SiderosisAViSSNCT04200664
Audiovestibular Function in Infratentorial Superficial Siderosis
An observational study of Siderosis and Neurological Disorder, run by University College, London at 2 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Siderosis, Neurological Disorder, Rare Diseases
- What is being tested?
- Hearing assessment, Vestibular/balance assessment and Quality of life assessment
- How many people
- 11 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 7 Feb 2020to 19 Oct 2021
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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).
Who may be able to join
- 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.
Who cannot join
- 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;
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
UCL Ear Institute
London
University College London Hospitals NHS Foundation Trust
London
About this study
Official title: Clinical and Imaging Biomarkers of Audiovestibular Function in Infratentorial Superficial Siderosis
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.
Read more
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.
Read the detailed description
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:
- People with iSS, who already have hearing and balance problems.
- People with age-related hearing loss, to compare how hearing declines over time.
- 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.
- Being tested
- Hearing assessment, Vestibular/balance assessment, Quality of life assessment, Olfactory (smell) function testing, DNA bio-banking
- Keywords
- Superficial siderosis, infratentorial, Nervous system diseases, Hearing loss, Hearing tests, Auditory pathways, Vestibulocochlear nerve, Ataxia, Vestibular function tests, Biomarkers, Central nervous system
- Medical subject headings
- Siderosis, Nervous System Diseases, Rare Diseases, Presbycusis, Hearing Loss, Ataxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hearing assessmentDiagnostic test
All study participants will undergo hearing tests, including hearing-specific questionnaires
Vestibular/balance assessmentDiagnostic test
Siderosis group participants will undergo vestibular/balance tests, including gait assessment and balance-specific questionnaires
Quality of life assessmentOther
All study participants will be asked to complete a set of quality of life questionnaires
Olfactory (smell) function testingDiagnostic 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-bankingGenetic
Siderosis group participants will be asked to provide a saliva sample for DNA bio-banking
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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) Receives: 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) Receives: Diagnostic Test: Hearing assessment; Other: Quality of life assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline visit
Vestibular/Balance Evaluation
Clinical vestibular and balance tests were performed to assess vestibular/balance function.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline
Secondary outcomes (3)
Correlation Between Clinically Obtained Imaging (Siderosis Group Participants) and the Hearing and Balance Assessment Results
Siderosis group participants underwent formal imaging procedures as part of their clinical care pathway. The imaging results were reviewed with the results obtained from hearing and vestibular/balance assessments. All participants had MRI Brain, as part of their clinical care pathway; susceptibility-weighted images were reviewed to identify the appearance of superficial siderosis, in keeping with the radiological diagnostic criteria (Reference: Wilson et al, 2017).
Measured: Baseline visit
Correlation Between Clinically Obtained Results of Cognitive Function Assessment (Siderosis Group Participants) and the Hearing and Balance Assessments
Siderosis group participants underwent a formal neuro-cognitive assessment as part of their clinical care pathway. The results of this clinical assessment were reviewed to determine if an association exists between the cognitive assessment results and the results obtained from hearing and vestibular/balance assessments performed during the study. A formal neuro-cognitive assessment was performed using the Wechsler Adult Intelligence Scale test. Cognitive impairment in a domain was defined as scoring at or below the fifth percentile on any one test in that domain.
Measured: Baseline visit
Smell Identification Test
University of Pennsylvania Smell Identification Test (UPSIT, British version) was performed (siderosis group participants) to assess their olfactory function. UPSIT is a forced-choice 40-item self-administered test. The scores are calculated using manufacturer's answer key as the sum of correct answers (maximum best = 40, minimum score 6; anosmia <19(males, females); normosmia >33 (males) and >34 (females)), and compared to the age- and gender-matched norms. The scores are also grouped into categories (ranging from normosmia to anosmia), with higher scores indicating better olfactory function.
Measured: Baseline visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2019
- Study start7 Feb 2020
- Primary completion19 Oct 2021
- Study completion19 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for SiderosisStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, Bernice Bibby Research Trust
- Responsible party
- Sponsor
- Investigators
- Doris-Eva Bamiou, Professor, Principal investigator, UCL Ear Institute; UCLH NHS Foundation Trust, UKDavid J Werring, Professor, Principal investigator, Stroke Research Centre UCL IoN; UCLH NHS Foundation Trust, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04200664
- Sponsor's protocol ID
- 121603
- Acronym
- AViSS
- Status last verified
- Jun 2025
- First submitted
- 10 Dec 2019
- Last updated
- 10 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The anonymised participant-level dataset and statistical code for generating the results will not be publicly available.
Publications
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.
PubMed 28019651Fearnley 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.
PubMed 7655881Koeppen 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.
PubMed 8239558Kumar N. Superficial siderosis: associations and therapeutic implications. Arch Neurol. 2007 Apr;64(4):491-6. doi: 10.1001/archneur.64.4.491.
PubMed 17420310IWANOWSKI 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.
PubMed 14406175Posti 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.
PubMed 21822983Sydlowski 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.
PubMed 21730883Offenbacher 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.
PubMed 8811680Sydlowski 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.
PubMed 23670174Vibert 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.
PubMed 14976664Takeda 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.
PubMed 29889788Pribitkin 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.
PubMed 8579152Kwartler 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.
PubMed 2006825van 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.
PubMed 15788543
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical and Imaging Biomarkers of Audiovestibular Function in Infratentorial Superficial Siderosis
- ClinicalTrials.gov ID
- NCT04200664
- Acronym / sponsor ID
- AViSS / 121603
- Keywords
- Superficial siderosis, infratentorial, Nervous system diseases, Hearing loss, Hearing tests, Auditory pathways, Vestibulocochlear nerve, Ataxia, Vestibular function tests
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, Bernice Bibby Research Trust
- Study start
- 7 Feb 2020 (actual)
- Primary completion
- 19 Oct 2021 (actual)
- Study completion
- 19 Oct 2021 (actual)
- First posted
- 16 Dec 2019 (actual)
- Results
- Posted 10 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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:
- People with iSS, who already have hearing and balance problems.
- People with age-related hearing loss, to compare how hearing declines over time.
- 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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Siderosis (iSS) group | – | Diagnostic Test: Hearing assessment, Diagnostic Test: Vestibular/balance assessment, Other: Quality of life assessment, Diagnostic Test: Olfactory (smell) function testing, Genetic: DNA bio-bankingparticipants 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 | – | Diagnostic Test: Hearing assessment, Other: Quality of life assessmentparticipants 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 | – | Diagnostic Test: Hearing assessment, Other: Quality of life assessmentparticipants 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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).
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hearing assessmentAll study participants will undergo hearing tests, including hearing-specific questionnaires | Diagnostic test | Age-related hearing loss (ARHL) group, Control group, Siderosis (iSS) group |
| Vestibular/balance assessmentSiderosis group participants will undergo vestibular/balance tests, including gait assessment and balance-specific questionnaires | Diagnostic test | Siderosis (iSS) group |
| Quality of life assessmentAll study participants will be asked to complete a set of quality of life questionnaires | Other | Age-related hearing loss (ARHL) group, Control group, Siderosis (iSS) group |
| Olfactory (smell) function testingSiderosis group participants will undergo a formal smell identification testing by means of self-administered smell chart to identify the revealed scents | Diagnostic test | Siderosis (iSS) group |
| DNA bio-bankingSiderosis group participants will be asked to provide a saliva sample for DNA bio-banking | Genetic | Siderosis (iSS) group |
Primary outcome
Hearing Evaluation - Pure Tone Audiometry
Time frame: Baseline visit
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.
Vestibular/Balance Evaluation
Time frame: Baseline visit
Clinical vestibular and balance tests were performed to assess vestibular/balance function.
Hearing Evaluation - Auditory Brainstem Responses/Acoustic Reflexes
Time frame: Baseline visit
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.
Hearing Evaluation - Tympanogram
Time frame: Baseline
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.
Hearing Evaluation - Otoacoustic Emissions
Time frame: Baseline
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.
Hearing Evaluation - Listening in Spatialised Sentences Noise Test
Time frame: Baseline
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.
3 secondary outcomes
Correlation Between Clinically Obtained Imaging (Siderosis Group Participants) and the Hearing and Balance Assessment Results
Time frame: Baseline visit
Correlation Between Clinically Obtained Results of Cognitive Function Assessment (Siderosis Group Participants) and the Hearing and Balance Assessments
Time frame: Baseline visit
Smell Identification Test
Time frame: Baseline visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28019651Wilson 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.
- Background: PubMed 7655881Fearnley 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.
- Background: PubMed 8239558Koeppen 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.
- Background: PubMed 17420310Kumar N. Superficial siderosis: associations and therapeutic implications. Arch Neurol. 2007 Apr;64(4):491-6. doi: 10.1001/archneur.64.4.491.
- Background: PubMed 14406175IWANOWSKI 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.
- Background: PubMed 21822983Posti 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.
- Background: PubMed 21730883Sydlowski 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.
- Background: PubMed 8811680Offenbacher 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.
- Background: PubMed 23670174Sydlowski 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.
- Background: PubMed 14976664Vibert 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.
- Background: PubMed 29889788Takeda 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.
- Background: PubMed 8579152Pribitkin 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.
- WHO global estimates on prevalence of hearing lossLink provided by the sponsor.
- Individual participant dataSharing planned: No. The anonymised participant-level dataset and statistical code for generating the results will not be publicly available.
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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.
Doris-Eva Bamiou, Professor principal investigator
UCL Ear Institute; UCLH NHS Foundation Trust, UK
David J Werring, Professor principal investigator
Stroke Research Centre UCL IoN; UCLH NHS Foundation Trust, UK
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Siderosis and Neurological Disorder, run by University College, London at 2 sites in United Kingdom.
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 3 inclusion and 4 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: finished, as of the sponsor's last update on 10 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Yes. Results are posted in the registry (first posted 10 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Hearing Evaluation - Pure Tone Audiometry (time frame: Baseline visit). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04200664, which also lists 14 linked publications.
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 10 Jun 2025.