Audiovestibular Function in Infratentorial Superficial Siderosis

NCT04200664 | Completed Results

• 1 other identifier: 121603
• Study Type: observational
• Target: 11
• Locations: 1 country
• Sites: 2

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.

Conditions

Siderosis; Neurological Disorder; Rare Diseases; Age Related Hearing Loss; Presbycusis

Keywords

Superficial siderosis, infratentorial; Nervous system diseases; Hearing loss; Hearing tests; Auditory pathways; Vestibulocochlear nerve; Ataxia; Vestibular function tests; Biomarkers; Central nervous system

Outcome Measures

Primary Outcomes (6)

• Hearing Evaluation - Pure Tone Audiometry

  Clinical audiological (hearing) tests were performed to assess hearing function. The hearing tests included psychophysical, physiological and electrophysiological measures, (pure-tone audiometry, tympanometry, auditory brainstem responses and acoustic reflexes). The tests were perfomed in line with the procedure guidelines by the British Society of Audiology (www.thebsa.org.uk). The mean value of pure-tone audiometric thresholds for both ears measured in decibel hearing level (as described in the guidelines by the British Society of Audiology) was calculated and reported. Other parameters were reported as normal or abnormal (in at least one ear) or inconclusive.

  Baseline visit

• Vestibular/Balance Evaluation

  Clinical vestibular and balance tests were performed to assess vestibular/balance function.

  Baseline visit

• Hearing Evaluation - Auditory Brainstem Responses/Acoustic Reflexes

  Clinical audiological (hearing) tests were performed to assess hearing function. The hearing tests included psychophysical, physiological and electrophysiological measures, (pure-tone audiometry, tympanometry, auditory brainstem responses and acoustic reflexes). The tests were perfomed in line with the procedure guidelines by the British Society of Audiology (www.thebsa.org.uk). The mean value of pure-tone audiometric thresholds for both ears measured in decibel hearing level (as described in the guidelines by the British Society of Audiology) was calculated and reported. Other parameters were reported as normal or abnormal (in at least one ear) or inconclusive.

  Baseline visit

• Hearing Evaluation - Tympanogram

  Clinical audiological (hearing) tests were performed to assess hearing function. The hearing tests included psychophysical, physiological and electrophysiological measures, (pure-tone audiometry, tympanometry, auditory brainstem responses and acoustic reflexes). The tests were perfomed in line with the procedure guidelines by the British Society of Audiology (www.thebsa.org.uk). The mean value of pure-tone audiometric thresholds for both ears measured in decibel hearing level (as described in the guidelines by the British Society of Audiology) was calculated and reported. Other parameters were reported as normal or abnormal (in at least one ear) or inconclusive.

  Baseline

• Hearing Evaluation - Otoacoustic Emissions

  Clinical audiological (hearing) tests were performed to assess hearing function. The hearing tests included psychophysical, physiological and electrophysiological measures, (pure-tone audiometry, tympanometry, auditory brainstem responses and acoustic reflexes). The tests were perfomed in line with the procedure guidelines by the British Society of Audiology (www.thebsa.org.uk). The mean value of pure-tone audiometric thresholds for both ears measured in decibel hearing level (as described in the guidelines by the British Society of Audiology) was calculated and reported. Other parameters were reported as normal or abnormal (in at least one ear) or inconclusive.

  Baseline

• Hearing Evaluation - Listening in Spatialised Sentences Noise Test

  Clinical audiological (hearing) tests were performed to assess hearing function. The hearing tests included psychophysical, physiological and electrophysiological measures, (pure-tone audiometry, tympanometry, auditory brainstem responses and acoustic reflexes). The tests were perfomed in line with the procedure guidelines by the British Society of Audiology (www.thebsa.org.uk). The mean value of pure-tone audiometric thresholds for both ears measured in decibel hearing level (as described in the guidelines by the British Society of Audiology) was calculated and reported. Other parameters were reported as normal or abnormal (in at least one ear) or inconclusive. Cameron S, Dillon H. The listening in spatialized noise-sentences test (LISN-S): comparison to the prototype LISN and results from children with either a suspected (central) auditory processing disorder or a confirmed language disorder. J Am Acad Audiol. 2008 May;19(5):377-91.

  Baseline

Secondary Outcomes (3)

• Correlation Between Clinically Obtained Imaging (Siderosis Group Participants) and the Hearing and Balance Assessment Results

  Baseline visit

• Correlation Between Clinically Obtained Results of Cognitive Function Assessment (Siderosis Group Participants) and the Hearing and Balance Assessments

  Baseline visit

• Smell Identification Test

  Baseline visit

Study Arms (3)

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

Diagnostic Test: Hearing assessment; Diagnostic Test: Vestibular/balance assessment; Other: Quality of life assessment; Diagnostic Test: Olfactory (smell) function testing; Genetic: 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)

Diagnostic Test: Hearing assessment; Other: Quality of life assessment

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)

Diagnostic Test: Hearing assessment; Other: Quality of life assessment

Interventions

Hearing assessment DIAGNOSTIC_TEST

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

Age-related hearing loss (ARHL) group; Control group; Siderosis (iSS) group

Vestibular/balance assessment DIAGNOSTIC_TEST

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

Siderosis (iSS) group

Quality of life assessment OTHER

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

Age-related hearing loss (ARHL) group; Control group; Siderosis (iSS) group

Olfactory (smell) function testing DIAGNOSTIC_TEST

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

Siderosis (iSS) group

DNA bio-banking GENETIC

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

Siderosis (iSS) group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Three groups of participants will be recruited into the study (as defined by the eligibility criteria): a) participants with a known diagnosis of iSS (siderosis group); b) participants with age-related hearing loss (ARHL group); c) participants with no previous history of hearing loss (control group).

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• University College, London: lead
• NIHR UCLH Biomedical Research Centre (BRC): collaborator
• Bernice Bibby Research Trust: collaborator

Study Sites (2)

UCL Ear Institute

London, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, United Kingdom

Location

Related Publications (14)

• 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.

  PMID: 28019651 BACKGROUND

• 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.

  PMID: 7655881 BACKGROUND

• 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.

  PMID: 8239558 BACKGROUND

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

  PMID: 17420310 BACKGROUND

• 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.

  PMID: 14406175 BACKGROUND

• 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.

  PMID: 21822983 BACKGROUND

• 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.

  PMID: 21730883 BACKGROUND

• 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.

  PMID: 8811680 BACKGROUND

• 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.

  PMID: 23670174 BACKGROUND

• 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.

  PMID: 14976664 BACKGROUND

• 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.

  PMID: 29889788 BACKGROUND

• 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.

  PMID: 8579152 BACKGROUND

• 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.

  PMID: 2006825 BACKGROUND

• 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.

  PMID: 15788543 BACKGROUND

Related Links

• WHO global estimates on prevalence of hearing loss

Biospecimen

Retention: SAMPLES WITH DNA

Saliva sampling to biobank the DNA for genetic analysis (siderosis group participants only). The samples will be labelled with a unique study code and will not contain identifiable information.

MeSH Terms

Conditions

Siderosis; Nervous System Diseases; Rare Diseases; Presbycusis; Hearing Loss; Ataxia

Interventions

Smell

Condition Hierarchy (Ancestors)

Pneumoconiosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Lung Injury; Occupational Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hearing Loss, Sensorineural; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Signs and Symptoms; Dyskinesias

Intervention Hierarchy (Ancestors)

Sensation; Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Limitations and Caveats

The tests were performed at baseline only. The major limitation to the study was the impact of COVID-19 pandemic on participant recruitment, availability of testing facilities and overall social restricions that were in place during the COVID-19 pandemic while the study was open.

Results Point of Contact

• Title: Dr N Kharytaniuk (Clinical Research Fellow)
• Organization: Ear Institute, University College London

n.kharytaniuk@ucl.ac.uk

02076792000

Study Officials

• Doris-Eva Bamiou, Professor

  UCL Ear Institute; UCLH NHS Foundation Trust, UK

  PRINCIPAL INVESTIGATOR

• David J Werring, Professor

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2019
• First Posted: December 16, 2019
• Study Start: February 7, 2020
• Primary Completion: October 19, 2021
• Study Completion: October 19, 2021
• Last Updated: June 10, 2025
• Results First Posted: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)