Audiovestibular Function in Infratentorial Superficial Siderosis

NCT ID: NCT04200664

Last Updated: 2025-06-10

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

11 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-02-07

Study Completion Date

2021-10-19

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.

Detailed Description

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This study focuses on a rare condition called infratentorial superficial siderosis (iSS)-a disease where iron gradually accumulates in the superficial layers of the brain and spinal cord. Over time, this buildup can damage the nerves responsible for hearing and balance amongst others, leading to symptoms like progressive hearing loss, dizziness, and problems with coordination. iSS has not been well studied in the past. The hearing and balance function in persons with iSS has been described as variable - meaning, there has not been a specific pattern of hearing loss or imbalance or dizziness that can be associated with iSS. The studies to date have been with small groups of patients but mainly case reports.

The aim of the AVISS study has been to address this gap in the knowledge. This study investigates how iSS affects hearing, balance, and even sense of smell by studying three groups of people:

1. People with iSS, who already have hearing and balance problems.
2. People with age-related hearing loss, to compare how hearing declines over time.
3. People with normal hearing, serving as a control group.

The study will take place over three years, using a range of tests to assess hearing and balance:

* Hearing tests like pure tone audiometry, speech-in-noise assessments, and auditory brainstem response.
* Balance tests such as vestibular evaluations, gait assessments, and head impulse testing.
* Olfactory (smell) tests, since iSS might also affect sensory perception. By collecting this data, the study aims to improve how iSS is diagnosed, identify better rehabilitation methods, and explore new treatment options for those affected.

The study is funded by NIHR UCLH Biomedical Research Centre and the Bernice Bibby Research Trust, ensuring experts have the resources needed to make meaningful discoveries. Ultimately, the goal is to help doctors recognize iSS earlier, support affected individuals more effectively and improve their overall quality of life.

Conditions

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Siderosis Neurological Disorder Rare Diseases Age Related Hearing Loss Presbycusis

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Siderosis (iSS) group

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

Hearing assessment

Intervention Type DIAGNOSTIC_TEST

All study participants will undergo hearing tests, including hearing-specific questionnaires

Vestibular/balance assessment

Intervention Type DIAGNOSTIC_TEST

Siderosis group participants will undergo vestibular/balance tests, including gait assessment and balance-specific questionnaires

Quality of life assessment

Intervention Type OTHER

All study participants will be asked to complete a set of quality of life questionnaires

Olfactory (smell) function testing

Intervention Type DIAGNOSTIC_TEST

Siderosis group participants will undergo a formal smell identification testing by means of self-administered smell chart to identify the revealed scents

DNA bio-banking

Intervention Type GENETIC

Siderosis group participants will be asked to provide a saliva sample for DNA bio-banking

Age-related hearing loss (ARHL) group

participants with age-related hearing loss (as identified from participant's clinical history and examination, with hearing thresholds confirmed on a pure-tone audiogram)

Hearing assessment

Intervention Type DIAGNOSTIC_TEST

All study participants will undergo hearing tests, including hearing-specific questionnaires

Quality of life assessment

Intervention Type OTHER

All study participants will be asked to complete a set of quality of life questionnaires

Control group

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)

Hearing assessment

Intervention Type DIAGNOSTIC_TEST

All study participants will undergo hearing tests, including hearing-specific questionnaires

Quality of life assessment

Intervention Type OTHER

All study participants will be asked to complete a set of quality of life questionnaires

Interventions

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Hearing assessment

All study participants will undergo hearing tests, including hearing-specific questionnaires

Intervention Type DIAGNOSTIC_TEST

Vestibular/balance assessment

Siderosis group participants will undergo vestibular/balance tests, including gait assessment and balance-specific questionnaires

Intervention Type DIAGNOSTIC_TEST

Quality of life assessment

All study participants will be asked to complete a set of quality of life questionnaires

Intervention Type OTHER

Olfactory (smell) function testing

Siderosis group participants will undergo a formal smell identification testing by means of self-administered smell chart to identify the revealed scents

Intervention Type DIAGNOSTIC_TEST

DNA bio-banking

Siderosis group participants will be asked to provide a saliva sample for DNA bio-banking

Intervention Type GENETIC

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;
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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NIHR UCLH Biomedical Research Centre (BRC)

UNKNOWN

Sponsor Role collaborator

Bernice Bibby Research Trust

UNKNOWN

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Doris-Eva Bamiou, Professor

Role: PRINCIPAL_INVESTIGATOR

UCL Ear Institute; UCLH NHS Foundation Trust, UK

David J Werring, Professor

Role: PRINCIPAL_INVESTIGATOR

Stroke Research Centre UCL IoN; UCLH NHS Foundation Trust, UK

Locations

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UCL Ear Institute

London, , United Kingdom

Site Status

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Wilson D, Chatterjee F, Farmer SF, Rudge P, McCarron MO, Cowley P, Werring DJ. Infratentorial superficial siderosis: Classification, diagnostic criteria, and rational investigation pathway. Ann Neurol. 2017 Mar;81(3):333-343. doi: 10.1002/ana.24850. Epub 2017 Jan 28.

Reference Type BACKGROUND
PMID: 28019651 (View on PubMed)

Fearnley JM, Stevens JM, Rudge P. Superficial siderosis of the central nervous system. Brain. 1995 Aug;118 ( Pt 4):1051-66. doi: 10.1093/brain/118.4.1051.

Reference Type BACKGROUND
PMID: 7655881 (View on PubMed)

Koeppen AH, Dickson AC, Chu RC, Thach RE. The pathogenesis of superficial siderosis of the central nervous system. Ann Neurol. 1993 Nov;34(5):646-53. doi: 10.1002/ana.410340505.

Reference Type BACKGROUND
PMID: 8239558 (View on PubMed)

Kumar N. Superficial siderosis: associations and therapeutic implications. Arch Neurol. 2007 Apr;64(4):491-6. doi: 10.1001/archneur.64.4.491.

Reference Type BACKGROUND
PMID: 17420310 (View on PubMed)

IWANOWSKI L, OLSZEWSKI J. The effects of subarachnoid injections of iron-containing substances on the central nervous system. J Neuropathol Exp Neurol. 1960 Jul;19:433-48. doi: 10.1097/00005072-196007000-00010. No abstract available.

Reference Type BACKGROUND
PMID: 14406175 (View on PubMed)

Posti JP, Juvela S, Parkkola R, Roine S. Three cases of superficial siderosis of the central nervous system and review of the literature. Acta Neurochir (Wien). 2011 Oct;153(10):2067-73. doi: 10.1007/s00701-011-1116-0. Epub 2011 Aug 7.

Reference Type BACKGROUND
PMID: 21822983 (View on PubMed)

Sydlowski SA, Cevette MJ, Shallop J. Superficial siderosis of the central nervous system: phenotype and implications for audiology and otology. Otol Neurotol. 2011 Aug;32(6):900-8. doi: 10.1097/MAO.0b013e31822558a9.

Reference Type BACKGROUND
PMID: 21730883 (View on PubMed)

Offenbacher H, Fazekas F, Schmidt R, Kapeller P, Fazekas G. Superficial siderosis of the central nervous system: MRI findings and clinical significance. Neuroradiology. 1996 May;38 Suppl 1:S51-6. doi: 10.1007/BF02278119.

Reference Type BACKGROUND
PMID: 8811680 (View on PubMed)

Sydlowski SA, Levy M, Hanks WD, Clark MD, Ackley RS. Auditory profile in superficial siderosis of the central nervous system: a prospective study. Otol Neurotol. 2013 Jun;34(4):611-9. doi: 10.1097/MAO.0b013e3182908c5a.

Reference Type BACKGROUND
PMID: 23670174 (View on PubMed)

Vibert D, Hausler R, Lovblad KO, Schroth G. Hearing loss and vertigo in superficial siderosis of the central nervous system. Am J Otolaryngol. 2004 Mar-Apr;25(2):142-9. doi: 10.1016/j.amjoto.2003.10.001.

Reference Type BACKGROUND
PMID: 14976664 (View on PubMed)

Takeda T, Kawashima Y, Hirai C, Makabe A, Ito T, Fujikawa T, Yamamoto K, Maruyama A, Tsutsumi T. Vestibular Dysfunction in Patients With Superficial Siderosis of the Central Nervous System. Otol Neurotol. 2018 Jul;39(6):e468-e474. doi: 10.1097/MAO.0000000000001844.

Reference Type BACKGROUND
PMID: 29889788 (View on PubMed)

Pribitkin EA, Rondinella L, Rosenberg Si, Yousem DM. Superficial siderosis of the central nervous system: an underdiagnosed cause of sensorineural hearing loss and ataxia. Am J Otol. 1994 May;15(3):415-8.

Reference Type BACKGROUND
PMID: 8579152 (View on PubMed)

Kwartler JA, De La Cruz A, Lo WW. Superficial siderosis of the central nervous system. Ann Otol Rhinol Laryngol. 1991 Mar;100(3):249-50. doi: 10.1177/000348949110000315. No abstract available.

Reference Type BACKGROUND
PMID: 2006825 (View on PubMed)

van Harskamp NJ, Rudge P, Cipolotti L. Cognitive and social impairments in patients with superficial siderosis. Brain. 2005 May;128(Pt 5):1082-92. doi: 10.1093/brain/awh487. Epub 2005 Mar 23.

Reference Type BACKGROUND
PMID: 15788543 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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https://www.who.int/health-topics/hearing-loss#tab=tab_2

WHO global estimates on prevalence of hearing loss

Other Identifiers

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121603

Identifier Type: -

Identifier Source: org_study_id

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