ChiCTR2500095112 版本V1.0 版本创建时间2025/01/02 09:33:17 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：

ChiCTR2500095112 

最近更新日期：

Date of Last Refreshed on：

2025-01-02 09:33:09 

注册时间：

Date of Registration：

2025-01-02 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

老年下肢手术患者血清脂联素及脑脊液神经丝轻链蛋白与围术期神经认知障碍的相关性研究

Public title：

Correlation Study of Serum Adiponectin and Cerebrospinal Fluid Neurofilament Light Chain Protein in Elderly Patients Undergoing Lower Extremity Surgery with Perioperative Neurocognitive Disorders

注册题目简写：

English Acronym：

研究课题的正式科学名称：

老年下肢手术患者血清脂联素及脑脊液神经丝轻链蛋白与围术期神经认知障碍的相关性研究

Scientific title：

Correlation Study of Serum Adiponectin and Cerebrospinal Fluid Neurofilament Light Chain Protein in Elderly Patients Undergoing Lower Extremity Surgery with Perioperative Neurocognitive Disorders

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：

陈笑红 

研究负责人：

陈笑红 

Applicant：

Xiaohong Chen 

Study leader：

Xiaohong Chen 

申请注册联系人电话：

Applicant telephone：

+86 136 0026 3882

研究负责人电话：

Study leader's telephone：

+86 136 0026 3882

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：

13929200305@139.com

研究负责人电子邮件：

Study leader's E-mail：

13929200305@139.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：

广东省东莞市万江街道万道路78号 东莞市人民医院麻醉科

研究负责人通讯地址：

广东省东莞市万江街道万道路78号 东莞市人民医院麻醉科

Applicant address：

Department of Anesthesiology, Dongguan People's Hospital, No. 78, Wandao Road, Wanjiang Street, Dongguan City, Guangdong Province

Study leader's address：

Department of Anesthesiology, Dongguan People's Hospital, No. 78, Wandao Road, Wanjiang Street, Dongguan City, Guangdong Province

申请注册联系人邮政编码：

Applicant postcode：

523000

研究负责人邮政编码：

Study leader's postcode：

523000

申请人所在单位：

东莞市人民医院

Applicant's institution：

Dongguan People's Hospital,

研究负责人所在单位：

东莞市人民医院

Affiliation of the Leader：

Dongguan People's Hospital,

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：

KYKT2024-072-A1;KYKT2024-072

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：

东莞市人民医院医学伦理委员会

Name of the ethic committee：

The Medical Ethics Committee of Dongguan People's Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2024-11-18 00:00:00

伦理委员会联系人：

袁领勤

Contact Name of the ethic committee：

Lingqin Yuan

伦理委员会联系地址：

广东省东莞市人民医院硼中子治疗中心一楼 医学伦理委员会办公室

Contact Address of the ethic committee：

Office of the Medical Ethics Committee, on the first floor of the Boron Neutron Therapy Center, Dongguan People's Hospital, Guangdong Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 769 2863 6365

伦理委员会联系人邮箱：

Contact email of the ethic committee：

dgrmyyirb@163.com

研究实施负责（组长）单位：

东莞市人民医院

Primary sponsor：

Dongguan People's Hospital

研究实施负责（组长）单位地址：

广东省东莞市万江街道万道路78号 东莞市人民医院麻醉科

Primary sponsor's address：

Department of Anesthesiology, Dongguan People's Hospital, No. 78, Wandao Road, Wanjiang Street, Dongguan City, Guangdong Province.

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

广东省

市(区县)：

东莞市

Country：

China

Province：

Guangdong Province

City：

Dongguan City

单位(医院)：

东莞市人民医院

具体地址：

广东省东莞市万江街道万道路78号 东莞市人民医院麻醉科

Institution
hospital：

Dongguan People's Hospital

Address：

Department of Anesthesiology, Dongguan People's Hospital, No. 78, Wandao Road, Wanjiang Street, Dongguan City, Guangdong Province.

经费或物资来源：

无

Source(s) of funding：

None

Target disease：

Perioperative Neurocognitive Disorder.

Target disease code：

研究类型：

观察性研究

Study type：

Observational study

研究所处阶段：

 其它 

Study phase：

N/A

研究设计：

横断面 

Study design：

Cross-sectional 

研究目的：

本研究拟围绕在腰硬联合麻醉下行下肢手术的老年患者，探讨其血清APN及脑脊液NfL在围术期的变化特征及其与PND发生的相关性，为PND的预警和早期诊治提供新的依据。  

Objectives of Study：

This study intends to focus on elderly patients undergoing lower extremity surgery under combined spinal-epidural anesthesia, explore the change characteristics of their serum APN and cerebrospinal fluid NfL during the perioperative period and their correlation with the occurrence of PND, and provide a new basis for the early warning, diagnosis and treatment of PND.

药物成份或治疗方案详述：

在签署本知情同意书之后，作为研究的开始，我们将于麻醉前1天对您进行筛选访视。筛选访视旨在了解您是否符合参加本研究的所有要求。如果您不符合要求，您将无法参加本研究。如果您符合要求，并且同意参加本研究，我们将分别于麻醉前5分钟采集静脉血3ml、麻醉中采集脑脊液2ml（常规医疗外的研究性检查）检测外周血所有患者血清脂联素及脑脊液神经丝轻链蛋白水平。在研究前均不使用麻醉前用药，手术前1天采用，在术后1、3 、7d采用简易精神状态量表（MMSE）、国际认知功能障碍研究组推荐的复合Ｚ分法进行认知功能评估，根据评分结果分为PND组（总Z分>=1.96分）与非PND组（总Z分<1.96分）。收集患者各项临床资料，括年龄、性别、体重指数（BMI）、受教育年限、吸烟史和饮酒史以及高血压史、糖尿病史、冠心病史、脑血管意外史等病史资料。所有病史的收集、体格检查、MMSE评分及MoCA评分均由麻醉医师负责完成。 在手术过程中，患者进入手术室后安静仰卧10分钟，开放外周静脉通路输注复方氯化钠注射液。常规监测患者的心率（HR）、血氧饱和度（SpO2）、心电图（ECG）、平均动脉压（MAP）及麻醉深度（BIS），以此作为基础生命体征。麻醉5分钟前采集静脉血3ml。患者侧卧位，通过L3-4间隙进行腰硬联合穿刺。蛛网膜下腔穿刺成功后，留取2ml脑脊液样本，并注射1.5~2.0ml 0.5%的布比卡因作为腰麻药物。血液和脑脊液标本在采集后1小时内处理，3000转/分钟离心10分钟，取上清液置于无菌EP管中，并在-80℃冷冻保存，以供后续实验使用。所取的血清与脑脊液标本均分为两份，一份采用ELISA法分别对血清APN和脑脊液NfL的样本进行检测分析，作为本课题研究所有。另一份留作质谱蛋白组学/代谢组学检测，分析PND/非PND蛋白组学的差异。所有标本送至广州文兴生物科技有限公司，检测完剩余所有标本送回我院，按医疗垃圾无公害销毁。 围术期治疗统一按照医疗常规进行管理，术后采用自控静脉镇痛泵（PCIA泵）进行疼痛控制。静脉镇痛泵舒芬术尼2.0ug/kg、托烷司琼10mg、加生理盐水配至100ml,持续输注48小时，背景输注速率2ml/h,患者疼痛时按压镇痛泵，每次按压的推注容积为2ml，锁定间隔时间30min。术后第1、3、7天，麻醉医师每天在上午9:00-10:00和下午3:00-4:00对患者进行MMSE评分，每天2次。同时，使用视觉模拟评分（VAS）对疼痛进行评估，VAS评分范围为0-10分，分数越低表示疼痛程度越轻。如果术后住院时间小于7天，就在术后第7天及1个月，采用认知功能电话问卷修订版（TICS-M)再次评估您的认知功能。 

Description for medicine or protocol of treatment in detail：

After signing this informed consent form, as the start of the study, we will conduct a screening visit for you 1 day before anesthesia. The screening visit is designed to find out if you meet all the requirements to participate in this study. If you do not meet the requirements, you will not be able to participate in this study. If you meet the requirements and agree to participate in this study, we will collect 3ml of venous blood 5 minutes before anesthesia and 2ml of cerebrospinal fluid during anesthesia (research examination outside of routine medical treatment) to measure the serum levels of adiponectin and cerebrospinal fluid neurofilament light chain protein in peripheral blood of all patients. No pre-anesthesia medication was used before the study, and the cognitive function was assessed 1 day before surgery, and the Mini-Mental State Scale (MMSE) and the composite Z-score method recommended by the International Cognitive Impairment Study Group were used at 1, 3, and 7 days after surgery, and were divided into PND group (total Z score>=1.96 points) and non-PND group (total Z score) according to the scoring results<1.96 points). Various clinical data of the patients were collected, including age, gender, body mass index (BMI), years of education, smoking and alcohol history, hypertension, diabetes, coronary heart disease, cerebrovascular accident and other medical history. All medical history collection, physical examination, MMSE score, and MoCA score are performed by the anesthesiologist. During the operation, the patient was placed on his back quietly for 10 minutes after entering the operating room, and the peripheral venous access was opened for infusion of compound sodium chloride injection. The patient's heart rate (HR), oxygen saturation (SpO2), electrocardiogram (ECG), mean arterial pressure (MAP), and depth of anesthesia (BIS) are routinely monitored as basic vital signs. 3ml of venous blood was collected 5 minutes before anesthesia. The patient is in the lateral decubitus position, and the combined spinal-epidural puncture is performed through the L3-4 space. After the subarachnoid puncture is successful, a 2ml cerebrospinal fluid sample is taken and 1.5~2.0ml of 0.5% bupivacaine is injected as a spinal anesthesia drug. Blood and cerebrospinal fluid specimens were processed within 1 h of collection, centrifuged at 3000 rpm for 10 min, supernatant was placed in sterile EP tubes, and cryopreserved at -80 °C for subsequent experiments. The serum and cerebrospinal fluid samples were divided into two parts, one of which was used by ELISA to detect and analyze the serum APN and cerebrospinal fluid NfL samples, respectively, as the research institute of this project. The other was reserved for mass spectrometry proteomics/metabolomics testing to analyze PND/non-PND proteomics differences. All specimens were sent to Guangzhou Wenxing Biotechnology Co., Ltd., and all the remaining specimens were sent back to our hospital after testing, and destroyed according to the pollution-free medical waste. Perioperative treatment is managed according to medical routine, and self-controlled intravenous analgesia pump (PCIA pump) is used for pain control after surgery. Intravenous analgesic pump sufensel 2.0ug/kg, tropisetron 10mg, plus normal saline to 100ml, continuous infusion for 48 hours, background infusion rate 2ml/h, the patient pressed the analgesic pump when in pain, the bolus volume of each compression was 2ml, and the locking interval was 30min. On the 1st, 3rd, and 7th postoperative days, the anesthesiologist performs MMSE scores on patients at 9:00-10:00 a.m. and 3:00-4:00 p.m. every day, 2 times a day. At the same time, pain is assessed using a visual analogue score (VAS), which ranges from 0 to 10 points, with lower scores indicating less pain. If your hospital stay is less than 7 days postoperative, your cognitive function will be reassessed using the Telephone Questionnaire on Cognitive Function Revised (TICS-M) on day 7 and 1 month after surgery. 

纳入标准：

1.对本次试验的目的和意义有充分了解，自愿参与本次临床试验，并已签署知情同意书； 2.美国麻醉医师协会（ASA）分级为I-III级； 3.择期行下肢手术并需实施腰硬联合麻醉的患者； 4.年龄60岁及以上（含60岁），性别不限； 5.术前MMSE评分文盲>17分，小学>20分，中学或以上>24； 6.近2年无服用镇静药物、抗抑郁药物或其他可能干扰中枢神经系统的药物； 7.无中枢神经系统或精神心理方面的疾病史。

Inclusion criteria

1. Have a full understanding of the purpose and significance of this trial, voluntarily participate in this clinical trial, and have signed the informed consent form; 2. American Society of Anesthesiologists (ASA) grade I-III; 3. Patients who undergo elective lower limb surgery and need to undergo combined spinal-epidural anesthesia; 4. Age 60 and above (including 60 years old), gender is not limited; 5. Preoperative MMSE score for illiterate > 17 points, 20 points for primary school >, and 24 points for middle school or above>; 6. No sedative drugs, antidepressants or other drugs that may interfere with the central nervous system in the past 2 years; 7. No history of central nervous system or psychiatric and psychological diseases.

排除标准：

1.存在椎管内麻醉的禁忌症； 2.可能影响脑脊液中PND生物标志物水平的严重全身性疾病（如恶性肿瘤）； 3.长期使用精神药物、类固醇药物、激素； 4.既往确诊有认知功能障碍病史的患者，及中枢神经系统疾病如多发性硬化、视神经脊髓炎。

Exclusion criteria：

1. Presence of contraindications to neuraxial anesthesia; 2. Severe systemic diseases (such as malignant tumors) that may affect the level of PND biomarkers in cerebrospinal fluid; 3. Long-term use of psychotropic drugs, steroid drugs, hormones; 4. Patients with a history of cognitive dysfunction in the past, and central nervous system diseases such as multiple sclerosis and neuromyelitis optica.

研究实施时间：

Study execute time：

从 From 2024-10-01 00:00:00至 To 2025-10-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2025-01-03 00:00:00 至 To 2025-10-31 00:00:00  

干预措施：

Interventions：

组别：

PND组

样本量：

21

Group：

PND group

Sample size：

干预措施：

无

干预措施代码：

Intervention：

None

Intervention code：

组别：

非PND组

样本量：

61

Group：

Non-PND group

Sample size：

干预措施：

无

干预措施代码：

Intervention：

None

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 广东省 

市(区县)：

 东莞市 

Country：

China 

Province：

Guangdong Province 

City：

Dongguan City 

单位(医院)：

东莞市人民医院 

单位级别：

三级甲等 

Institution
hospital：

Dongguan People's Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

血清脂联素

指标类型：

主要指标

Outcome：

Serum adiponectin

Type：

Primary indicator

测量时间点：

麻醉前

测量方法：

Measure time point of outcome：

before anesthesia

Measure method：

指标中文名：

脑脊液神经丝轻链蛋白

指标类型：

主要指标

Outcome：

Cerebrospinal fluid neurofilament light chain protein

Type：

Primary indicator

测量时间点：

麻醉时

测量方法：

Measure time point of outcome：

During anesthesia

Measure method：

指标中文名：

术前及术后MMSE评分

指标类型：

主要指标

Outcome：

Preoperative and postoperative MMSE scores

Type：

Primary indicator

测量时间点：

术前1天，术后第1.3.7天

测量方法：

按照MMSE评分量表内容对患者进行询问评分

Measure time point of outcome：

One day before the operation, and the 1st, 3rd, and 7th days after the operation

Measure method：

The patients are questioned and scored according to the contents of the MMSE score scale

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：

脑脊液

组织：

Sample Name：

Cerebrospinal fluid

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：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 60 岁 years
最大 Max age 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：

无

Blinding：

None

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：

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：

  2025-01-02 09:33:09