Acute Unilateral Vestibulopathy and Corticosteroid Treatment

Study Overview
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Brief Summary
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Randomized placebo controlled trial on patients suffering from acute unilateral vestibulopathy. Patients will be randomized into 3 arms; 1) Placebo only, 2) Short corticosteroid treatment (3days) 3) Longer corticosteroid treatment (11 days). Vestibular function as well as subjective symptoms will be estimated in the acute stage and regularly up to one year after the debut.

Detailed Description
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Randomized controlled trial in 3 arms to see if a short or a even shorter period of steroid treatment on patients diagnosed with vestibular neuritis can be as effective as the only comparable study thus far (Strupp et al, NEJM 22, 351(4) 354-61). If a shorter treatment with a lower dose has the same outcome, then more patients might be eligible for the treatment as many are excluded due to risk for adverse effects. Corticosteroid treatment in acute unilateral vestibulopathy has recently been the subject for a Cochrane review with the conclusion of insufficient evidence for treatment effect and recommend studies with subjective symptom based evaluation together with functional testing. Patients with acute unilateral vestibulopathy diagnosed within 48hrs after debut. The patients (after acceptance) will be randomized into either of 3 arms and will receive placebo/short treatment (3days)/standard treatment (in Sweden 11 days). Patients will record subjective symptoms according to Liknert scale during the acute stage and fill out enquiries after 3 and 12 months. Vestibular function will be assessed with caloric irrigation and video-Head-Impulse-Test (vHIT) as soon as possible after the debut and again after 1, 3 and 12 months.

Official Title
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Acute Unilateral Vestibulopathy and Corticosteroid Treatment

Conditions
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Vestibular Diseases, Vestibular Neuronitis

Intervention / Treatment
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* Drug: Betamethasone
* Drug: Placebo
* Drug: Prednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: definite unilateral vestibulopathy no pathological HINTS (examination criteria in acute vestibular syndrome) capable of making their own decisions Exclusion Criteria: tinnitus or hearing loss with same debut as vertigo history of bleeding peptic ulcer glaucoma pregnancy or non-acceptance to use anticonception measures during 13 days after debut high blood pressure >180 systolic, 105, diastolic ketoacidosis with a Base Excess >=2 psychic disorder (not including mild depression) serious infection (neutropenia, tuberculosis) chronic otitis history of vertiginous disease; Ménière, Vertiginous migraine, atypical BPPV

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Day 1: Intravenous sodium-chloride 2ml Day 2-6: 10 tablets placebo Day 7: 8 tablets placebo Day 8: 6 tablets placebo Day 9: 4 tablets placebo Day 10: 2 tablets placebo Day 11: 1 tablet placebo | Drug: Placebo<br>* Placebo intravenous NaCl intravenous administration Placebo tablets<br>* Other names: Sodiumchloride;|
| Active Comparator: Short treatment<br>Day 1: Intravenous betamethasone 8mg (2ml of 4mg/ml) Day 2-3: 10 tablets prednisolone 5 mg Day 4-6: 10 tablets placebo Day 7: 8 tablets placebo Day 8: 6 tablets placebo Day 9: 4 tablets placebo Day 10: 2 tablets placebo Day 11: 1 tablet placebo | Drug: Betamethasone<br>* Betamethasone intravenous<br>* Other names: Betapred;Drug: Prednisolone<br>* Oral tablets<br>* Other names: Prednisolon;|
| Active Comparator: Standard treatment<br>Day 1: Intravenous betamethasone 8mg (2ml of 4mg/ml) Day 2-6: 10 tablets prednisolone 5 mg Day 7: 8 tablets prednisolone 5 mg Day 8: 6 tablets prednisolone 5 mg Day 9: 4 tablets prednisolone 5 mg Day 10: 2 tablets prednisolone 5 mg Day 11: 1 tablet prednisolone 5 mg | Drug: Betamethasone<br>* Betamethasone intravenous<br>* Other names: Betapred;Drug: Prednisolone<br>* Oral tablets<br>* Other names: Prednisolon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Caloric function | Warm (44deg C) and cold (30 deg C) water irrigation of the ear canals of both ears. Jongkees formula (ratio of response between the ears) is assessed for abnormal or normal function | after 3 months | 
| Caloric function | Warm (44deg C) and cold (30 deg C) water irrigation of the ear canals of both ears. Jongkees formula (ratio of response between the ears) is assessed for abnormal or normal function | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| vHIT | measurement of vestibulo-ocular reflex in all semicircular canals. Gain <0.7 (ratio between head and eye movement) is regarded as pathological | 2-5 days after debut | 
| Subjective visual vertical/horizontal | Assessment of spatial orientation or utricular function (of the inner ear) as a measure of degree of vestibular loss and of compensation | 2-5 days after debut, | 
| Covert saccades | Covert catch-up eye saccades are sometimes seen during vHIT. The origin is unknown. The frequency as well as latency times will be analyzed and correlated to subjective measures | 2-5 days after debut, | 
| Vertigo Diary | Self-assessment of vertigo according to a Liknert scale daily (1= no vertigo and 10= worst possible vertigo | Daily from debut and until no subjective vertigo is experienced, longest 4 weeks | 
| Sleep Diary | Patients often experience troubled sleep when treated with corticosteroids. How much has not been assessed. The patients will assess their sleep the previous night according to a Liknert scale (1=good nights sleep, 10=hardly slept at all) | Daily from debut and 14 days onwards (2 days after last treatment) | 
| HADS-enquiry | Hospital Anxiety and Depression Scale. To asses the degree of anxiety and depression among the patients, often associated with chronic dizziness | 3 and 12 months after debut | 
| VSS-enquiry | Vertigo sympton score, To assess vertigo symptoms | 3 and 12 months after debut | 
| DHI-enquiry | Dizziness Handicap Inventory, to assess the degree of how dizziness affect daily life | 3 and 12 months after debut | 
| VHQ-enquiry | Vertigo Handicap Questionnaire. To assess the degree of how vertigo affect daily life | 3 and 12 months after debut | 
| Stress hormones | Measurement of Plasma thyroid hormones, adrenocorticoid hormones (ACTH, Cortisone) as stress indicators in acute vertigo. Baseline will be taken 1 year after debut | At debut and 1 year | 
| Saliva-Cortisol | Daily measurement of saliva cortisol as measurement of stress | At debut and up to 1 week | 
| Adverse Events | Analysis of adverse events to treatment as well as functional outcome | From debut to 1 year after | 
| Hospital stay | Duration of hospital stay | From debut up to 10 days | 
| vHIT | measurement of vestibulo-ocular reflex in all semicircular canals. Gain <0.7 (ratio between head and eye movement) is regarded as pathological | 1 year | 
| Subjective visual vertical/horizontal | Assessment of spatial orientation or utricular function (of the inner ear) as a measure of degree of vestibular loss and of compensation | 1 month | 
| Subjective visual vertical/horizontal | Assessment of spatial orientation or utricular function (of the inner ear) as a measure of degree of vestibular loss and of compensation | 3 months | 
| Subjective visual vertical/horizontal | Assessment of spatial orientation or utricular function (of the inner ear) as a measure of degree of vestibular loss and of compensation | 1 year | 
| Covert saccades | Covert catch-up eye saccades are sometimes seen during vHIT. The origin is unknown. The frequency as well as latency times will be analyzed and correlated to subjective measures | 3 months | 
| Covert saccades | Covert catch-up eye saccades are sometimes seen during vHIT. The origin is unknown. The frequency as well as latency times will be analyzed and correlated to subjective measures | 1 year | 
| Sick-leave | Time needed for sick-leave | debut up to 1 year | 
| Daily living | Time until daily activities are as prior to th disease | debut up to 1 year |