-S404); p-Tau Thr212 (p-T212); p-Tau Thr231 (p-T231)

指标类型:

次要指标 

Outcome:

RL2 (O-GlcNAc); OGT; OGA; Total tau (Tau-5); p-Tau Ser396 (p-S396); p-Tau Ser404 (p-S404); p-Tau Thr212 (p-T212); p-Tau Thr231 (p-T231)

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

BACE1, APOE4, 24-HyCL, CYP46A1, Sirt1, HMG-COAR, CML, INSIG-2 promoter, LPL, FFA, SREBP-1c, chemerin, RARRES2, sLRP1, LRP1

指标类型:

次要指标 

Outcome:

BACE1, APOE4, 24-HyCL, CYP46A1, Sirt1, HMG-COAR, CML, INSIG-2 promoter, LPL, FFA, SREBP-1c, chemerin, RARRES2, sLRP1, LRP1

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

使用后销毁 

说明

Fate of sample:

Destruction after use 

Note:

标本中文名:

尿

组织:

Sample Name:

Urine

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:

结束

Completed

年龄范围:

Participant age:

最小 Min age 50 years
最大 Max age 75 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):

试验员使用随机数字表挑选可能试验对象

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

Test Members may choose to use a random number table test object

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):

原始数据公开时间:

The time of sharing IPD:

即时公开/Real time access

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):

NA

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

NA

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:

NA

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

NA

数据管理委员会:

Data Managemen Committee:

有/Yes

注册人:

Name of Registration:

 2015-03-08
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