Auditory Restoration and Outcomes After Gene Therapy and Cochlear Implantation: a PRospective Cohort Analysis (AURORA)

This cohort study aims to explore the trends and differences in multidimensional perceptual levels of patients after cochlear implants or gene therapy, as well as to comprehensively assess the efficacy of gene therapy for congenital deafness, thus providing a reference for making a well-rounded postoperative rehabilitation protocol for gene therapy patients.

Study Overview

• Status: Recruiting
• Conditions: Hearing Loss; Genetic Disease; Speech Perception

Detailed Description

Cochlear implant patients exhibit improved speech perception in quiet environments after surgery, but their music perception and speech perception under noise are still unsatisfactory. Gene therapy is a novel and promising treatment for congenital hearing loss to recover natural hearing sensations. To date, for patients with congenital deafness, there has been no study on their ability to perceive and understand sounds, such as speech perception in noise, music and directional perception, after hearing recovery owing to gene therapy. In addition, the difference between the two treatments in those perceptual levels postoperatively remains unknown.

Therefore, the investigators designed a single-center cohort study. Based on the intervention method, congenital deafness patients are divided into two groups: the cochlear implant group and the gene therapy group. In the present study, a full-scale evaluation of the two groups will be conducted. The battery encompasses auditory speech perception, cognition, psychological status, and auditory cortex development. A comparative analysis will be conducted to examine multidimensional differences between the two groups, shedding light on the divergent outcomes of gene therapy and cochlear implants for patients with congenital deafness.

• Study Type: Observational
• Enrollment (Estimated): 180

Contacts and Locations

• Study Contact: Name: Yilai Shu, M.D. & Ph.D.; Phone Number: +86 21 6437 7134; Email: yilai_shu@fudan.edu.cn

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Not yet recruiting
      • Peking Union Medical College Hospital
      • Contact: Guodong Feng; Phone Number: +86 21 5515 9599; Email: fengguodong2013@163.com
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Not yet recruiting
      • The First Affiliated Hospital of Zhengzhou University
      • Contact: Rongqun Zhai; Phone Number: +86 371 6691 3345; Email: rongqunzhai2009@126.com
  • Hunan
    • Changsha, Hunan, China, 410011
      • Not yet recruiting
      • The Second Xiangya Hospital of Central South University
      • Contact: Qin Wang; Phone Number: +86 731 8529 5888; Email: 455616210@qq.com
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Not yet recruiting
      • The First Affiliated Hospital of Nanchang University
      • Contact: Yuanping Xiong; Phone Number: 0791-88692748; Email: yuanping_xiong@163.com
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200031
      • Recruiting
      • Eye & ENT Hospital of Fudan University
      • Contact: Yilai Shu, M.D. & Ph.D.; Phone Number: +86 21 6437 7134; Email: yilai_shu@fudan.edu.cn
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Not yet recruiting
      • West China Hospital, Sichuan University
      • Contact: Yu Zhao; Phone Number: 028-85422114; Email: yuzhao@wchscu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The number of enrollments in the gene therapy group is expected to be 90, and that of the cochlear implant group is expected to be at least 90, according to the pairing ratio of at least 1:1 between the cochlear implant group and gene therapy group. An estimated 30 healthy subjects are expected to be recruited (optional, subject to recruitment feasibility) for electroencephalography and/or functional near-infrared spectroscopy assessments.

Description

Inclusion Criteria:

Patients with congenital hearing loss with hearing thresholds ≥65 dB receive either gene therapy (previously received gene therapy and standardized postoperative rehabilitation and follow-up or plan to receive gene therapy), or cochlear implant surgery. Healthy participants with bilateral hearing thresholds within the normal range (≤20 dB), generally matched to the gene therapy group and the cochlear implant group by age and sex.

Age ≥ 6 months, regardless of gender. Mandarin Chinese as the native language. Participants and their guardians must provide informed consent before the trial, voluntarily sign a written consent form, and commit to follow-up at specified time points.

Capable of effective communication with researchers with the assistance of their guardians and willing to cooperate and comply with the researchers' requirements.

The participant's guardians should have a correct understanding of the trial and appropriate expectations regarding potential benefits.

Exclusion Criteria:

Presence of other otological disorders that may interfere with the surgical outcome or interpretation of study endpoints, such as middle/inner ear dysplasia or malformations revealed by CT/MRI scans performed within the past 3 months that may affect the therapeutic effect, vestibular-cochlear nerve abnormalities, acute/chronic otitis media, Meniere's disease, etc.

Presence of other severe congenital diseases. Presence of severe systemic diseases or diseases in the acute phase, such as pulmonary tuberculosis, active hepatitis B or C infection, active herpes zoster infection, pancreatitis, renal insufficiency, etc.

Individuals with low immunity, a history of immune deficiency or organ transplantation.

Individuals with a history of neurological or mental disorders, such as epilepsy or dementia.

Patients with contraindications to surgery or anesthesia, as assessed by a surgeon, anesthetist, or designated personnel, such as cardiovascular or cerebrovascular events in the past 6 months, allergies to the planned medications, etc.

Gene therapy group: gene therapy did not restore hearing; Cochlear implant group: presence of hereditary syndromic deafness or other conditions that seriously affect the efficacy evaluation.

Any other conditions for which the investigators consider the subject unsuitable for participation in this clinical study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Gene Therapy Group; The study will recruit gene therapy patients who are definitely diagnosed with autosomal recessive deafness 9 (DFNB9).
Cochlear Implant Group; The study will recruit cochlear implant patients with congenital deafness.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Auditory speech perception	Meaningful Auditory Integration Scale (MAIS)/Infant-toddler Meaningful Auditory Integration Scale (IT-MAIS): the MAIS (≥3 years old)/IT-MAIS (0~3 years old) is an auditory perception test with a total score of 40 points. The higher the score the better the hearing ability.	Preoperatively and at 13, 26, and 52 weeks postoperatively, with subsequent assessments every 6 or 12 months up to 5 years after treatment.
Auditory speech perception	Categories of Auditory Performance (CAP): the CAP is an auditory perception test with a total levels of 8. The higher the level the better the hearing ability.	Preoperatively and at 13, 26, and 52 weeks postoperatively, with subsequent assessments every 6 or 12 months up to 5 years after treatment.
Auditory speech perception	Speech Intelligibility Rating (SIR): the SIR is a speech perception test with a total levels of 5. The higher the level the better the hearing ability.	Preoperatively and at 13, 26, and 52 weeks postoperatively, with subsequent assessments every 6 or 12 months up to 5 years after treatment.
Auditory speech perception	Meaningful Use of Speech Scale (MUSS): the MUSS is a speech perception test with a total score of 50 points. The higher the score the better the hearing ability.	Preoperatively and at 13, 26, and 52 weeks postoperatively, with subsequent assessments every 6 or 12 months up to 5 years after treatment.
Auditory speech perception	Speech, Spatial, and Qualities of Hearing Scale for Parents (SSQ-P): the SSQ-P is an auditory speech and sound location perception test with a total score of 10 points. The higher the score the better the auditory speech and sound location ability.	Preoperatively and at 13, 26, and 52 weeks postoperatively, with subsequent assessments every 6 or 12 months up to 5 years after treatment.
Auditory speech perception	Mandarin Speech Perception (MSP): the MSP is a speech test software included the perception tests of monosyllable, disyllable and sentence recognition in quiet and noise environment. The higher the score the better the auditory speech ability.	Preoperatively and at 13, 26, and 52 weeks postoperatively, with subsequent assessments every 6 or 12 months up to 5 years after treatment.
Auditory speech perception	The Angel Test: the Angel Test is a speech test software included the perception tests of environmental sound test, final recognition test, initial recognition test, lexical tone test, music tests, and auditory resolution tests. The higher the score or the lower the thresholds, the better the auditory speech perception.	Preoperatively and at 13, 26, and 52 weeks postoperatively, with subsequent assessments every 6 or 12 months up to 5 years after treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Growth and development assessment	Griffiths development scales(GDS)/Wechsler Intelligence Scale for Children, 4e (WISC-IV): the GDS (0~6 years old)/ WISC-IV (8-16 years old) is a cognitive function test. For children aged 6-8 years, the assessment instrument was selected according to their developmental status and ability to cooperate with the testing procedures.	Preoperatively and at 13, 26, and 52 weeks postoperatively, with subsequent assessments every 6 or 12 months up to 5 years after treatment.
Psychological status	Strengths and Difficulties Questionnaire(SDQ): the SDQ is a psychological status test with a total score of 25 points. The lower the score the better the psychological status.	Preoperatively and at 13, 26, and 52 weeks postoperatively, with subsequent assessments every 6 or 12 months up to 5 years after treatment.
Cortical auditory processing	Electroencephalogram (EEG): the EEG is a non-invasive brain imaging method that uses brain maps to assess changes in auditory and speech-related cortex.	Preoperatively and at 13, 26, and 52 weeks postoperatively, with subsequent assessments every 6 or 12 months up to 5 years after treatment.
Cortical auditory processing	Functional near-infrared spectroscopy (fNIRS): the fNIRS is a non-invasive brain imaging method that uses brain maps to assess changes in auditory and speech-related cortex.	Preoperatively and at 13, 26, and 52 weeks postoperatively, with subsequent assessments every 6 or 12 months up to 5 years after treatment.

Collaborators and Investigators

• Sponsor: Eye & ENT Hospital of Fudan University
• Collaborators: Shanghai Rehabilitation Institute for the Exceptional Children
• Investigators: Study Chair: Yilai Shu, M.D. & Ph.D., Eye & ENT Hospital of Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2024
• Primary Completion (Estimated): October 10, 2029
• Study Completion (Estimated): December 22, 2029

Study Registration Dates

• First Submitted: December 26, 2023
• First Submitted That Met QC Criteria: January 25, 2024
• First Posted (Actual): February 1, 2024

Study Record Updates

• Last Update Posted (Actual): August 31, 2026
• Last Update Submitted That Met QC Criteria: August 26, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Gene Therapy; Cochlear Implant; Speech Perception; Congenital Hearing Loss; DFNB9
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Ear Diseases; Hearing Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Genetic Diseases, Inborn; Hearing Loss
• Other Study ID Numbers: 2023185-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No