Condition category
Genetic Diseases
Date applied
27/05/2020
Date assigned
16/06/2020
Last edited
11/06/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
According to the data of the national survey in 2006, there are about 27.8 million hearing and speech-disabled people in China, and about 700,000-800,000 hearing-impaired children under 7 years old. One in every 500 newborns has bilateral permanent deafness. Before the age of 5, the incidence of deafness increases to 2.7%, and to 3.5% in adolescence. Research shows that more than 60% of pre-lingual deafness is caused by genetic factors, and the rest is caused by environment or other unknown genetic factors.
As the first genetic hearing loss molecular diagnosis center in China, the genetic deafness molecular diagnosis center of PLA General Hospital has been established for 15 years. A series of achievements have been made in the research of the causes of deafness, discovery of new genes, the molecular epidemiology of deafness in the Chinese population, clinical gene diagnosis and prenatal diagnosis.
The emergence of next-generation sequencing has achieved high throughput and low cost, which brings a broad prospect for the field of gene diagnosis. At present, many gene testing institutions in China have carried out deafness gene testing services, mainly for the most common 3-4 hotspot mutation chips of deafness gene in Chinese population, and 129-167 deafness gene sequencing services. According to the research results of the researchers' center, four common gene mutations can explain about 40% of the causes of deafness, while the detection rate can rise to about 50% - 55% when the detection range is extended to more than 129 deafness genes by high-throughput sequencing technology. Although the improvement of diagnosis rate makes more deaf families or high-risk families obtain genetic consultation and prevention guidance, the promotion and implementation of deafness gene diagnosis and prenatal diagnosis in China still face a series of problems. The testing quality level of testing institutions is uneven, with a lack of standards. The testing report has not yet formed a standard, and the interpretation of variants is not clear. Testing institutions and clinical doctors give inaccurate genetic consultations. There is a lack of a referral and consultation system and process for difficult cases, and a lack of a biological database for deafness in China. The above deficiencies have greatly affected the summary of deafness molecular big data, the guidance of deafness family reproduction and the accurate treatment evaluation of deaf patients. Therefore, the PLA general hospital takes the lead in launching the clinical multicenter research project of deafness gene diagnosis, cooperating with domestic deafness gene testing institutions such as the medical institutions of major provinces and autonomous regions, MyGenostics Inc.; GrandOmics Inc.; WuXi NextCODE Inc.; Capital Genomics Inc. This multicenter study aims to draw a gene map of Chinese people by collecting 10,000 genetic samples; develop clinical consensus/guidelines for the diagnosis of genetic deafness; standardize deafness gene test, report interpretation and genetic consultation; and upgrade the deafness gene test panel.

Who can participate?
Patients with congenital hearing loss or late-onset hearing loss and their families, or patients with acquired sensorineural hearing loss and their families, and hearing normal individuals with a family history of deafness.

What does the study involve?
Patients will take hearing tests, a CT scan and, if necessary, a general examination (thyroid ultrasound, kidney ultrasound, electrocardiogram, chest, abdomen, limbs X-ray, cranial MRI, etc). The researchers collect patients' and their family's medical record information, and collect their blood samples. The genetic testing institution completes the gene test and preliminary data analysis, and the original data will be sent to the designated cloud platform of multicenter for verification and further analysis. The test report will be issued by the testing institution, and approved by the PLA General Hospital and/or qualified sub-centre experts. The PLA General Hospital and the clinical experts of the sending unit will jointly provide patients with genetic consultation. For the cases with suspected pathogenic mutations, the testing institution will provide follow-up research programs. For the cases with no or suspected pathogenic mutation, the leading units of multiple centers will analyze the data again, and discuss the follow-up research plan through regular case discussion and academic activities.

What are the possible benefits and risks of participating?
Taking part in this study can help patients to reduce the risk of deafness in their offspring. It should be noted that this study can not completely exclude the risk of deafness in the next generation, such as pregnancy infection, other environmental factors or rare unknown deafness caused by genetic defects. If the report result is negative, senior experts will re-analyze the report, except for false negatives. If it is positive, it will be verified free of charge, except for false positives. Difficult and complex cases will be provided with priority referral and consultation channels.

Where is the study run from?
Genetic Deafness Molecular Diagnosis Center, PLA General Hospital, Beijing, China

When is the study starting and how long is it expected to run for?
September 2018 to August 2022

Who is funding the study?
Investigator initiated and funded

Who is the main contact?
Prof. Pu Dai
daipu301@vip.sina.com
Prof. Yongyi Yuan
yyymzh@163.com

Trial website

Nil known

Contact information

Type

Scientific

Primary contact

Prof Pu Dai

ORCID ID

Contact details

Fuxing Road 28
Beijing
100853
China
+86 (0)13910213511
daipu301@vip.sina.com

Type

Scientific

Additional contact

Prof Yongyi Yuan

ORCID ID

Contact details

Fuxing Road 28
Beijing
100853
China
+86 (0)13811502776
yyymzh@163.com

Type

Scientific

Additional contact

Dr Bo Gao

ORCID ID

Contact details

Fuxing Road 28
Beijing
100853
China
+86 (0)18515902036
imjd@163.com

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

ChiCTR1800018223

Study information

Scientific title

Clinical demonstration for three-level prevention intervention of birth defect on monogenic disease (deafness)

Acronym

Study hypothesis

The main purpose of this multicenter study is to draw a gene map of Chinese people by collecting 10,000 genetic deafness samples and develop clinical consensus/guidelines for the diagnosis of genetic deafness.

Ethics approval

Approved 26/7/2018, ethical review board of PLA General Hospital (Fuxing Road 28, Beijing, China; +86 (0)10 66937166; 301irb@sina.com), ref: S2018-088-01

Study design

Multicenter observational epidemiological study

Primary study design

Observational

Secondary study design

Epidemiological study

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Genetic deafness

Intervention

The patients and their families will provide blood samples. Next-generation sequencing and Sanger sequencing will be carried out on the samples. The testing institution will analyze preliminary data. The PLA General Hospital and the clinical experts of the sending unit will jointly provide patients with genetic consultation. For the cases with suspected pathogenic mutations, the testing institution will provide follow-up research programs. For the cases with no or suspected pathogenic mutation, the leading units of multiple centers will analyze the data again, and discuss the follow-up research plan.

Intervention type

Other

Phase

Drug names

Primary outcome measure

1. Number of cases in the database of genetic deafness patients in China at 5 years
2. Gene map of genetic deafness patients in China measured using the coverage of pathogenic variant on genetic deafness in the public database at 5 years

Secondary outcome measures

1. Genetic deafness panel measured using coverage and accuracy of pathogenic variant on genetic deafness in the public database at 5 years
2. Guidelines of screening and diagnosis for genetic deafness patients in China measured using the published journal articles at 5 years

Overall trial start date

09/01/2018

Overall trial end date

31/08/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Congenital hearing loss or late-onset hearing loss and their families
2. Patients with congenital malformation of auditory organ and their families
3. Acquired sensorineural hearing loss patients and their families
4. Hearing normal individuals with a family history of deafness

Participant type

Mixed

Age group

All

Gender

Both

Target number of participants

10000

Participant exclusion criteria

1. The patients and their families who refused to participate in the program after receiving the education by doctors
2. The patients with deafness caused by non-genetic factors were definitely diagnosed

Recruitment start date

09/01/2018

Recruitment end date

31/08/2022

Locations

Countries of recruitment

China

Trial participating centre

Chinese PLA General Hospital
Fuxing Road 28, Haidian District
Beijing
100853
China

Trial participating centre

China Rehabilitation Research Center for Hearing and Speech Impairment
A 8 Huixinli, Chaoyang District
Beijing
100029
China

Trial participating centre

The General Hospital of the PLA Rocket Force
16 xinjiekouwei st, Xicheng District, Beijing
Beijing
100088
China

Trial participating centre

Beijing Children’s Hospital of Capital Medical University
56 Nanlishi Road, Xicheng District
Beijing
100045
China

Trial participating centre

China-Japan Friendship Hospital
Yinghuayuan East st, Chaoyang District
Beijing
100029
China

Trial participating centre

Beijing Tongren Hospital of Capital Medical University
1 Dongjiaomin Lane, Dongcheng District
Beijing
100730
China

Trial participating centre

Peking University First Hospital
8 Xishiku St, Xicheng District
Beijing
100034
China

Trial participating centre

Bo GaoPeking University Third Hospital
49 Huayuan North Road, Haidian District
Beijing
100191
China

Trial participating centre

Peking Union Medical College Hospital
41 Damucang Hutong, Xicheng District
Beijing
100032
China

Trial participating centre

Beijing Friendship Hospital of Capital Medical University
95 Yong'an Road, Xicheng District
Beijing
100050
China

Trial participating centre

Shanghai Ninth People's Hospital
No. 639, Manufacturing Bureau Road, Huangpu District
Shanghai
200011
China

Trial participating centre

Fujian Medical University ShengLi Clinical College, Fujian Provincial Hospital
134 East Street
Fuzhou
350001
China

Trial participating centre

Union Hospital Tongji Medical College Huazhong University of Science and Technology
1277 Jiefang Avenue
Wuhan
430022
China

Trial participating centre

The First Affiliated Hospital of UTSC,Anhui Provincial Hospital
17 Lujiang Road
Hefei
230001
China

Trial participating centre

XiangYa Hospital CentralSouth University
87 Xiangya Road
Changsha
410008
China

Trial participating centre

Nanfang Hospital
1838 North Guangzhou Avenue
Guangzhou
510515
China

Trial participating centre

Maternal and Child Heath Care Hospital of Guangdong Province
521 Xingnan Avenue, Panyu District
Guangzhou
511400
China

Trial participating centre

Tianjin First Central Hospital
24 Fukang Road, Nankai District
Tianjin
300192
China

Trial participating centre

Precision medicine research center of Zhengzhou University / precision medicine application center of the Second Affiliated Hospital of Zhengzhou University
No. 40, Daxue Road, Erqi District
Zhengzhou
450000
China

Trial participating centre

Henan Provincial People's Hospital, Department of Otolaryngology Head and Neck
No.7, Weiwu Road
Zhengzhou
450003
China

Trial participating centre

Hebei Medical University Second Hospital
215 Heping West Road
Shijiazhuang
050000
China

Trial participating centre

Maternal and Child Heath Care Hospital of Tangshan
1 Hetai Road, Lunan District
Tangshan
63017
China

Trial participating centre

Children's Hospital of Hebei Province
133 Jianhua South Street, Yuhua District
Shijiazhuang
050030
China

Trial participating centre

Shandong ENT Hospital Affiliated to Shandong University
4 Duanxing West Road, Huaiyin District
Jinan
250022
China

Trial participating centre

Jinan Maternal and Child Care Hospital
No.2, Jianguo Xiaojing 3rd road
Jinan
250000
China

Trial participating centre

Children's Hospital of Nanjing Medical University
72 Guangzhou road, Gulou District
Nanjing
210000
China

Trial participating centre

Zhenjiang Maternal and Child Care Hospital
20 Zhengdong Road
Zhenjiang
212001
China

Trial participating centre

The Affiliated Hospital of Guizhou Medical University
28 Guiyi street
Guiyang
550004
China

Trial participating centre

First Affiliated Hospital of Kunming Medical University
295 Xichang Road
Kunming
650032
China

Trial participating centre

Lanzhou University Second Hospital
No. 82, cuiyingmen, Chengguan District
Lanzhou
730030
China

Trial participating centre

First Affiliated Hospital of Air Force Military Medical University
169 Changle West Road
Xian
710032
China

Trial participating centre

First Affiliated Hospital of Anhui Medical University
218 Jixi Road
Hefei
230000
China

Trial participating centre

Hefei BOE Hospital
Intersection of Dongfang Avenue and Wenzhong Road, Xinzhan District
Hefei
230013
China

Trial participating centre

Second Affiliated Hospital of Anhui Medical University
No. 678, Furong Road, Hefei Economic and Technological Development Zone
Hefei
230601
China

Trial participating centre

Jilin University Second Hospital
218 Ziqiang street, Nanguan District
Changchun
130041
China

Trial participating centre

The Fourth Affiliated Hospital of China Medical University
4 Chongshan East Road, Huanggu District
Shenyang
110032
China

Trial participating centre

Yanbian University Hospital
Juzi Street 1327
Yanji
100191
China

Trial participating centre

Shenyang Women's and Children's Hospital
No. 87, Danan street, Shenhe District
Shenyang
110011
China

Trial participating centre

The First Affiliated Hospital of China Medical University
No. 155, Nanjing North Street, Heping District
Shenyang
110001
China

Trial participating centre

The Children's Hospital, Zhejiang University School of Medicine
57 Zhugan lane
Hangzhou
310003
China

Trial participating centre

Maternal and Child Health Hospital of Liuzhou
66 Sanzhong Road
Liuzhou City
545001
China

Trial participating centre

The People‘s’ Hospital of Guangxi Zhuang Autonomous Region,Department of Otolaryngology Head and Neck
6 Taoyuan Road
Nanning City
530000
China

Trial participating centre

Second Hospital of Shanxi Medical University
No. 382, Wuyi Road
Taiyuan City
030001
China

Trial participating centre

Xinjiang Viger Municipal People's Hospital
No.91, Tianchi Road, Tianshan District
Urumqi City
830001
China

Trial participating centre

Qinghai Provincial People's Hospital
2 Gonghe Road, Chengdong District
Xining
810007
China

Trial participating centre

General Hospital of Ningxia Medical University
804 Shengli South Street, Xingqing District
Yinchuan
750004
China

Trial participating centre

The Affiliated Hospital of Inner Mongolia Medical University
No.1, North Tongdao Road
Hohhot
010000
China

Trial participating centre

The First Affiliated Hospital of Nanchang University
17 Yongwaizheng Street
Nanchang
330006
China

Trial participating centre

The First Hospital Affiliated to AMU(Southwest Hospital)
30 Yanzheng Street, Gaotan, Shapingba District
Chongqing
630038
China

Trial participating centre

Guangdong Second Provincial General Hospital
466 Xingang Middle Road, Haizhu District
Guangzhou
510317
China

Trial participating centre

Shenzhen Longgang Otolaryngology Hospital
No. 3004, Longgang Section, Longgang Avenue, Longgang District
Shenzhen
518001
China

Trial participating centre

Ningbo Women and Children's Hospital, Department of Otolaryngology Head and Neck
266 cishui West Street, Cicheng new town, Jiangbei District
Ningbo
315031
China

Trial participating centre

Shaoxing Women and Children's Hospital, Department of Children Healthcare
305 East Street
Shaoxing
312000
China

Trial participating centre

Ningbo First Hospital, Molecular diagnostic center
59 Liuting Street
Ningbo
315010
China

Trial participating centre

Women's Hospital School of Medicine Zhejiang University
No.1 Bachelor Road
Hanzhou
310006
China

Trial participating centre

Zhejiang Provincial Hospital of TCM, Department of Otolaryngology Head and Neck
54 Youdian Road, Shangcheng District
Hanzhou
310006
China

Trial participating centre

Henan Children's Hospital
No. 255, Gangdu Street
Zhengzhou
450007
China

Trial participating centre

Qingdao Women and Children's Hospital
6 Tongfu Road, Shibei District
Qingdao
266034
China

Trial participating centre

Ningxia Rehabilitation Center for the Disabled
115 Hupan Road, Jinfeng District
YInchuan
750002
China

Trial participating centre

Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
No. 58, Zhongshan 2nd Road
Guangzhou
510080
China

Trial participating centre

Gansu maternity and child-care hospital
143 Qilihe North Street
Lanzhou
730050
China

Trial participating centre

Haidian Maternal and Child Health Hospital
33 Haidian South Road, Haidian District
Beijing
100080
China

Trial participating centre

Shenyang No.4 People's Hospital
20 Huanghe South St, Huanggu District
Shenyang
110031
China

Trial participating centre

Henan Institute of Reproductive Health Science And Technology
26 Jingwu Road, Jinshui District
Zhengzhou
450014
China

Trial participating centre

The First Affiliated Hospital of Hainan Medical University
31 Longhua Road
Haikou
570102
China

Trial participating centre

The Second Hospital of Shandong University
247 Beiyuan Street
Jinan
250033
China

Trial participating centre

The First Affiliated Hospital of Soochow University
No. 899, Pinghai Road
Suzhou
215006
China

Trial participating centre

The Affiliated Children‘s Hospital of Soochow University
No.92 Zhongnan street, Suzhou Industrial Park
Suzhou
215021
China

Trial participating centre

Xuanwu Hospital Capital Medical University
45 Changchun Street, Xicheng District
Beijing
100053
China

Trial participating centre

Baoding Children‘s Hospital
103 Baihua East Road
Baoding
071051
China

Trial participating centre

Qilu Hospital of Shandong University
107 Wenhua West Road
Qingdao
250012
China

Trial participating centre

The Affiliated Hospital of Qingdao University
16 Jiangsu Road, Shinan District
Qingdao
266000
China

Trial participating centre

980 Hospital of the joint service support force of the Chinese People's Liberation Army
398 Zhongshan West Road, Qiaoxi District
Shijiazhuang
050082
China

Sponsor information

Organisation

Chinese PLA General Hospital

Sponsor details

Fuxing Road 28
Beijing
100853
China
+86 (0)10-66938119
daipu301@vip.sina.com

Sponsor type

Hospital/treatment centre

Website

http://www.plagh.cn

Funders

Funder type

Other

Funder name

National key research and development project (2016YFC1000700)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

1. Peer-reviewed scientific journals
2. Conference presentation
3. Publication on website

IPD sharing statement
The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Pu Dai (daipu301@vip.sina.com), Prof. Yongyi Yuan (yyymzh@163.com) and Dr Bo Gao (imjd@163.com). The next-generation sequencing data for genetic deafness can be shared with groups who would like to participate in the trial during the research, and all data will be submitted to the public database (e.g ClinVar) in 3 years after the the end of the trial.

Intention to publish date

01/09/2023

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

10/06/2020: Trial's existence confirmed by Chinese PLA General Hospital Ethics Committee.