DFNA9NCT03707756
Systematic Review of Phenotypical Characteristics of P51S COCH Mutation
An observational study of DFNA9, run by Jessa Hospital.
Trial summary
Gene mutations account for more than 60% of congenital sensorineural hearing loss (SNHL) in Western Countries. Hereditary SNHL does not necessarily start at birth, however, as many causative gene mutations only begin to express at much later ages, such as for example DFNA9, also known as the ninth discovered autosomal… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- DFNA9
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 May 2018to 30 Sep 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- Child, Adult, Older adult
Study population: all affected subjects carrying the P51S COCH mutation
Who may be able to join
- P51S carriership
Who cannot join
- no P51S carriership
About this study
Official title: Systematic Review of Phenotype Characteristics of DFNA9 Caused by the Pro51 Ser (P51S) Mutation in COCH
Gene mutations account for more than 60% of congenital sensorineural hearing loss (SNHL) in Western Countries. Hereditary SNHL does not necessarily start at birth, however, as many causative gene mutations only begin to express at much later ages, such as for example DFNA9, also known as the ninth discovered autosomal dominant SNHL.
It is characterized by a late onset of rapid progressive SNHL together with accompanying vestibular impairment. The first reported DFNA9 patients were carrying the c.151 C>T mutation in COCH, which is the result of a substitution of cytosine by thymine nucleotide of the 151th base pair (c.151C>T). At protein level, this missense point mutation induces a mistranslation to a serine instead of a proline amino-acid (p.Pro51Ser, (P51S)), producing mutant cochlin that cause a dominant negative effect due to misfolding.
Read more
In the perspective of promising future hearing and vestibular treatment developments, such as gene therapy, stem cell therapy, neural regeneration, in association with cochlear and/or vestibular implantation, a more accurate understanding of the onset of the very first signs of the auditory and vestibular deterioration is important. However, in early stages these first signs of impairment are very discrete and pre-symptomatic.
The aim of this systematic review is to identify studies related to DFNA9, caused by the P51S COCH variant, describing detailed genotype-phenotype correlation in relation to the age and to investigate the age of onset of the SNHL and peripheral vestibular function as well as their progression in relation to age.
Read the detailed description
The strategy and methodology used for the systematic review was based on the PRISMA Statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Medline, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, ISI Web of Knowledge and Web of Science were searched. Information was retrieved about COCH mutations causing DFNA9, including phenotype, genotype, audiometric and vestibular data.
Audiometric data were collected using individual measurements or pure tone average incides in the selected records.In case of different audiometric data presentation, for instance audiograms or different pure tone average (PTA) plots against age, a comprehensive assessment and inventory of all individual measurements was conducted. All available measurements at both ears per frequency were inventoried and a binaural mean value for each frequency per age was averaged, before the calculation of the indices. If longitudinal measurements of the same individual were shown, all the available data was included in the assessment.
The following parameters for the audiometric data were inventoried: pure tone average (PTA), Annual Threshold detarioration (ATD) per frequency and/or PTA, Age-related Typical Audiogram (ARTA) and age of onset of the sensorineural hearing loss (SNHL).
For the vestibular function, all different parameters of the vestibular function were inventoried. Normative values, if mentioned, were used to evaluate the measurements. An overall inventory of all individual vestibular measurements in relation to age was conducted.
The following parameters for the vestibular function were inventoried: Time Constant (T) derived from velocity-step test (VST) in seconds, Caloric response gain on electronystagmography, Annual vestibular deterioration rate and age of onset of vestibular dysfunction.
- Conditions
- DFNA9
- Keywords
- DFNA9, COCh, Mutation, Genotype-phenotype
What is being measured
The primary outcome is the main question the study is designed to answer.
age of onset sensorineural hearing loss
Age of onset sensorineural hearing loss (years) in P51S COCH mutation carriers
Measured: 10 years
annual threshold deterioration
Annual threshold deterioration (decibel hearing loss per year) in P51S COCH mutation carriers
Measured: 10 years
age of onset vestibular dysfunction
Age of onset vestibular dysfunction (time constant T (seconds) in P51S COCH mutation carriers
Measured: 10 years
annual vestibular deterioration rate
Annual vestibular deterioration (seconds per year) in P51S COCH mutation carriers
Measured: 10 years
Pure Tone Average (PTA)
Pure tone average (PTA) in decibel hearing loss (dB HL) of P51S COCH mutations carriers
Measured: 10 years
Age-Related Typical Audiogram (ARTA)
Age-related typical audiogram (ARTA) of P51S COCH mutation carriers
Measured: 10 years
Time Constant 'T'
Time constant 'T' with velocity-step test(VST) (seconds) in P51S COCH mutation carriers
Measured: 10 years
gain of caloric test of ENG
summation of gain in caloric test of electronystagmography (ENG) (degrees per second) of P51S COCH mutation carriers
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2018
- Study start1 May 2018
- Primary completion30 Sep 2018
- Study completion30 Sep 2018
Why it stopped: systematic literature review has been completed
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DFNA9Studies 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
- Other
- Time perspective
- Retrospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jessa Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sebastien Janssens de Varebeke, Jessa Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03707756
- Sponsor's protocol ID
- JessaH-ORL-1
- Status last verified
- Oct 2018
- First submitted
- 8 Oct 2018
- Last updated
- 17 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Systematic Review of Phenotype Characteristics of DFNA9 Caused by the Pro51 Ser (P51S) Mutation in COCH
- ClinicalTrials.gov ID
- NCT03707756
- Acronym / sponsor ID
- JessaH-ORL-1
- Conditions
- DFNA9
- Keywords
- DFNA9, COCh, Mutation, Genotype-phenotype
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: systematic literature review has been completed
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Jessa HospitalUniversity, hospital or other
- Study start
- 1 May 2018 (actual)
- Primary completion
- 30 Sep 2018 (actual)
- Study completion
- 30 Sep 2018 (actual)
- First posted
- 16 Oct 2018 (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.
Gene mutations account for more than 60% of congenital sensorineural hearing loss (SNHL) in Western Countries. Hereditary SNHL does not necessarily start at birth, however, as many causative gene mutations only begin to express at much later ages, such as for example DFNA9, also known as the ninth discovered autosomal dominant SNHL.
It is characterized by a late onset of rapid progressive SNHL together with accompanying vestibular impairment. The first reported DFNA9 patients were carrying the c.151 C>T mutation in COCH, which is the result of a substitution of cytosine by thymine nucleotide of the 151th base pair (c.151C>T). At protein level, this missense point mutation induces a mistranslation to a serine instead of a proline amino-acid (p.Pro51Ser, (P51S)), producing mutant cochlin that cause a dominant negative effect due to misfolding.
In the perspective of promising future hearing and vestibular treatment developments, such as gene therapy, stem cell therapy, neural regeneration, in association with cochlear and/or vestibular implantation, a more accurate understanding of the onset of the very first signs of the auditory and vestibular deterioration is important. However, in early stages these first signs of impairment are very discrete and pre-symptomatic.
The aim of this systematic review is to identify studies related to DFNA9, caused by the P51S COCH variant, describing detailed genotype-phenotype correlation in relation to the age and to investigate the age of onset of the SNHL and peripheral vestibular function as well as their progression in relation to age.
Detailed description
The strategy and methodology used for the systematic review was based on the PRISMA Statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Medline, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, ISI Web of Knowledge and Web of Science were searched. Information was retrieved about COCH mutations causing DFNA9, including phenotype, genotype, audiometric and vestibular data.
Audiometric data were collected using individual measurements or pure tone average incides in the selected records.In case of different audiometric data presentation, for instance audiograms or different pure tone average (PTA) plots against age, a comprehensive assessment and inventory of all individual measurements was conducted. All available measurements at both ears per frequency were inventoried and a binaural mean value for each frequency per age was averaged, before the calculation of the indices. If longitudinal measurements of the same individual were shown, all the available data was included in the assessment.
The following parameters for the audiometric data were inventoried: pure tone average (PTA), Annual Threshold detarioration (ATD) per frequency and/or PTA, Age-related Typical Audiogram (ARTA) and age of onset of the sensorineural hearing loss (SNHL).
For the vestibular function, all different parameters of the vestibular function were inventoried. Normative values, if mentioned, were used to evaluate the measurements. An overall inventory of all individual vestibular measurements in relation to age was conducted.
The following parameters for the vestibular function were inventoried: Time Constant (T) derived from velocity-step test (VST) in seconds, Caloric response gain on electronystagmography, Annual vestibular deterioration rate and age of onset of vestibular dysfunction.
Study design
- Observational model
- Other
- Time perspective
- Retrospective
Who may qualify
- Sex
- All
- Age groups
- Child, Adult, Older adult
- Study population
- all affected subjects carrying the P51S COCH mutation
Key inclusion criteria (1 listed)
- P51S carriership
Key exclusion criteria (1 listed)
- no P51S carriership
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
age of onset sensorineural hearing loss
Time frame: 10 years
Age of onset sensorineural hearing loss (years) in P51S COCH mutation carriers
annual threshold deterioration
Time frame: 10 years
Annual threshold deterioration (decibel hearing loss per year) in P51S COCH mutation carriers
age of onset vestibular dysfunction
Time frame: 10 years
Age of onset vestibular dysfunction (time constant T (seconds) in P51S COCH mutation carriers
annual vestibular deterioration rate
Time frame: 10 years
Annual vestibular deterioration (seconds per year) in P51S COCH mutation carriers
Pure Tone Average (PTA)
Time frame: 10 years
Pure tone average (PTA) in decibel hearing loss (dB HL) of P51S COCH mutations carriers
Age-Related Typical Audiogram (ARTA)
Time frame: 10 years
Age-related typical audiogram (ARTA) of P51S COCH mutation carriers
Time Constant 'T'
Time frame: 10 years
Time constant 'T' with velocity-step test(VST) (seconds) in P51S COCH mutation carriers
gain of caloric test of ENG
Time frame: 10 years
summation of gain in caloric test of electronystagmography (ENG) (degrees per second) of P51S COCH mutation carriers
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2018.
Related trials for DFNA9
RecruitingObservational study
Genotype-phenotype Correlation Study of Presymptomatic and Symptomatic DFNA9 Patients
Vestibular Diseases, DFNA9
RecruitingObservational study
Correlation of Radiological Lesions With Vestibular Function in Patients With Bilateral Vestibulopathy
Hearing Loss, Sensorineural, Bilateral Vestibular Deficiency
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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of DFNA9, run by Jessa Hospital.
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 1 inclusion and 1 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: withdrawn, as of the sponsor's last update on 17 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
age of onset sensorineural hearing loss (time frame: 10 years). The study lists 8 primary outcomes in all. 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 17 Oct 2018; AzTrials last refreshed its copy on 8 Nov 2026.