ChiCTR2300069465 版本V1.0 版本创建时间2023/03/17 15:50:32 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：

 ChiCTR2300069465 

最近更新日期：

Date of Last Refreshed on：

 2023-03-17 15:50:29 

注册时间：

Date of Registration：

 2023-03-17 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

可再生牙龈替代生物材料在附着龈缺失患者治疗中的临床应用研究

Public title：

To investigate the clinical application of regenerative gingival replacement biomaterials in the treatment of patients with attached gingival loss

注册题目简写：

可再生牙龈替代生物材料的临床应用

English Acronym：

Clinical application of regenerative gingival substitute biomaterials

研究课题的正式科学名称：

可再生牙龈替代生物材料在附着龈缺失患者治疗中的临床应用研究

Scientific title：

To investigate the clinical application of regenerative gingival replacement biomaterials in the treatment of patients with attached gingival loss

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：

徐新月 

研究负责人：

苗辉 

Applicant：

Xinyue Xu 

Study leader：

Hui Miao 

申请注册联系人电话：

Applicant telephone：

 +86 18700912145

研究负责人电话：

Study leader's
telephone：

+86 18291875511

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：

 xinyuexu_1@163.com

研究负责人电子邮件：

Study leader's E-mail：

 miao84776093@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：

陕西省西安市新城区长乐西路169号空军军医大学

研究负责人通讯地址：

陕西省西安市新城区长乐西路169号空军军医大学

Applicant address：

Air Force Medical University, 169 Changle West Road, Xincheng District, Xi 'an, Shaanxi Province, China

Study leader's address：

Air Force Medical University, 169 Changle West Road, Xincheng District, Xi 'an, Shaanxi Province, China

申请注册联系人邮政编码：

Applicant postcode：

 710032

研究负责人邮政编码：

Study leader's postcode：

 710032

申请人所在单位：

中国人民解放军空军军医大学

Applicant's institution：

PLA Air Force Military Medical University

研究负责人所在单位：

中国人民解放军空军军医大学

Affiliation of the Leader：

PLA Air Force Military Medical 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：

 IRB-REV-2022093

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：

中国人民解放军第四军医大学口腔医院医学伦理委员会

Name of the ethic committee：

Medical ethics, Hospital of Stomatology, the Fourth Military Medical University of Chinese PLA

伦理委员会批准日期：

Date of approved by ethic committee：

 2022-08-31 00:00:00

伦理委员会联系人：

王胜朝

Contact Name of the ethic committee：

Sheng-Zhao Wang

伦理委员会联系地址：

陕西省西安市新城区长乐西路145号空军军医大学口腔医院

Contact Address of the ethic committee：

School of Stomatology, Air Force Medical University, 169 Changle West Road, Xincheng District, Xi 'an, Shaanxi Province, China

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：

中国人民解放军空军军医大学

Primary sponsor：

PLA Air Force Medical University

研究实施负责（组长）单位地址：

陕西省西安市新城区长乐西路169号空军军医大学

Primary sponsor's address：

Air Force Medical University, 169 Changle West Road, Xincheng District, Xi 'an, Shaanxi Province, 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)：

陕西

市(区县)：

西安市

Country：

China

Province：

Shaanxi

City：

Xi'an

单位(医院)：

中国人民解放军空军军医大学

具体地址：

陕西省西安市新城区长乐西路169号空军军医大学

Institution
hospital：

PLA Air Force Medical University

Address：

Air Force Medical University, 169 Changle West Road, Xincheng District, Xi 'an, Shaanxi Province, China

经费或物资来源：

国家口腔疾病临床医学研究中心专项课题

Source(s) of funding：

Special project of National Clinical Research Center for Oral Diseases

研究疾病：

牙周疾病  

Target disease：

Periodontal diseases

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：

 治疗新技术临床试验 

Study phase：

New Treatment Measure Clinical Study

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

附着龈是与游离龈相连的角化上皮，其质地坚韧、与骨面附着牢固，角化程度高，因此对于局部刺激有着较好的抵抗力，对于牙周及牙龈健康具有重要意义。然而长期缺牙、外伤或者牙周病等其他原因导致的颌骨重建均会造成附着龈过窄或丧失。附着龈狭窄会破坏局部牙周健康，影响患者的生活质量。因而附着龈增宽术对于减缓患者痛苦，改善临床牙周健康具有重要意义。 目前，对于附着龈缺失的治疗，目前最常用的手术治疗方式是游离龈瓣移植。由于手术效果稳定，愈后效果好，可以广泛用于附着龈缺失患者。但是目前患者自身的游离龈瓣移植术需要两个术区，患者痛苦程度高。此外，自体游离瓣异质性强，收缩程度与瓣的厚度具有相关性，且需要考虑患者供区是否有足够的结缔组织，对于牙龈退缩严重的患者，无法提供足够的结缔组织，限制了这一术式的应用。 考虑到自体游离龈瓣的种种限制，我们将目光转向具有良好生物学性能的、已获得国家相关部门批准、可用于临床患者的牙龈替代生物材料，一种是来源于异体组织的脱细胞真皮基质，一种是可进行人工合成的胶原基质膜。考虑到临床使用的可操作性与方便性，我们拟选取可进行商品化生产的、已上市可供临床应用的AlloDerm SELECT?脱细胞真皮基质和Geistlich Mucograft?胶原基质膜材料进行研究，旨在探索筛选出具有最佳促附着龈再生效果的生物学材料，以期为后续临床治疗提供理论依据。  

Objectives of Study：

Attached gingival is the keratinized epithelium connected to free gingival. It is tough in texture, firmly attached to bone surface, and has a high degree of keratinization. Therefore, it has good resistance to local stimulation, which is of great significance for periodontal and gingival health. However, the attached gingival will be narrow or lost in jaw reconstruction due to long-term tooth loss, trauma or periodontal disease. Attached gingival stenosis can destroy local periodontal health and affect patients' quality of life. Therefore, attached gingival widening is of great significance for relieving patients' pain and improving clinical periodontal health. At present, free gingival flap transplantation is the most commonly used surgical treatment for attached gingival loss. It can be widely used in patients with attached gingival loss due to its stable and good curative effect. However, at present, the patient's own free gingival flap transplantation requires two surgical areas, and the patient has a high degree of pain. In addition, the autogenous free flap is highly heterogeneous, the degree of shrinkage is correlated with the thickness of the flap, and it is necessary to consider whether there is enough connective tissue in the donor area of the patient. For patients with severe gingival retreat, sufficient connective tissue cannot be provided, limiting the application of this procedure. Considering various limitations of autogenous free gingival flap, we turned our attention to gingival substitute biological materials with good biological properties that have been approved by relevant national departments and can be used in clinical patients. One is acellular dermal matrix derived from allogeneic tissue, and the other is collagen matrix membrane that can be synthesized artificially. AlloDerm SELECT? acellular dermal matrix and Geistlich Mucograft? collagen matrix membrane materials that are commercially available and available for clinical use were selected for this study, considering the operability and convenience of clinical use. The aim is to explore and screen out the biological materials with the best effect of promoting attached gingival regeneration, in order to provide theoretical basis for subsequent clinical treatment.

药物成份或治疗方案详述：

①患者纳入：根据纳入排除标准，对于纳入实验的60位角化龈缺失患者进行随机分组，随后根据分组组号，进行手术。 ②具体手术过程： 脱细胞真皮基质组： 术前仔细评估手术牙位、软组织生物型以及牙槽嵴顶正中连线颊侧附着龈宽度或种植体颊侧附着龈宽度。确认无误后局部使用阿替卡因麻醉剂进行浸润麻醉，沿膜龈联合锐性分离做水平切口。随后，向牙根方向分离牙龈形成半厚瓣，向下推向根方，保留骨膜和一部分结缔组织于牙槽骨骨面，缝合固定半厚瓣的边缘，制备一定长度和宽度的受区创面。 将修剪成与创面大小匹配的脱细胞外基质生物材料置于受区结缔组织表面，紧密贴合随后缝合固定，并加压使之与创面进一步贴合，压迫止血。记录创面及异体脱细胞外基质生物材料的长度及宽度。 胶原基质膜组： 术前仔细评估手术牙位、软组织生物型以及牙槽嵴顶正中连线颊侧附着龈宽度或种植体颊侧附着龈宽度。确认无误后局部使用阿替卡因麻醉剂进行浸润麻醉，沿膜龈联合锐性分离做水平切口。随后，向牙根方向分离牙龈形成半厚瓣，向下推向根方，保留骨膜和一部分结缔组织于牙槽骨骨面，缝合固定半厚瓣的边缘，制备一定长度和宽度的受区创面。 将修剪成与创面大小匹配的脱细胞外基质生物材料置于受区结缔组织表面，紧密贴合随后缝合固定，并加压使之与创面进一步贴合，压迫止血。记录创面及异体脱细胞外基质生物材料的长度及宽度。 对照组 自体游离龈瓣制备：局部使用阿替卡因麻醉剂浸润麻醉，根据所需附着龈大小，从患者上颌前磨牙至第一磨牙距龈缘 2-3 mm 的硬腭黏膜处进行取瓣，游离龈瓣的厚度在 1.0-1.5mm 之间，且需修剪去除游离龈瓣上的腺体和脂肪组织。随后将游离龈瓣移植至受区结缔组织表面，紧密贴合随后缝合固定，并加压使之与创面进一步贴合，随后压迫止血。 ③术后护理及用药： 术后嘱咐患者术后使用0.12%醋酸氯己定漱口水进行含漱，用量用法为20mL/次，一日三次，每次1-2分钟。 术后患者可根据自身疼痛情况服用止痛药。推荐使用的止痛药如洛索洛芬钠胶囊，用量用法为饭后服用，60 mg（1粒）/次，一日三次，直至创面及术区不再疼痛。 术后常规口服抗生素，阿莫西林或罗红霉素，阿莫西林用量用法为0.25g/次，一日三次，使用时间持续一周；罗红霉素用量用法150mg/次，一日两次，使用时间持续一周。 ④术后随访 术后2周拆线，回收患者记录出血、水肿、疼痛情况视觉评估表（VAS）以及口服止痛药剂量的问卷表，并拍照。并于术后1月、2月、3月、6月进行复查，记录患者的软组织愈合情况、颊侧附着龈宽、厚度等临床指标，并配合每次使用Aoralscan?3口内扫描仪进行3D口腔检查留取颜色形态等美学指标，拍照留取影像学和口内扫描数字化影像资料。 

Description for medicine or protocol of treatment in detail：

Patient inclusion Based on the inclusion and exclusion criteria, 60 patients with keratinized gingival defects were randomly assigned into experimental groups and underwent surgery according to their group numbers. Specific surgical procedure Decellularized dermal matrix group: Before surgery the surgical site, soft tissue biotype, and attached gingiva width at the buccal side of the alveolar crest or implant were carefully evaluated. After confirming the accuracy, local anesthesia was administered with lidocaine, and a horizontal incision was made along the mucogingival junction. A partial thickness flap was raised towards the root direction and pushed downward, leaving the periosteum and some connective tissue on the alveolar bone surface. The edge of the fixed partial thickness flap was sutured, and a certain size and width of the recipient site wound was prepared. The decellularized extracellular matrix biomaterial, which was trimmed to match the size of the wound was placed on the surface of the connective tissue at the recipient site, closely adhered and sutured, and compressed to further fit the wound and stop bleeding. The length and width of the wound and allogeneic decellularized extracellular matrix biomaterial were recorded. Collagen matrix membrane group: The same procedure as above was performed. Control group: Autogenous free gingival grafts were prepared by infiltrating local anesthesia with lidocaine, and a graft was harvested from the hard palate mucosa 2-3 mm from the gingival margin between the maxillary premolars and first molars according to the required attached gingival size. The thickness of the free gingival graft was between 1.0-1.5 mm, and the glandular and adipose tissues on the graft were trimmed. The free gingival graft was then transplanted onto the surface of the connective tissue at the recipient site closely adhered and sutured and compressed to further fit the wound and stop bleeding. Postoperative care and medication After surgery, patients were instructed to use 0.12% chlorhexidine gluconate mouthwash for rinsing, with a dosage of 20 mL per use, three times a day for 1-2 minutes per use. After surgery patients can take painkillers according to their own pain situation. The recommended painkiller is lornoxicam sodium capsule, to be taken after meals, 60 mg (1 capsule) per time, three times a day, until the wound and surgical area are no longer painful. Antibiotics are routinely taken orally after surgery, with amoxicillin or erythromycin recommended. Amoxicillin should be taken at a dosage of 0.25g per time, three times a day, for one week; erythromycin should be taken at a dosage of 150mg per time, twice a day, for one week. Follow-up visits should be conducted after surgery. At the two-week mark the stitches are removed and patients are asked to complete a questionnaire on bleeding, swelling, pain using a visual analog scale (VAS), and the dosage of oral painkillers taken. Photos are also taken. Follow-up appointments should be scheduled for one, two, three, and six months after surgery, during which the patient's soft tissue healing, buccal attachment width, thickness, and other clinical indicators should be recorded. Aoralscan 3 intraoral scanner should be used for 3D oral examination to collect aesthetic indicators such as color and shape, and photographs and digital images of intraoral scans should be taken. 

纳入标准：

①患者年龄在 25-50 岁之间
②附着龈退缩宽度大于或等于 2 mm
③无明显错颌畸形
④能保持良好口腔卫生的患者
⑤无影响牙周病病程全身性疾病患者
⑥系带未见异常附着
⑦12 个月内未行牙周手术者、

Inclusion criteria

① Patients are aged between 25 and 50 years old
② The width of attached gingival retraction is greater than or equal to 2 mm
③ No obvious malocclusion
④ Patients who can maintain good oral hygiene
⑤ No systemic diseases affecting the course of periodontal disease
⑥ No abnormal attachment was found in the frenulum
⑦ no periodontal operation within 12 months,

排除标准：

①有牙根表面修复无法获得正常附着
②需要修复的牙根龋
③重度吸烟者（>10 根每天）
④有影响牙周病病程的全身性疾病[如糖尿病、高血压、放疗史或癌症治疗史， 例如有肝、肾、造血系统等严重原发性疾病者，或肝功能异常，AST、ALT 大于正常值 1.5/2 倍，肌酐大于正常值上限者；精神病患者；肿瘤患者，预期生命＜6 个月；肾功能不全患者（血肌酐、尿素氮超过正常值范围的 1.2 倍）有免疫缺陷病史，包括 HIV 检测阳性或患有其它获得性、先天性免疫缺陷疾病，或有器官移植史者；]
⑤对麻药等药物过敏
⑥怀孕或哺乳期的女性
⑦因各种原因拒绝参加本项临床研究者
⑧研究中心职员或研究者的伴侣或一级亲属
⑨研究者认为不适合入选的其他情况

Exclusion criteria：

① The root surface of the tooth can not obtain normal attachment
② Root caries that need to be repaired
③ Heavy smokers (> 10 sticks per day)
④ Systemic diseases affecting the course of periodontal disease [such as diabetes, hypertension, radiotherapy history or cancer treatment history, such as liver, kidney, hematopoietic system and other serious primary diseases, or liver function abnormalities, AST, ALT greater than 1.1/2 times the normal value, creatinine greater than the upper limit of normal value; psychiatric patients; tumor patients, expected life < 6 months; Patients with renal insufficiency (creatinine, urea nitrogen more than 1.2 times the normal range) with a history of immunodeficiency, including HIV positive or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation;]
⑤ Allergic to anesthetics and other drugs
⑥ Pregnant or lactating women
⑦ Refused to participate in this clinical researcher for various reasons
⑧ Partners or first-degree relatives of research center staff or researchers
⑨ Other situations in which the researchers considered unsuitable for inclusion

研究实施时间：

Study execute time：

从 From 2023-01-01 00:00:00至 To 2025-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2023-03-17 00:00:00 至 To 2024-12-31 00:00:00

干预措施：

Interventions：

组别：

实验组一

样本量：

 20

Group：

Group1

Sample size：

干预措施：

使用临床安全性检验通过的 AlloDerm SELECT 脱细胞真皮基质

干预措施代码：

Intervention：

Using AlloDerm SELECT acellular dermal matrix

Intervention code：

组别：

实验组二

样本量：

 20

Group：

Group2

Sample size：

干预措施：

使用临床安全性检验通过的 Geistlich Mucograft 胶原基质膜

干预措施代码：

Intervention：

Using Geistlich Mucograft Collagen Matrix Membrane

Intervention code：

组别：

对照组

样本量：

 20

Group：

Control Group

Sample size：

干预措施：

进行自体游离龈瓣移植

干预措施代码：

Intervention：

Using Autogenous free gingival flap transplantation

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 陕西 

市(区县)：

 西安市 

Country：

China

Province：

Shaanxi

City：

Xi'an

单位(医院)：

 空军军医大学口腔医院 

单位级别：

 三甲 

Institution
hospital：

School of Stomatology, Air Force Medical University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

颊侧附着龈宽度

指标类型：

主要指标

Outcome：

Buccal attached gingival width

Type：

Primary indicator

测量时间点：

术后2周、1个月，2个月，3个月及6个月

测量方法：

标尺测量

Measure time point of outcome：

Postoperative 2 weeks, 1 month, 2 months, 3 months and 6 months

Measure method：

Scale measurement

指标中文名：

颊侧附着龈厚度

指标类型：

主要指标

Outcome：

Buccal attached gingival thickness

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

附着龈颜色

指标类型：

次要指标

Outcome：

Attached gum color

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

附着龈水肿情况

指标类型：

次要指标

Outcome：

Attached gingival edema

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

患者痛感

指标类型：

次要指标

Outcome：

Patient's pain

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：

无

组织：

Sample Name：

None

Tissue：

人体标本去向

 其它  

说明

Fate of sample：

0thers  

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 25 岁 years
最大 Max age 50 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）：

本试验采用纸质病例报告表和电子数据收集平台的形式进行数据收集。采用随机数的方法对患者进行随机，当受试者符合入选标准且不满足全部排出标准，并签署知情同意书后，根据入组顺序按照随机数表将患者分配至各个组别。

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

The paper case report form and electronic data collection platform were used for data collection in this experiment. Random number method was used to randomize the patients. When the subjects met the inclusion criteria but did not meet all exclusion criteria and signed the informed consent, the patients wer

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：

本实验是前瞻性、单中心、随机、开放标签、生物材料平行对照临床研究，不涉及盲法。

Blinding：

This study is a prospective, single-center, randomized, open-label, biomaterial parallel controlled clinical study, which does not involve blindness.

是否共享原始数据：

IPD sharing

否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）：

自研究结果发表后可以共享原始数据，请邮件向研究者索要

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

Raw data can be shared after publication. Please email the investigators for a request

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：

纸质版病历记录表保存于空军军医大学口腔医院牙周病科资料室，由专人负责保管。 电子版EDC由专人负责录入整理，后续可以用于数据统计。

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

The paper medical record form was stored in the data room of Department of Periodontology, Hospital of Stomatology, Air Force Medical University by special person. The electronic version of EDC is entered and sorted by a special person, and can be used for data statistics in the future.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2023-03-17 15:50:29