Natural History of Autosomal Dominant Hearing Loss
ConditionHearing Loss
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age3-99
SponsorNational Institute on Deafness and Other Communication Disorders (NIDCD)
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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
Disqualifiers
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).
Trial 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)
Trial design
Design model
Family-based
Time perspective
Prospective
Treatments tested in this trial
Not listed
Trial groups
1,100 Participants
are grouped into 2 trial groupsGroup A: 1
Group B: 2
Trial outcomes
Primary outcomes
1
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.
Time frame
OngoingSecondary outcomes
1
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
Time frame
ongoing2
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
Time frame
ongoingSponsors and contacts
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Source ClinicalTrials.gov