An observational study in Siderosis, Neurological Disorder and Rare Diseases, sponsored by University College, London. Completed at 2 sites in United Kingdom. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-06-10.
Sponsored by University College, London · Observational
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.
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:
The study will take place over three years, using a range of tests to assess hearing and balance:
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.
66 studies on the registry are indexed under Presbycusis; 21 are open to participants now.
This study's enrollment of 11 is below the median of 123 across 20 observational studies indexed under Presbycusis.
Browse Presbycusis studies →University College, London is the lead sponsor of 651 studies on the registry; 149 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 2 (33%) have results posted.
Compared within Presbycusis, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Nervous System Diseases. The counts are of registry records indexed under each term, refreshed daily. How we classify →
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).
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
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
All study participants will undergo hearing tests, including hearing-specific questionnaires
Siderosis group participants will undergo vestibular/balance tests, including gait assessment and balance-specific questionnaires
All study participants will be asked to complete a set of quality of life questionnaires
Siderosis group participants will undergo a formal smell identification testing by means of self-administered smell chart to identify the revealed scents
Siderosis group participants will be asked to provide a saliva sample for DNA bio-banking
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.
Time frame: Baseline visit
Vestibular/Balance Evaluation
Clinical vestibular and balance tests were performed to assess vestibular/balance function.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline
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).
Time frame: 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.
Time frame: 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.
Time frame: Baseline visit
Of the 90 anticipated participants, only 11 participants were recruited to the study - into the Siderosis group. Participants were not recruited into the non siderosis groups (ie Age-Related Hearing Loss group and Control group) due COVID19 restrictions at the time of the study, which impacted significantly on recruitment opportunities and dramatically reduced the participant number in the study.
| Milestone | Siderosis (iSS) Group | Age-related Hearing Loss (ARHL) Group | Control Group |
|---|---|---|---|
| Started | 11 | 0 | 0 |
| Completed | 10 | 0 | 0 |
| Not completed | 1 | 0 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 | 0 |
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.
| decibel hearing level | Siderosis (iSS) Group |
|---|---|
| Hearing Evaluation - Pure Tone Audiometry | 57.3 ± 39.9 |
Clinical vestibular and balance tests were performed to assess vestibular/balance function.
| Participants | Siderosis (iSS) Group |
|---|---|
| Video head impulse test — Abnormal | 6 |
| Video head impulse test — Normal | 1 |
| Video head impulse test — Not tested | 3 |
| Video- electro-nystagmography (oculomotor; rotatory chair) - central vestibular assessment — Abnormal | 9 |
| Video- electro-nystagmography (oculomotor; rotatory chair) - central vestibular assessment — Normal | 1 |
| Video- electro-nystagmography (oculomotor; rotatory chair) - central vestibular assessment — Not tested | 0 |
| Video- electronystagmography (oculomotor; rotatory chair) - peripheral vestibular assessment — Abnormal | 7 |
| Video- electronystagmography (oculomotor; rotatory chair) - peripheral vestibular assessment — Normal | 3 |
| Video- electronystagmography (oculomotor; rotatory chair) - peripheral vestibular assessment — Not tested | 0 |
| Bithermal calorics — Abnormal | 1 |
| Bithermal calorics — Normal | 2 |
| Bithermal calorics — Not tested | 7 |
| ocular Vestibular Evoked Myogenic Potentials — Abnormal | 0 |
| ocular Vestibular Evoked Myogenic Potentials — Normal | 9 |
| ocular Vestibular Evoked Myogenic Potentials — Not tested | 1 |
| cervical Vestibular Evoked Myogenic Potentials — Abnormal | 3 |
| cervical Vestibular Evoked Myogenic Potentials — Normal | 7 |
| cervical Vestibular Evoked Myogenic Potentials — Not tested | 0 |
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.
| Participants | Siderosis (iSS) Group |
|---|---|
| Abnormal | 5 |
| Inconclusive | 2 |
| Not performed | 4 |
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.
| Participants | Siderosis (iSS) Group |
|---|---|
| Abnormal | 0 |
| Normal | 11 |
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.
| Participants | Siderosis (iSS) Group |
|---|---|
| Present | 3 |
| Absent | 3 |
| Not performed | 5 |
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.
| Participants | Siderosis (iSS) Group |
|---|---|
| Abnormal | 4 |
| Normal | 1 |
| Not tested | 6 |
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).
| Participants | Siderosis (iSS) Group |
|---|---|
| Superior cerebellar vermis — Hypointense signal consistent with superficial siderosis observed | 10 |
| Superior cerebellar vermis — Hypointense signal consistent with superficial siderosis not observed | 0 |
| Cerebellar folia — Hypointense signal consistent with superficial siderosis observed | 10 |
| Cerebellar folia — Hypointense signal consistent with superficial siderosis not observed | 0 |
| Midbrain — Hypointense signal consistent with superficial siderosis observed | 10 |
| Midbrain — Hypointense signal consistent with superficial siderosis not observed | 0 |
| Pons — Hypointense signal consistent with superficial siderosis observed | 9 |
| Pons — Hypointense signal consistent with superficial siderosis not observed | 1 |
| Medulla — Hypointense signal consistent with superficial siderosis observed | 9 |
| Medulla — Hypointense signal consistent with superficial siderosis not observed | 1 |
| 8th cranial nerve (unilateral or bilateral) — Hypointense signal consistent with superficial siderosis observed | 9 |
| 8th cranial nerve (unilateral or bilateral) — Hypointense signal consistent with superficial siderosis not observed | 1 |
| Supratentorial extension — Hypointense signal consistent with superficial siderosis observed | 10 |
| Supratentorial extension — Hypointense signal consistent with superficial siderosis not observed | 0 |
| Sylvian fissures — Hypointense signal consistent with superficial siderosis observed | 9 |
| Sylvian fissures — Hypointense signal consistent with superficial siderosis not observed | 1 |
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.
| Participants | Siderosis (iSS) Group |
|---|---|
| Participants who underwent neurocognitive assessment | 7 |
| Executive function abnormal | 5 |
| Visual memory abnormal | 5 |
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.
| UPSIT score | Siderosis (iSS) Group |
|---|---|
| Smell Identification Test | 25.5 ± 7.8 |
Collected over Up to one hour at baseline. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Siderosis (iSS) Group | 0/11 (0%) | 0/11 (0%) | 0/11 (0%) |
Individuals with known/confirmed diagnosis of infratentorial classical superficial siderosis under the care of clinical team at the UCLH NHS Foundation Trust, UK.
| Age, Customized(years) | Siderosis (iSS) Group |
|---|---|
| Mean | 52.5 ± 14.5 |
| Sex: Female, Male(Participants) | Siderosis (iSS) Group |
|---|---|
| Female | 2 |
| Male | 8 |
| Race and Ethnicity Not Collected(Participants) | Siderosis (iSS) Group |
|---|
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No — The anonymised participant-level dataset and statistical code for generating the results will not be publicly available.
Ran from Feb 2020 to primary completion in Oct 2021, 20 months.
Results were first posted in Jun 2025, 3 years 7 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jun 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.