ChiCTR1900021484 版本V1.1 版本创建时间2019/02/23 11:13:56 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：

 ChiCTR1900021484 

最近更新日期：

Date of Last Refreshed on：

 2019-02-23 11:13:30 

注册时间：

Date of Registration：

 2019-02-23 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

被动音乐治疗对于脑卒中认知功能障碍恢复的临床研究

Public title：

A clinical trial of passive music therapy in the cognitive rehabilitation of stroke patients

注册题目简写：

English Acronym：

研究课题的正式科学名称：

被动音乐治疗对于脑卒中认知功能障碍恢复的临床试验

Scientific title：

A clinical trial of passive music therapy in the cognitive rehabilitation of stroke patients

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：

Luis Alonso Quijano Ruiz 

研究负责人：

詹奕红 

Applicant：

Luis Alonso Quijano Ruiz 

Study leader：

Yihong Zhan 

申请注册联系人电话：

Applicant telephone：

 +86 15396209739

研究负责人电话：

Study leader's
telephone：

+86 136000938842

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：

 aquijanoruiz@gmail.com

研究负责人电子邮件：

Study leader's E-mail：

 yihongzhan31@163.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：

福建省厦门市思明区大学路77号之一403放

研究负责人通讯地址：

福建省厦门市思明区开元街道华菲大厦1702

Applicant address：

77 Daxue Road, Siming District, Xiamen, Fujian, China

Study leader's address：

Huafei Building 1702, Kaiyuan Street, Siming District, Xiamen, Fujian, 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：

厦门大学

Applicant's institution：

Xiamen University

研究负责人所在单位：

厦门大学

Affiliation of the Leader：

Xiamen 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：

 KYH2019-004

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：

厦门大学附属第一医院人体研究伦理委员会

Name of the ethic committee：

Human Research Ethics Committee of Xiamen University

伦理委员会批准日期：

Date of approved by ethic committee：

 2019-01-22 00:00:00

伦理委员会联系人：

石桂秀

Contact Name of the ethic committee：

Guixiu Shi

伦理委员会联系地址：

福建省厦门市镇海路55号

Contact Address of the ethic committee：

55 Zhenhai Road, Siming District, Xiamen, Fujian, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 0592 2137507

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 fhkyb@fh.xmu.edu.cn

研究实施负责（组长）单位：

厦门大学附属第一医院

Primary sponsor：

The First Affiliated Hospital of Xiamen University

研究实施负责（组长）单位地址：

福建省厦门市镇海路55号

Primary sponsor's address：

55 Zhenhai Road, Siming District, Xiamen, Fujian, 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)：

福建

市(区县)：

厦门

Country：

China

Province：

Fujian

City：

Xiamen

单位(医院)：

厦门大学附属第一医院

具体地址：

思明区镇海路55号

Institution
hospital：

The First Affiliated Hospital of Xiamen University

Address：

55 Zhenhai Road, Siming District

经费或物资来源：

厦门大学附属第一医院

Source(s) of funding：

The First Affiliated Hospital of Xiamen University

研究疾病：

那卒中  

Target disease：

Stroke

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：

 其它 

Study phase：

N/A

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

在全球，脑卒中在50岁及以上人群的死因中排名第2位。 70%的脑卒中发生在低中等收入的国家，而且由中风导致的死忙和残疾也发生在这些国家。在中国，2013年抽样调查报告与30年前相比，中国城乡脑卒中患病率均有所增加。而且，这些地区的不当康复服务、不足的预防措施、缺乏脑卒中相关风险的了解会加剧这个情况的恶化。 脑卒中后有 50%—75%的患者会出现认知功能障碍, 脑卒中患者发生认知功能障碍的风险至少是未患脑卒中患者的6—9倍,而且可能持续到数年之后。并且认知功能障碍的发生明显降低患者的生活质量及生存率，有文献报道脑卒中后认知功能障碍非痴呆、脑卒中后痴呆在 1.5 年内的病死率达8%、50%，而 5 年生存率为 75%、39%，所以卒中后认知功能对康复很重要。 脑卒中后认知功能障碍是可以预防和治疗的，音乐聆听可能激活广泛的与注意力、记忆、语义处理、运动功能和情绪处理相关的大脑区域网络。许多临床试验是为了证实音乐聆听对脑卒中认知功能障碍与情绪的影响而被进行的，可是目前可用的研究缺乏统计功效，也更容易产生歧义。因此，我们模拟进行一项研究，以评估音乐治疗是否可以促进脑卒中后认知功能的恢复。  

Objectives of Study：

Stroke is the second leading cause of death worldwide, and 70% of stroke-related deaths and disabilities occur in low- and middle-income countries. Particularly in China, a 2013 report confirmed a rise in the prevalence and incidence of stroke in rural areas compare to data from 30 years ago. This situation is worsened by inadequate rehabilitation services, combined with a lack of preventive measures, and poor understanding of the risks associated with stroke in these regions. 50% - 75% of stroke patients suffer from cognitive disability, which is likely to go on for many years, and the risks of presenting cognitive impairment are six to nine times higher than for those without stroke. Cognitive impairment can cause an evident drop in the quality of life (QOL) of the patient as well as their chances of survival. Corresponding literature suggests that the case fatality rate within 1.5 years after stroke for cognitive-impaired patients with dementia stands at 50%, while it is 8% for those without it. Similarly, five years after stroke, the survival rate stands at 39% for those with dementia, while it is 75% for those without it. Cognitive impairment can be prevented and treated. Listening to music could potentially be used to restore attention, memory, speech, locomotive function, mood, and other brain functions. Several clinical trials have been run to identify the effects of music listening on cognition and mood post-stroke. However, available trials are underpowered and at risk of bias. Therefore, in order to recommend music listening as a treatment for cognitive impairment after stroke, more evidence from clinical trials is needed. This study will be conducted with the goal of providing further evidence on the use of music therapy on treating cognition post-stroke.

药物成份或治疗方案详述：

此研究为双随机对照试验。治疗组将通过聆听选定的音乐从而进行音乐治疗，对照组则聆听白噪音。两组均接受常规的脑卒中治疗，例如拜阿司匹林、立普妥。干预过程如下： 1.b在患者入选研究前，医生将询问、记录患者的病史，并进行 MMSE量表评估、颅脑MR等检查。若患者是合格的纳入者，可自愿参加研究，签署知情同意书。 2. 为了测试音乐素材的情绪反应和偏好之间的差异，在干预之前，患者进行短期音乐类型选择实验。在这个阶段，治疗师会先对招募者进行采访，了解并收集他们的音乐喜好等信息，这些信息将用于治疗组的音乐治疗过程中的音乐列表的创建。对照组虽然使用白噪音（安慰）治疗，不接受上述的音乐治疗，但也会进行音乐喜好的采访，因为这些信息会最终用于统计分析。 3. 所有患者与音乐治疗师单独联系，指导他们每天（每天至少1小时）收听这些素材，患者需要保留听力日记。在为期3个月的时间里，音乐治疗师每周与患者保持密切接触，以鼓励倾听，提供更多音乐素材，并在需要时给予设备使用帮助。 4. 所有患者在干预前、干预后3个月和6个月都进行随访评估。脑卒中量表（NIHSS）、应用简易精神状态量表（MMSE）、蒙特利尔认知评估量表（MoCA）、HAMA焦虑量表、HAMD抑郁量表、护理Zarit量表评估，并且在脑卒中发作后2周内和脑卒中后6个月内进行MRI检查。 

Description for medicine or protocol of treatment in detail：

This study will be a two-arm parallel randomized control trial. Individuals in the treatment group will receive music therapy intervention through preference-based music listening. Individuals in the control group, on the other hand, will receive placebo treatment (white noise). Both groups will also receive, regardless of their allocation, the standard medical treatment for stroke which consists of aspirin and atorvastatin. Details of the intervention process are explained as follows: 1. Before a patient is admitted to the study, a doctor will register the patient's medical history, and carry out the Mini-Mental State Examination (MMSE), the Magnetic Resonance Imaging (MRI) scan, and other specific tests. If the individual meets the eligibility criteria, he/she can opt to participate in the study and sign the informed consent form. 2. Before the intervention starts, in order to examine the emotional response to music, as well as their musical preferences, patients will go through a music selection process. In this stage, therapists will be required to interview recruited patients and gather information on their musical preferences. This information will be used to create the playlist which participants in the treatment group will listen to during the therapy. Although patients in the control group will receive a placebo rather than the aforementioned active treatment, information about their musical preferences should also be gathered, as it will be used for statistical purposes. 3. In this three-month therapy, the music therapists and their corresponding patients and/or their caregivers will maintain close communication. The patients will be encouraged to listen to music every day for at least one hour and requested to fill a listening diary. Therapists will provide any materials if needed, and they will aid their patients and/or caregivers on how to operate the equipment if needed. 4. All the subjects will be assessed before the intervention, as well as three and six months after the intervention. They will be administered the National Institutes of Health Stroke Scale (NIHSS), the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Hamilton Depression Rating Scale (HAMD), and the Zarit burden interview. They will also be administered a Magnetic Resonance Imaging (MRI) scan two weeks and six months after the stroke occurred. 

纳入标准：

1. 年龄50-75岁；
2. 入选前1周内MRI证实急性左或右MCA区域缺血性脑卒中；
3. MMSE≥20分；
4. 既往没有神经或精神疾病、药物或酒精滥用史；
5. 没有严重的听力障碍；
6. 右撇子；
7. 讲普通话，能够合作；
8. 有播放音乐的设备；
9. 有照顾者，能遵守预约就诊、治疗计划等；
10. 患者或家属对治疗方案知情， 自愿接受治疗，并签订知情同意书。

Inclusion criteria

1. Aged 50-75 years;
2. Being within one week after having been administered an MRI scan and been diagnosed ischemic stroke on any of both hemispheres supplied by the middle cerebral artery;
3. MMSE >= 20 points;
4. Not having previous mental disorders or misuse of drugs or alcohol;
5. Not suffering from a serious hearing impairment;
6. Being right-handed;
7. Being willing to communicate and cooperate, and being able to speak Mandarin;
8. Having a music player;
9. Having a caregiver, and being able to commit with the intervention plan and to come to the hospital for the appointments;
10. Being themselves conscious of their condition or having relative aware of the patient's condition, and being willing to undertake the treatment and sign the informed consent form.

排除标准：

1. 其他原因所致的认知功能障碍/痴呆：①意识障碍；②其他神经系统疾病所致的痴呆（如AD等）；③全身性疾病引起的痴呆；④精神疾病（抑郁症等）；
2. 昏迷、精神异常、严重失语、视听严重障碍的患者；
3. 严重抑郁［汉密尔顿抑郁量表( HAMD) 评分≥7 分］ 而影响认知功能评定的患者；
4. 合并全身疾病、肝肾功能严重障碍的患者；
5. 正参加其它临床试验的患者。

Exclusion criteria：

1. Suffering from any other cognitive disabilities or dementia such as impaired consciousness, neurological disorders caused by dementia (e.g., Alzheimer's disease), or any systematic diseases caused by it, and mental disorders like depression;
2. Having a coma, severe aphasia or hearing disability;
3. Suffering from severe depression (HAMD >= 7 points) which could affect the assessment of the cognitive function of the patient;
4. Having severe liver and renal diseases, or any other systemic diseases;
5. Being participating at the same time in a different clinical trial.

研究实施时间：

Study execute time：

从 From 2019-03-01 00:00:00至 To 2019-06-30 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2019-03-01 00:00:00 至 To 2019-03-31 00:00:00

干预措施：

Interventions：

组别：

干预组

样本量：

 30

Group：

Treatment group

Sample size：

干预措施：

音乐聆听

干预措施代码：

Intervention：

Music listening

Intervention code：

组别：

控制组

样本量：

 30

Group：

Control group

Sample size：

干预措施：

一般治疗

干预措施代码：

Intervention：

Treatment as usual

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 福建 

市(区县)：

 厦门 

Country：

China

Province：

Fujian

City：

Xiamen

单位(医院)：

 厦门大学附属第一医院 

单位级别：

 三级甲等 

Institution
hospital：

The First Affiliated Hospital of Xiamen University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

卒中量表

指标类型：

主要指标

Outcome：

National Institutes of Health Stroke Scale (NIHSS)

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

简易精神状态量表

指标类型：

主要指标

Outcome：

Mini-Mental State Examination (MMSE)

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

HAM-A焦虑量表

指标类型：

次要指标

Outcome：

Hamilton Anxiety Rating Scale (HAM-A)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

HAMD抑郁量表

指标类型：

次要指标

Outcome：

Hamilton Depression Rating Scale (HAMD)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

Zarit burden interview

指标类型：

次要指标

Outcome：

Zarit burden interview

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

蒙特利尔认知评估量表（MoCA）

指标类型：

主要指标

Outcome：

Montreal Cognitive Assessment (MoCA)

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：

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 50 岁 years
最大 Max age 75 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）：

由于本研究的样本量较小，为了保证治疗组与对照组受试者人数相等，所以我们采用区组随机化方法。为了确保有效的分配隐藏，将采用带有顺序编号的、不透明的、密封的信封(SNOSE)的方法。当参与者被纳入研究时，将预先编号的信封按顺序打开。 信封内放入复写纸和分配纸，以确保咋在信封上的书写信息的时候可以一并复印在分配纸上。同时，信封内需放入箔纸，用以包裹复印纸和分配纸，确保分配纸上的信息不易泄露。

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

Blocked randomization

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：

该研究为双盲随机对照试验。双盲指在实验中的病人和评估者不知道治疗的性质。因为干预的本质，治疗师的盲法是不可能的。所以，治疗师需要遵守其治疗手册中的治疗方案，以确保治疗组和对照组的患者不会受到不同的治疗。下一节将提供更多的有关致盲方法的信息。

Blinding：

This will be a double-blinded randomized control trial. The term double blinded refers to the patients and the evaluators in the trial being unaware of the nature of the treatment. Due to the nature of the intervention, blinding of the therapists is not possible. However, therapists will need to comply with the treatment protocols stated in their treatment manuals, which will ensure they do not treat patients in the treatment group differently from patients in the control group. More information about the blinding methods is provided in the next section.

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）：

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：

在临床试验中，我们将减少误差和缺失数据的数量，收集尽可能多的数据进行分析，从而提供高质量的数据。为了实现这一目标，将采用最佳实践来确保数据是完整、可靠和正确处理的。 软件：OpenClinica将用于录入和管理数据。它将有助于保持审计跟踪和处理数据差异。“软件验证”将在开始实施前进行，以确保数据安全，因此在转移到真实数据之前，将用于虚拟数据进行测试。 数据收集：数据管理团队将使用OpenClinica设计病例记录表(CRF)。数据字段将被清晰地定义并始终保持一致。CRF为简洁的、不言自明的和用户友好的。由于这是一个电子CRF，出错的机会更少，能够更快的地解决数据差异。 数据录入：如听力日记等纸张的表单，由两名操作员分别录入数据。在录入数据过程中，难以辨认的数据能够引起转录错误和数据差异， 因此录入两次数据有助于验证和核对数据。 数据验证：编辑检查将用于识别录入数据中的差异，这些差异可能是由于不一致的数据或丢失的数据造成的。例如，如果输入患者的MMSE评分为35，软件会自动标记差异错误，因为该测试的最大评分为30。

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

In this clinical trial, high-quality data will be provided by reducing the number of errors and missing data and collecting as much data as possible for analysis. In order to do meet this objective, the best practices will be adopted to ensure that data are complete, reliable, and processed correctly. Software: OpenClinica will be used for registering and managing data. It will help keep an audit trail and deal with data discrepancies. “Software validation” will be conducted to ensure data security before implementation. Entry screens will be tested with dummy data before moving to real data. Data collection: A Case Report Form (CRF) will be designed by the data management team using OpenClinica. The data fields will be clearly defined and be consistent throughout. The CRF will be concise, self-explanatory, and user-friendly. As it will be an electronic CRF, chances of errors are less, and the resolution of discrepancies will be faster. Data entry: As for paper-based forms such as the listening diaries, double data entry will be carried out by two operators separately. This will help in the verification and reconciliation of data by identifying transcription errors and discrepancies caused by illegible data. Data validation: Edit checks will be used to identify discrepancies in the entered data, which could be due to inconsistent data or missing data. For example, if the MMSE score of a patient is entered as 35, a discrepancy error will be flagged automatically by the software as the maximum score of this test is 30.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2019-02-23 11:10:03