Clinical trial NCT04200664: Audiovestibular Function in Infratentorial Superficial Siderosis
Official title: Clinical and Imaging Biomarkers of Audiovestibular Function in Infratentorial Superficial Siderosis
Study type: OBSERVATIONAL
Overall status: COMPLETED
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
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: NIHR UCLH Biomedical Research Centre (BRC)
name: Bernice Bibby Research Trust
First posted: 2019-12-16
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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).

Brief summary: One in six people in the United Kingdom and over 400 million people worldwide have disabling hearing loss. This figure will double by 2050 as predicted by the World Health Organisation. There is an urgent need to improve our knowledge regarding hearing loss, its underlying mechanisms, optimal diagnostic modalities, reliable and accurate functional and imaging biomarkers.

A less-well studied condition associated with progressive hearing loss is infratentorial superficial siderosis (iSS). It results from iron deposition along the surfaces of brain structures which control hearing and balance. It is currently considered uncommon, but may well be under-recognised and therefore under-reported. Despite its severity, our current understanding of its impact on the hearing (auditory) and balance (vestibular) functions is limited, and this has an adverse impact on the treatment offered to these patients. Additionally, iSS patients have been reported to have cognitive impairment yet literature reports of cognitive assessment in iSS are few. The cognitive dysfunction may be specific to iSS or due to progressive hearing impairment or a combination of both, and further studies are required to establish this. Olfaction is also known to be affected in patients with iSS yet is rarely reported in the literature.

Due to the significant morbidity and progressive nature, there is a clear need to improve our understanding of the audiovestibular dysfunction resulting from iSS.

The aim of this study is to comprehensively assess audiovestibular function in iSS compared to age-related hearing loss and the controls/normative data and as a means to quantify deficits for monitoring disease progression and response to treatment, to assess the impact on the quality of life, to analyse clinically-obtained data (including imaging, cognitive and laboratory data), and correlate these with functional findings in iSS.

Detailed description: 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.

Eligibility criteria: 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;

Primary outcomes:
measure: Hearing Evaluation - Pure Tone Audiometry
timeFrame: Baseline visit
measure: Vestibular/Balance Evaluation
timeFrame: Baseline visit
measure: Hearing Evaluation - Auditory Brainstem Responses/Acoustic Reflexes
timeFrame: Baseline visit
measure: Hearing Evaluation - Tympanogram
timeFrame: Baseline
measure: Hearing Evaluation - Otoacoustic Emissions
timeFrame: Baseline
measure: Hearing Evaluation - Listening in Spatialised Sentences Noise Test
timeFrame: Baseline
Secondary outcomes:
measure: Correlation Between Clinically Obtained Imaging (Siderosis Group Participants) and the Hearing and Balance Assessment Results
timeFrame: Baseline visit
measure: Correlation Between Clinically Obtained Results of Cognitive Function Assessment (Siderosis Group Participants) and the Hearing and Balance Assessments
timeFrame: Baseline visit
measure: Smell Identification Test
timeFrame: Baseline visit
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: UCL Ear Institute
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
Study officials:
affiliation: UCL Ear Institute; UCLH NHS Foundation Trust, UK
name: Doris-Eva Bamiou, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Stroke Research Centre UCL IoN; UCLH NHS Foundation Trust, UK
name: David J Werring, Professor
role: PRINCIPAL_INVESTIGATOR
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