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Worksheet Summary for Vestibular/Balance

(1) Based on data and experience, develop list of otologic conditions to be targeted in the next 5 to 10 years. Include rationale.
Disease/Disorder/ Condition/ Target	PH Significancee.g., high prevalence, severe dz, limited tx options	Treatment Optionse.g., none, ineffective, low benefit/risk ratio	Disease Severitye.g., dire consequences, dire disabilities, compromised QOL	Evidence Base e.g., none, some, limited	Stage of readiness for research involving humans
Meniere's disease	Very high	Unknown efficacy; many treatments are used but comparisons with one another and comparisons to natural history of disease are very slim	Very debilitating in many people, compromised QOL.	Very limited	Areas that are ready immediately: Epidemiology Registry Stringent criteria Databank Genome-based association studies Diagnostic studies Imaging – MRI VEMP ECOG DPOEs
Age-related vestibular dysfunction	Likely to be very high; contribution to falls in the elderly which have enormous mortality and economic impact	Physical therapy, possible Vestibular Implant	Likely to be very high	Very limited; some studies that do demonstrate loss of hair cells and Scarpa’s ganglion cells with age; also studies that show decline in VOR with age	Areas that are ready immediately: Epidemiology Determination of peripheral vs. central etiology Genome-based association studies Analysis of RFs for falls
Migraine and vestibular dysfunction	Very high	Unknown and/or limited efficacy	Can be very severe and debilitating	Very limited; genetics of some forms of migraine are known but relationship to vestibular symptoms is unknown	Areas that are ready immediately: Epidemiology Peripheral and/or central origin Genome-based association studies
Incomplete compensation for vestibular hypofunction	Very high	Unknown and/or limited efficacy Role for PT Vestibular implant	Can be very severe	Very limited; Role of co-morbidity remains to be determined	Areas that are ready immediately: Studies of vestibular dysfunction and balance associated with: Radiation for AN IT gentamicin Labyrinthectomy AN surgery Trauma
Superior semicircular canal dehiscence	Prevalence is currently unknown; has relevance to understanding other disorders of the ear	Surgical repair; indications are being determined and outcomes monitored	Can be very disabling	Physiological evidence of effects of dehiscence on vestibular function is strong; Underling cause is unknown	Areas that are ready immediately: Diagnostic testing Genome-based association studies
Autoimmune inner ear disease – vestibular dysfunction	Prevalence relatively low but impact on understanding other disorders of the ear is high	Efficacy of steroids has been established; other treatments still in investigational status	Can be very disabling	Evidence exists for autoimmune etiology; underlying cause is unknown	Areas that are ready immediately: Diagnostic testing Genome-based association studies

(2) For each target otologic condition, categorize the current state of knowledge regarding the condition and its interventions(if any) and the stage of research necessary for full development of the intervention.
Disease/Disorder/ Condition/ Target	Understanding of Dz/Disorder/ Condition e.g., natural hx, treatment altering natural course	Understanding of patho-physiology	Is there a therapeutic target	Describe intervention: any modality e.g., surgery, drug, device, drug, behavior	Stage of development of intervention e.g., basic understanding/early translation, preclinical, clinical, definitive clinical trials, late translation
Meniere’s disease	Incomplete – natural history is variable and needs to be more carefully studied	Incomplete – approach that involves identification of candidate genes and studies of vestibular effects of knockouts of these genes in mice may be useful	Not clear at present time	Staged approach to treatment: low salt, life style diuretic steroids, gentamicin	Basic understanding May be the time for analyses of staged approaches to treatment Animal model representative of pathophysiology is needed Improved diagnostic tests
Age-related vestibular dysfunction	Incomplete – interactions of peripheral and central disorders is inadequate	Incomplete – need to integrate approaches to studies of balance function	Yes. e.g., Loss of vestibular function due to hair cell and ganglion cell death	Regeneration medicine Vestibular implant	Basic understanding Animal models Improved diagnostic tests Analysis of RFs for falls
Migraine and vestibular dysfunction	Incomplete	Very incomplete	Not at present		Basic understanding Epidemiology Gene association studies
Incomplete compensation for vestibular hypofunction	Different disorders result in vestibular hypofunction	Incomplete	Not at present	Regeneration Vestibular implant	Basic understanding of vestibular compensation
Superior semicircular canal dehiscence	Effects of dehiscence on vestibular function have been described	Cause of dehiscence and thinning is incomplete	Not at present		Diagnostic testing Gene association studies
Autoimmune inner ear disease – vestibular dysfunction	Natural history has been described for hearing loss; effects on vestibular function are unclear	Pathophysiology is not understood at level of immunologic dysfunction or hair cell/afferent disorder	Not at present	Regeneration Vestibular implant	Diagnostic testing Gene association studies

Common Themes:

Need to improve vestibular diagnostic tests:
Need better understanding of epidemiology across all vestibular pathologies.
Need for gene association studies for many vestibular pathologies.
Need for validated outcome measures in dizziness and balance disorders. Something analogous to Stage 1 behavioral study. It would be appropriate for these validated outcome measures to be developed before large-scale clinical trials.

Possible consideration:

Establish a Meniere’s disease ‘registry’ which involves multiple centers with agreed upon criteria for assessment of symptoms, stage of the disease, vestibular function, auditory function, and follow-up. Gene association studies to be performed on patients who enter the study. This registry and the centers involved will enable us to study the natural history of Meniere’s disease. We recommend beginning with a group of established centers with recognized expertise in Meniere’s disease. As a part of the development of this registry, standardized criteria will be developed by investigator’s participating in the registry for diagnosis, evaluation, and follow-up. This registry will then serve as the basis for future therapeutic intervention trials. This registry could, in the future, be opened for enrollment of patients by any practitioner who treats patients with Meniere’s disease.