ChiCTR2500105121 版本V1.0 版本创建时间2025/06/30 09:45:22 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：

 ChiCTR2500105121 

最近更新日期：

Date of Last Refreshed on：

 2025-06-30 09:45:17 

注册时间：

Date of Registration：

 2025-06-30 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

聚焦超声治疗高级别宫颈鳞状上皮内瘤变临床效果及相关机制研究

Public title：

Research on the Clinical Efficacy and Mechanisms of High-Intensity Focused Ultrasound (HIFU) in Treating High-Grade Cervical Squamous Intraepithelial Lesion (HSIL)

注册题目简写：

English Acronym：

研究课题的正式科学名称：

聚焦超声治疗高级别宫颈鳞状上皮内瘤变临床效果及相关机制研究

Scientific title：

Research on the Clinical Efficacy and Mechanisms of High-Intensity Focused Ultrasound (HIFU) in Treating High-Grade Cervical Squamous Intraepithelial Lesion (HSIL)

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：

陶华 

研究负责人：

陶华 

Applicant：

Tao Hua 

Study leader：

Tao Hua 

申请注册联系人电话：

Applicant telephone：

 +86 135 0772 1112

研究负责人电话：

Study leader's
telephone：

+86 135 0772 1112

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：

 937909873@qq.com

研究负责人电子邮件：

Study leader's E-mail：

 937909873@qq.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：

中国广西壮族自治区柳州市鱼峰区博园大道50号

研究负责人通讯地址：

中国广西壮族自治区柳州市鱼峰区博园大道50号

Applicant address：

No. 50 Boyuan Avenue, Yufeng District, Liuzhou, Guangxi Zhuang Autonomous Region, China

Study leader's address：

No. 50 Boyuan Avenue, Yufeng District, Liuzhou, Guangxi Zhuang Autonomous Region, China

申请注册联系人邮政编码：

Applicant postcode：

 545001

研究负责人邮政编码：

Study leader's postcode：

 545001

申请人所在单位：

广州市妇女儿童医疗中心柳州医院

Applicant's institution：

Guangzhou Women and Children's Medical Center Liuzhou Hospital

研究负责人所在单位：

广州市妇女儿童医疗中心柳州医院

Affiliation of the Leader：

Guangzhou Women and Children's Medical Center Liuzhou Hospital

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：

 快审-科研-2024-099

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：

广州市妇女儿童医疗中心柳州医院医学研究伦理委员会

Name of the ethic committee：

Medical Research Ethics Committee Guangzhou Women and Children's Medical Center Liuzhou Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-02-28 00:00:00

伦理委员会联系人：

张玉

Contact Name of the ethic committee：

Zhang Yu

伦理委员会联系地址：

中国广西壮族自治区柳州市鱼峰区博园大道50号

Contact Address of the ethic committee：

No. 50 Boyuan Avenue, Yufeng District, Liuzhou, Guangxi Zhuang Autonomous Region, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 772 280 4266

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：

广州市妇女儿童医疗中心柳州医院

Primary sponsor：

Guangzhou Women and Children's Medical Center Liuzhou Hospital

研究实施负责（组长）单位地址：

中国广西壮族自治区柳州市鱼峰区博园大道50号

Primary sponsor's address：

No. 50 Boyuan Avenue, Yufeng District, Liuzhou, Guangxi Zhuang Autonomous Region, 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)：

广西壮族自治区

市(区县)：

Country：

China

Province：

Guangxi Zhuang Autonomous Region

City：

单位(医院)：

广州市妇女儿童医疗中心柳州医院

具体地址：

中国广西柳州市鱼峰区博园大道50号

Institution
hospital：

Guangzhou Women and Children's Medical Center Liuzhou Hospital

Address：

No. 50 Boyuan Avenue, Yufeng District, Liuzhou, Guangxi Zhuang Autonomous Region, China

经费或物资来源：

自筹

Source(s) of funding：

Self-raised funds

研究疾病：

高级别宫颈鳞状上皮内瘤变  

Target disease：

High-Grade Cervical Squamous Intraepithelial Lesion (HSIL)

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：

本项目拟通过将聚焦超声技术(FUS)辐照过的HSIL患者的宫颈病变组织立即使用CKC 锥切后进行病理切片检查,以了解切除组织凝固坏死范围及病变残留情况;同时使用FUS 辐照宫颈癌caski 细胞,并与未辐照组进行细胞凋亡率与存活率和 E6/E7 蛋白表达情况的对比,以验证宫颈癌Caski 细胞经FUS 辐照后其细胞线粒体膜破坏-mPTP 孔开放-跨膜电位改变-无法合成ATP-细胞凋亡-无法表达E6/E7 蛋白的细胞凋亡机制,评价FUS 治疗 HSIL 的可行性;同时分别对 HSIL 患者进行聚焦超声(FUS)治疗和冷刀锥切治疗(CKC);比较两组术前及术后三个月、六个月和十二个月的 HPV 含量、HPV 病毒E6/E7 蛋白表达情况及 TCT 情况,以评价聚焦超声治疗 HSIL 的有效性;对两组患者术中的出血量、术后出血时间、宫颈创面愈合天数以及术前术后宫颈长度进行对比,以评价 FUS 治疗 HSIL 的安全性及有效性等一系列研究,探讨 FUS 治疗宫颈高级别鳞状上皮内瘤变(HSIL)的可行性及临床安全性、有效性及诱导病变细胞凋亡机制。  

Objectives of Study：

In this project, the cervical lesion tissue of HSIL patients irradiated with focused ultrasound (FUS) CKC was immediately conized and histopathological sections were performed to understand the coagulation necrosis range and residual lesions of the resected tissue. At the same time, cervical cancer caski cells were exposed to FUS, and the apoptosis rate, survival rate and the expression of E6/E7 protein were compared with the non-irradiated group to verify the mitochondrial membrane damage of cervical cancer Caski cells after FUS irradiation The apoptotic mechanism of pore opening-transmembrane potential change -inability to synthesize ATP -apoptosis -inability to express E6/E7 protein was evaluated to evaluate the feasibility of FUS in the treatment of HSIL. HSIL patients were treated with focused ultrasound (FUS) and cold knife conization (CKC). The HPV content, HPV E6/E7 protein expression and TCT were compared between the two groups before and 3 months, 6 months and 12 months after surgery to evaluate the effectiveness of focused ultrasound in the treatment of HSIL. The intraoperative bleeding volume, postoperative bleeding time, cervical wound healing days, and preoperative and postoperative cervical length were compared between the two groups to evaluate the safety and effectiveness of FUS in the treatment of HSIL To investigate the feasibility, clinical safety, efficacy and apoptosis mechanism of cervical high-grade squamous intraepithelial neoplasia (HSIL).

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、 阴道镜下宫颈转化区为Ⅰ型转化区(完全可见),病变部位范围及边界可完整暴露; 2、宫颈部位活检经病理检查确诊为宫颈 HSIL,且宫颈搔刮(ECC) 阴性; 3、 术前检测高危型HPV 阳性; 4、入组前 3 个月内未接受过其他宫颈手术或物理治疗; 5、对实验内容知情理解知情,并签署知情同意书。

Inclusion criteria

1.The cervical transformation zone is classified as Type I (fully visible) under colposcopy, with the lesion's extent and boundaries completely exposed. 2.Pathological confirmation of cervical HSIL via cervical biopsy, with negative endocervical curettage (ECC) results. 3.High-risk HPV infection confirmed by preoperative testing. 4.No prior cervical surgery or physical therapy within the last 3 months before enrollment. 5.Informed consent obtained, indicating the patient's understanding and voluntary agreement to participate in the study

排除标准：

1.阴道镜下宫颈转化区为Ⅱ-Ⅲ型转化区(部分可见-完全不可见), 病变部位范围及边界不清; 2.宫颈ECC 结果阳性,怀疑宫颈管内病变者; 3.病理诊断可疑宫颈癌或宫颈腺上皮病变者; 4.有宫颈切除史,宫颈鳞状上皮内瘤病变史,盆腔放射治疗史等; 5.合并生殖系统急性炎症,如阴道炎、宫颈炎、外阴炎及盆腔炎等; 6.合并严重内科系统疾病,如心,肝, 肾功能不全,或糖尿病,免疫系统疾病等; 7.妊娠; 8.凝血功能障碍者;

Exclusion criteria：

1.Type II-III cervical transformation zone under colposcopy (partially or completely invisible), with ill-defined lesion margins and extent. 2.Positive ECC (endocervical curettage) results, suggesting possible endocervical involvement. 3.Pathological suspicion of cervical cancer or glandular epithelial lesions. 4.History of cervical excision, cervical squamous intraepithelial lesions, or pelvic radiotherapy. 5.Active genital tract infections, including vaginitis, cervicitis, vulvitis, or pelvic inflammatory disease. 6.Severe systemic diseases, such as cardiac, hepatic, or renal dysfunction, diabetes, or immune disorders. 7.Pregnancy. 8.Coagulation disorders.

研究实施时间：

Study execute time：

从 From 2025-07-10 00:00:00至 To 2028-06-30 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2025-07-10 00:00:00 至 To 2028-06-30 00:00:00

干预措施：

Interventions：

组别：

试验组(FUS治疗组)

样本量：

 89

Group：

Experimental group (FUS treatment group)

Sample size：

干预措施：

术前定位病变区域,按优化参数(如50s/100s/300s)辐照。术后即刻行CKC锥切(仅第一部分研究),病理检查消融效果。

干预措施代码：

Intervention：

Preoperative localization of the lesion area, irradiating according to optimized parameters (such as 50s/100s/300s). Immediately after surgery, perform CKC conization (only for the first part of the study), and conduct pathological examination to assess the ablation effect.

Intervention code：

组别：

对照组(CKC治疗组)

样本量：

 89

Group：

Control group (CKC treatment group)

Sample size：

干预措施：

在患者宫颈病变区域使用FUAS进行定点辐照100秒后进行冷刀锥切

干预措施代码：

Intervention：

Conventional cold-knife conization, with postoperative pathological examination.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 广西壮族自治区 

市(区县)：

 柳州 

Country：

China

Province：

Guangxi Zhuang Autonomous Region

City：

Liuzhou

单位(医院)：

 广州市妇女儿童医疗中心柳州医院 

单位级别：

 三甲 

Institution
hospital：

Guangzhou Women and Children's Medical Center Liuzhou Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

组织消融后凝固坏死面积

指标类型：

主要指标

Outcome：

Coagulation necrosis area post-tissue ablation

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

宫颈癌Caski细胞凋亡率与存活率(流式细胞术)

指标类型：

次要指标

Outcome：

Apoptosis rate and survival rate of cervical cancer Caski cells (flow cytometry)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

术后出血时间

指标类型：

次要指标

Outcome：

Postoperative bleeding time

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：

宫颈组织

组织：

Sample Name：

Cervical Tissue

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 岁 years
最大 Max age 岁 years

性别：

女性

Gender：

Female

随机方法（请说明由何人用什么方法产生随机序列）：

随机分组 使用计算机随机数法将178例参试者分为两组: 实验组(FUS治疗组):89例,接受聚焦超声治疗(辐照时间根据第一部分研究优化)。 对照组(CKC治疗组):89例,接受冷刀锥切术。 治疗流程 FUS组: 术前定位病变区域,按优化参数(如50s/100s/300s)辐照。 术后即刻行CKC锥切(仅第一部分研究),病理检查消融效果。 CKC组:常规冷刀锥切术,术后病理送检。 术中记录 手术时间、出血量(mL)、不良反应(如疼痛、出血)。

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

Randomized Grouping The 178 participants were randomly divided into two groups using a computer-generated random number method: Experimental group (FUS treatment group): 89 cases, receiving focused ultrasound therapy (irradiation time optimized based on the first part of the study). Control group (CKC treatment group): 89 cases, undergoing cold knife conization. Treatment Procedures FUS Group: Preoperative localization of the lesion area, followed by irradiation with optimized parameters (e.g., 50s/100s/300s). Immediate CKC conization post-treatment (only in the first part of the study), with pathological examination to assess ablation efficacy. CKC Group: Standard cold knife conization, with postoperative pathological examination. Intraoperative Records Operation time, blood loss (mL), and adverse reactions (e.g., pain, bleeding).

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

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://cdo.epro-vision.com:81/eproPad/html/index.html，在试验结束6个月内上传试验数据。

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

https://cdo.epro-vision.com:81/eproPad/html/index.html, a period of 6 months at the end of the test to upload the test data.

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：

所有数据待课题完成后6个月内（2028.7.1-2028.12.31）上传至网站（https://cdo.epro-vision.com:81/eproPad/html/index.html）。读者可查阅数据但无权导出。研究人员在提案获批并签署数据访问协议后，可出于研究或监管决策目的获取完整数据权限。所有数据申请均需提交重庆医科大学研究委员会及通讯作者审核，以确认是否存在知识产权或保密义务限制。

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

All data will be uploaded to the website (https://cdo.epro-vision.com:81/eproPad/html/index.html) within 6 months after the completion of the project (from July 1, 2028 to December 31, 2028). Readers can access the data but are not permitted to export it. Researchers can obtain full data access for research or regulatory decision-making purposes after the proposal is approved and a data access agreement is signed. All data requests must be submitted to the Research Committee of Chongqing Medical University and the corresponding author for review to confirm whether there are any intellectual property or confidentiality obligations that may restrict access.

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：

  2025-06-30 09:45:17