Audiovestibular Function in Infratentorial Superficial Siderosis

Completed

• Conditions: Neurological Disorder; Presbycusis; Age Related Hearing Loss; Siderosis; Rare Diseases
• Interventions: Diagnostic Test: Hearing assessment; Diagnostic Test: Vestibular/balance assessment; Other: Quality of life assessment; Diagnostic Test: Olfactory (smell) function testing; Genetic: DNA bio-banking

• Registration Number: NCT04200664
• Lead Sponsor: University College, London

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-12-10
• Study First Submitted QC: 2019-12-13
• Study First Posted: 2019-12-16
• Study Start: 2020-02-07
• Primary Completion: 2021-10-19
• Study Completion: 2021-10-19
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-08
• Last Update Posted: 2021-11-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

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;

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Siderosis (iSS) group	Hearing assessment	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
Siderosis (iSS) group	Vestibular/balance assessment	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
Age-related hearing loss (ARHL) group	Hearing assessment	participants with age-related hearing loss (as identified from participant's clinical history and examination, with hearing thresholds confirmed on a pure-tone audiogram)
Age-related hearing loss (ARHL) group	Quality of life assessment	participants with age-related hearing loss (as identified from participant's clinical history and examination, with hearing thresholds confirmed on a pure-tone audiogram)
Control group	Hearing assessment	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)
Siderosis (iSS) group	Quality of life assessment	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
Siderosis (iSS) group	Olfactory (smell) function testing	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
Siderosis (iSS) group	DNA bio-banking	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
Control group	Quality of life assessment	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)

Primary Outcome Measures

Name	Time	Method
Hearing evaluation	Inclusion visit	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.
Vestibular/balance evaluation	Inclusion visit	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".

Secondary Outcome Measures

Name	Time	Method
Quality of life assessment	Inclusion visit and at 12 months	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).
Correlation between clinically obtained imaging (siderosis group participants) and the hearing and balance assessment results	Inclusion visit	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.
Correlation between clinically obtained results of cerebrospinal fluid (siderosis group participants) and the hearing and balance assessments	Inclusion visit	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.
Correlation between clinically obtained results of cognitive function assessment (siderosis group participants) and the hearing and balance assessments	Inclusion visit	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.
Smell Identification Test	Inclusion visit	Smell Identification Test will be administered to siderosis group participants to assess olfactory function.
DNA bio-banking	Inclusion visit	Saliva samples for DNA bio-banking will be obtained from siderosis group participants.

Trial Locations

Locations (2)

University College London Hospitals NHS Foundation Trust; 🇬🇧 London, United Kingdom

UCL Ear Institute; 🇬🇧 London, United Kingdom