Hearing LossNCT04501081
Natural History of Autosomal Dominant Hearing Loss
An observational study of Hearing Loss, run by National Institute on Deafness and Other Communication Disorders (NIDCD) at 1 site in United States.
Trial summary
Background: Hereditary hearing loss is one of the most common sensory disabilities affecting newborns. The main options for people with hereditary hearing loss are hearing aids and cochlear implants. Both options have their limitations and do not restore biological hearing. Read more about this study
- Who is it for?
- Ages 3 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Hearing Loss
- How many people
- 1,100 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Feb 2021to 21 Aug 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 99 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: We will be recruiting individuals with DFNA and their family members. Based on the investigator and clinic's capacity to evaluate an average of 20 subjects and 4 (80) additional family members annually, we project our study may accrue up to 200 probands and 800 family members in the first 10 years and for the duration of the study. Target enrollment is 1000, accrual ceiling is 1100 to allow for screen failures, withdrawals and dropouts)
Who may be able to join
- Affected persons with autosomal dominant hereditary sensorineural hearing loss, preferably confirmed by prior genetic testing
- Affected family members of enrolled participants with known autosomal dominant hereditary hearing loss
- Unaffected Family Members (Healthy Volunteers) of enrolled participant
- Adults must be able to provide informed consent
- Minors must have a parent or guardian able to provide informed consent
- Subjects must be 3-99 years of age
Who cannot join
- Persons with sensorineural hearing loss (SNHL) and/or peripheral vestibular dysfunction associated with a non-genetic etiology such as infection, metabolic or immunologic disorders, or exposure to ototoxic agents such as cisplatin, or aminoglycoside antibiotics will not be included in this protocol.
- Persons with sensorineural hearing loss known to be associated with surgical intervention (e.g. acoustic neuroma removal, failed stapedectomy).
- Prospective study subjects who are cognitively impaired and lack consent capacity, will not be enrolled. The pre-screening eligibility checklist, which will be used and documented for registration under this protocol, is provided in a separate document.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY8664111010, prpl@cc.nih.gov
About this study
Background:
Hereditary hearing loss is one of the most common sensory disabilities affecting newborns. The main options for people with hereditary hearing loss are hearing aids and cochlear implants. Both options have their limitations and do not restore biological hearing. Researchers want to learn if gene editing might be a treatment option.
Read more
Objective:
To understand the genes that cause non-syndromic autosomal dominant hearing loss (DFNA) in people with DFNA as well as their family members.
Eligibility:
People age 3 99 who have DFNA, affected family members of enrolled participants with DFNA, and unaffected family members of enrolled participants
Design:
Participants will be screened with a medical and hearing history. Their medical records will be reviewed.
Participants will have hearing tests. They will wear headphones or earplugs. They will listen to tones, sounds, and words and may be asked to describe what they hear.
Participants will have balance tests. For these, they will wear googles as they watch moving lights or as cold or warm air is blown into their ears. They will sit in a spinning chair in a quiet, dark booth. From a reclined position, they will raise their head while listening to clicking sounds.
Participants will have blood drawn through a needle in the arm. Some blood will be used for gene testing.
Some participants will have 2 skin biopsies. The skin will be washed, and a numbing medicine will be injected. Two small pieces of skin will be removed.
Participants may have a physical exam.
Participation will last for up to 20 years. Participants may give medical updates once a year.
Read the detailed description
Hereditary hearing loss is one of the most common sensory disabilities affecting newborns (approximately 1/1000 live births). Currently, the main treatment options for patients with hereditary hearing loss include hearing aids and cochlear implantation. Both of these treatment options have limitations and are incapable of restoring natural hearing. Over the past few years, several studies have demonstrated the feasibility of using gene therapy to improve hearing in mouse models of human hereditary hearing loss. Nonsyndromic autosomal dominant sensorineural hearing loss (DFNA) is an attractive target for gene therapy since patients with DFNA usually develop hearing loss later during childhood or even adulthood. This allows for a longer time period during which therapeutic intervention can be delivered before the onset of potentially irreversible functional and pathologic changes. The genome editing technology has the potential of correcting the underlying genetic mutations in affected cell types. In this study, we plan to assess the efficacy of genome editing on cultured primary or immortalized fibroblasts obtained from DFNA patients. These patients and their family members will also be followed longitudinally to better characterize the natural history of DFNA. This will provide baseline data for DFNA that will be important for interpreting the results of future clinical trials of inner ear gene therapy.
A summary of the study is listed below:
- Primary objectives Objective: The primary objective of this study will be to determine if mutant alleles of genes causing autosomal dominant hearing loss (DFNA) can be inactivated by genome editing tools. Study population: One proband per DFNA mutation. Study design: Single subject design. Outcome measures: Determine if genome editing could be applied to modify mutations in cultured primary or immortalized fibroblasts from patients with non- syndromic autosomal dominant hearing loss. The main outcome measure are, 1) efficiency of genome editing in DFNA fibroblasts and 2) specificity of genome editing at targeting the mutant allele.
- Secondary objectives
Objective: The secondary objective of the study is to record the natural history of individuals with DFNA as well as their family members. We will identify the clinical, audiologic, and laboratory markers correlated with different genetic causes of DFNA.
Study population: DFNA subjects and family members.
Study design: Prospective longitudinal study.
Outcome measures: Characterize the natural history of non-syndromic autosomal dominant hereditary disorders affecting hearing and/or balance and determining the variability of phenotypes associated with various mutations. The main outcome measures include, 1) severity of hearing loss at baseline (beginning of the study) and 2) progression of hearing loss.
- Conditions
- Hearing Loss
- Keywords
- DFNA, Genome Editing, Natural History
- Medical subject headings
- Hearing Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | DFNA patients and their family members (affected) | |
| 2 | DFNA patients and their family members (unaffected) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine if genome editing could be applied to modify mutations in primary or immortalized cultured fibroblasts from patients with non-syndromic autosomal dominant hearing loss.
After determination of the genetic mutation involved with the hearing loss, gRNAs will be generated which will target the mutation in individual probands. Specific outcome measures that will be collected include, 1) testing the efficiency of individual gRNAs at inducing genome editing in primary or immortalized fibroblast cultures from DFNA patients, and 2) assessing the specificity of individual gRNAs at inducing genome editing in both the mutant10. The efficiency of individual gRNAs at inducing genome editing will be assessed by the presence of indels in the mutant allele using deep sequencing. The specificity of genome editing for each gRNA will be assessed by comparing the genome editing efficiency of each gRNA at targeting the mutant allele vs. the wild type allele.
Measured: Ongoing
Secondary outcomes (2)
severity of hearing loss at baseline (beginning of the study)
The baseline variables (demographic and clinical characteristics) are:-age of onset of hearing loss-sex-family history of hearing loss-history of noise exposure-history of head trauma-laterality of hearing loss
Measured: ongoing
progression of hearing loss.
-presence of vestibular dysfunction as measured by vestibular testing (VNG, VEMP, rotary chair)-presence of inner ear malformation as assessed by temporal bone CT and or MRI of brain and IAC if deemed clinically necessary
Measured: ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2020
- Study start9 Feb 2021
- Primary completion21 Aug 2029 (estimated)
- Study completion21 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hearing LossStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Family based
- Time perspective
- Prospective
- Enrolment
- 1,100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute on Deafness and Other Communication Disorders (NIDCD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Joshua M Levy, M.D., Principal investigator, National Institute on Deafness and Other Communication Disorders (NIDCD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04501081
- Sponsor's protocol ID
- 200047
- Other IDs
- 20-DC-0047
- Status last verified
- 3 Nov 2026
- First submitted
- 5 Aug 2020
- Last updated
- 6 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History of Autosomal Dominant Hearing Loss
- ClinicalTrials.gov ID
- NCT04501081
- Acronym / sponsor ID
- 200047
- Conditions
- Hearing Loss
- Keywords
- DFNA, Genome Editing, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,100 participants (estimated)
- Lead sponsor
- National Institute on Deafness and Other Communication Disorders (NIDCD)US National Institutes of Health
- Study start
- 9 Feb 2021 (actual)
- Primary completion
- 21 Aug 2029 (estimated)
- Study completion
- 21 Aug 2029 (estimated)
- First posted
- 6 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Hereditary hearing loss is one of the most common sensory disabilities affecting newborns. The main options for people with hereditary hearing loss are hearing aids and cochlear implants. Both options have their limitations and do not restore biological hearing. Researchers want to learn if gene editing might be a treatment option.
Objective:
To understand the genes that cause non-syndromic autosomal dominant hearing loss (DFNA) in people with DFNA as well as their family members.
Eligibility:
People age 3 99 who have DFNA, affected family members of enrolled participants with DFNA, and unaffected family members of enrolled participants
Design:
Participants will be screened with a medical and hearing history. Their medical records will be reviewed.
Participants will have hearing tests. They will wear headphones or earplugs. They will listen to tones, sounds, and words and may be asked to describe what they hear.
Participants will have balance tests. For these, they will wear googles as they watch moving lights or as cold or warm air is blown into their ears. They will sit in a spinning chair in a quiet, dark booth. From a reclined position, they will raise their head while listening to clicking sounds.
Participants will have blood drawn through a needle in the arm. Some blood will be used for gene testing.
Some participants will have 2 skin biopsies. The skin will be washed, and a numbing medicine will be injected. Two small pieces of skin will be removed.
Participants may have a physical exam.
Participation will last for up to 20 years. Participants may give medical updates once a year.
Detailed description
Hereditary hearing loss is one of the most common sensory disabilities affecting newborns (approximately 1/1000 live births). Currently, the main treatment options for patients with hereditary hearing loss include hearing aids and cochlear implantation. Both of these treatment options have limitations and are incapable of restoring natural hearing. Over the past few years, several studies have demonstrated the feasibility of using gene therapy to improve hearing in mouse models of human hereditary hearing loss. Nonsyndromic autosomal dominant sensorineural hearing loss (DFNA) is an attractive target for gene therapy since patients with DFNA usually develop hearing loss later during childhood or even adulthood. This allows for a longer time period during which therapeutic intervention can be delivered before the onset of potentially irreversible functional and pathologic changes. The genome editing technology has the potential of correcting the underlying genetic mutations in affected cell types. In this study, we plan to assess the efficacy of genome editing on cultured primary or immortalized fibroblasts obtained from DFNA patients. These patients and their family members will also be followed longitudinally to better characterize the natural history of DFNA. This will provide baseline data for DFNA that will be important for interpreting the results of future clinical trials of inner ear gene therapy.
A summary of the study is listed below:
- Primary objectives Objective: The primary objective of this study will be to determine if mutant alleles of genes causing autosomal dominant hearing loss (DFNA) can be inactivated by genome editing tools. Study population: One proband per DFNA mutation. Study design: Single subject design. Outcome measures: Determine if genome editing could be applied to modify mutations in cultured primary or immortalized fibroblasts from patients with non- syndromic autosomal dominant hearing loss. The main outcome measure are, 1) efficiency of genome editing in DFNA fibroblasts and 2) specificity of genome editing at targeting the mutant allele.
- Secondary objectives
Objective: The secondary objective of the study is to record the natural history of individuals with DFNA as well as their family members. We will identify the clinical, audiologic, and laboratory markers correlated with different genetic causes of DFNA.
Study population: DFNA subjects and family members.
Study design: Prospective longitudinal study.
Outcome measures: Characterize the natural history of non-syndromic autosomal dominant hereditary disorders affecting hearing and/or balance and determining the variability of phenotypes associated with various mutations. The main outcome measures include, 1) severity of hearing loss at baseline (beginning of the study) and 2) progression of hearing loss.
Study design
- Observational model
- Family based
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –DFNA patients and their family members (affected) |
| 2 | – | –DFNA patients and their family members (unaffected) |
Who may qualify
- Ages
- 3 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- We will be recruiting individuals with DFNA and their family members. Based on the investigator and clinic's capacity to evaluate an average of 20 subjects and 4 (80) additional family members annually, we project our study may accrue up to 200 probands and 800 family members in the first 10 years and for the duration of the study. Target enrollment is 1000, accrual ceiling is 1100 to allow for screen failures, withdrawals and dropouts)
Key inclusion criteria (6 listed)
- Affected persons with autosomal dominant hereditary sensorineural hearing loss, preferably confirmed by prior genetic testing
- Affected family members of enrolled participants with known autosomal dominant hereditary hearing loss
- Unaffected Family Members (Healthy Volunteers) of enrolled participant
- Adults must be able to provide informed consent
- Minors must have a parent or guardian able to provide informed consent
Key exclusion criteria (3 listed)
- Persons with sensorineural hearing loss (SNHL) and/or peripheral vestibular dysfunction associated with a non-genetic etiology such as infection, metabolic or immunologic disorders, or exposure to ototoxic agents such as cisplatin, or aminoglycoside antibiotics will not be included in this protocol.
- Persons with sensorineural hearing loss known to be associated with surgical intervention (e.g. acoustic neuroma removal, failed stapedectomy).
- Prospective study subjects who are cognitively impaired and lack consent capacity, will not be enrolled. The pre-screening eligibility checklist, which will be used and documented for registration under this protocol, is provided in a separate document.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Determine if genome editing could be applied to modify mutations in primary or immortalized cultured fibroblasts from patients with non-syndromic autosomal dominant hearing loss.
Time frame: Ongoing
After determination of the genetic mutation involved with the hearing loss, gRNAs will be generated which will target the mutation in individual probands. Specific outcome measures that will be collected include, 1) testing the efficiency of individual gRNAs at inducing genome editing in primary or immortalized fibroblast cultures from DFNA patients, and 2) assessing the specificity of individual gRNAs at inducing genome editing in both the mutant10. The efficiency of individual gRNAs at inducing genome editing will be assessed by the presence of indels in the mutant allele using deep sequencing. The specificity of genome editing for each gRNA will be assessed by comparing the genome editing efficiency of each gRNA at targeting the mutant allele vs. the wild type allele.
2 secondary outcomes
severity of hearing loss at baseline (beginning of the study)
Time frame: ongoing
progression of hearing loss.
Time frame: ongoing
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Related trials for Hearing Loss
RecruitingObservational study
Impact of Vestibular Function on Deaf Infants' Activities of Daily Living
Vestibular Dysfunction, Hearing Loss
Recruiting
HEARS-NPS: Addressing Hearing Loss as a Common Unmet Contributor of Neuropsychiatric Symptoms
Alzheimer Disease, Dementia
Not yet recruiting
Hearing Intervention Effects on Brain and Language Development in Children With Bilateral Mild Hearing Loss
Hearing Loss, Bilateral
RecruitingObservational study
Retrospective Analysis of Speech Performance Using the HiRes Ultra and HiRes Ultra 3D Cochlear Implant
Cochlear Hearing Loss
RecruitingObservational study
Audiological Rehabilitation of Children With Unilateral Hearing Loss
Unilateral Hearing Loss
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Joshua M Levy, M.D. principal investigator
National Institute on Deafness and Other Communication Disorders (NIDCD)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hearing Loss, run by National Institute on Deafness and Other Communication Disorders (NIDCD) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Maame S Akumatey ((227) 233-0452, maame.akumatey@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine if genome editing could be applied to modify mutations in primary or immortalized cultured fibroblasts from patients with non-syndromic autosomal dominant hearing loss. (time frame: Ongoing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.