Audiovestibular Function in Infratentorial Superficial Siderosis

Study Overview
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Brief Summary
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One in six people in the United Kingdom and over 400 million people worldwide have disabling hearing loss. This figure will double by 2050 as predicted by the World Health Organisation. There is an urgent need to improve our knowledge regarding hearing loss, its underlying mechanisms, optimal diagnostic modalities, reliable and accurate functional and imaging biomarkers. A less-well studied condition associated with progressive hearing loss is infratentorial superficial siderosis (iSS). It results from iron deposition along the surfaces of brain structures which control hearing and balance. It is currently considered uncommon, but may well be under-recognised and therefore under-reported. Despite its severity, our current understanding of its impact on the hearing (auditory) and balance (vestibular) functions is limited, and this has an adverse impact on the treatment offered to these patients. Additionally, iSS patients have been reported to have cognitive impairment yet literature reports of cognitive assessment in iSS are few. The cognitive dysfunction may be specific to iSS or due to progressive hearing impairment or a combination of both, and further studies are required to establish this. Olfaction is also known to be affected in patients with iSS yet is rarely reported in the literature. Due to the significant morbidity and progressive nature, there is a clear need to improve our understanding of the audiovestibular dysfunction resulting from iSS. The aim of this study is to comprehensively assess audiovestibular function in iSS compared to age-related hearing loss and the controls/normative data and as a means to quantify deficits for monitoring disease progression and response to treatment, to assess the impact on the quality of life, to analyse clinically-obtained data (including imaging, cognitive and laboratory data), and correlate these with functional findings in iSS.

Official Title
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Clinical and Imaging Biomarkers of Audiovestibular Function in Infratentorial Superficial Siderosis

Conditions
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Siderosis, Neurological Disorder, Rare Diseases, Age Related Hearing Loss, Presbycusis

Intervention / Treatment
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* Diagnostic Test: Hearing assessment
* Diagnostic Test: Vestibular/balance assessment
* Other: Quality of life assessment
* Diagnostic Test: Olfactory (smell) function testing
* Genetic: DNA bio-banking


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Siderosis group: adults (male and female) of 18+ years old with a known diagnosis of iSS (defined using standardised radiological criteria) confirmed by a consultant neurologist with expertise in this condition at University College London Hospitals National Health Service (NHS) Foundation Trust Age-related hearing loss (ARHL) group: adults (male and female) of 18+ years old with ARHL Control group: adults (male and female) of 18+ years old with no previous diagnosis of hearing loss or no known neurological disorder (including iSS) that affects hearing, with the aim to recruit such participants of 50 years of age and above; however, should difficulty with the recruitment of such participants arise, participants of 18 years of age and above will be invited to participate in the study. Exclusion Criteria: All groups: individuals younger than 18 years old; individuals with a physical or mental impairment that prevents the potential participant from giving informed consent or undergoing the hearing and/or vestibular assessment; Siderosis group: individuals with no prior diagnosis of iSS Age-related hearing loss (ARHL) group: individuals with no previous diagnosis of ARHL or with a diagnosis of hearing loss of aetiology other than age-related; individuals with a history of exposure to high-intensity noise or ototoxic drugs or evidence of middle ear disease/dysfunction or family history of non age-related hearing loss; Control group: individuals with a known history of hearing loss (of any cause) or with a known neurological disorder that affects their hearing; individuals with history of exposure to high-intensity noise or ototoxic drugs or evidence of middle ear disease or family history of non age-related hearing loss;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Siderosis (iSS) group<br>participants with a known diagnosis of infratentorial superficial siderosis (defined using standardised radiological criteria) confirmed by a consultant neurologist with expertise in this condition at University College London Hospitals National Health Service (NHS) Foundation Trust | Diagnostic Test: Hearing assessment<br>* All study participants will undergo hearing tests, including hearing-specific questionnaires<br>Diagnostic Test: Vestibular/balance assessment<br>* Siderosis group participants will undergo vestibular/balance tests, including gait assessment and balance-specific questionnaires<br>Other: Quality of life assessment<br>* All study participants will be asked to complete a set of quality of life questionnaires<br>Diagnostic Test: Olfactory (smell) function testing<br>* Siderosis group participants will undergo a formal smell identification testing by means of self-administered smell chart to identify the revealed scents<br>Genetic: DNA bio-banking<br>* Siderosis group participants will be asked to provide a saliva sample for DNA bio-banking<br>|
| Age-related hearing loss (ARHL) group<br>participants with age-related hearing loss (as identified from participant's clinical history and examination, with hearing thresholds confirmed on a pure-tone audiogram) | Diagnostic Test: Hearing assessment<br>* All study participants will undergo hearing tests, including hearing-specific questionnaires<br>Other: Quality of life assessment<br>* All study participants will be asked to complete a set of quality of life questionnaires<br>|
| Control group<br>participants with no known or previously reported hearing loss (as identified from participant's clinical history and examination, with hearing thresholds confirmed on a pure-tone audiogram) | Diagnostic Test: Hearing assessment<br>* All study participants will undergo hearing tests, including hearing-specific questionnaires<br>Other: Quality of life assessment<br>* All study participants will be asked to complete a set of quality of life questionnaires<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hearing evaluation | An array of audiological (hearing) tests will be performed to comprehensively assess hearing function in siderosis group participants and in age-related hearing loss and control groups. The hearing tests will include psychophysical, physiological and electrophysiological measures. | Inclusion visit | 
| Vestibular/balance evaluation | An array of clinical vestibular and balance tests will be performed to comprehensively assess vestibular/balance function in siderosis group participants, including scale for the assessment and rating of ataxia and functional gait assessment. | Inclusion visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life assessment | Hearing-specific questionnaires and general quality-of-life questionnaires will be provided to all study participants to complete at their initial study visit and at 12-months (siderosis group participants will also be provided with balance-specific questionnaires). | Inclusion visit and at 12 months | 
| Correlation between clinically obtained imaging (siderosis group participants) and the hearing and balance assessment results | Siderosis group participants will undergo formal imaging procedures as part of their clinical care pathway. The results of this clinical assessment will be correlated with the results obtained from hearing and vestibular/balance assessments performed during the study. | Inclusion visit | 
| Correlation between clinically obtained results of cerebrospinal fluid (siderosis group participants) and the hearing and balance assessments | Siderosis group participants will undergo a formal assessment of cerebrospinal fluid as part of their clinical care pathway. The results of this clinical assessment will be correlated with the results obtained from hearing and vestibular/balance assessments performed during the study. | Inclusion visit | 
| Correlation between clinically obtained results of cognitive function assessment (siderosis group participants) and the hearing and balance assessments | Siderosis group participants will undergo a formal neuro-cognitive assessment as part of their clinical care pathway. The results of this clinical assessment will be correlated with the results obtained from hearing and vestibular/balance assessments performed during the study. | Inclusion visit | 
| Smell Identification Test | Smell Identification Test will be administered to siderosis group participants to assess olfactory function. | Inclusion visit | 
| DNA bio-banking | Saliva samples for DNA bio-banking will be obtained from siderosis group participants. | Inclusion visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Superficial siderosis, infratentorial, Nervous system diseases, Hearing loss, Hearing tests, Auditory pathways, Vestibulocochlear nerve, Ataxia, Vestibular function tests, Biomarkers, Central nervous system