Acute Unilateral Vestibulopathy and Corticosteroid Treatment

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.

Study Overview

• Status: Terminated
• Conditions: Vestibular Diseases; Vestibular Neuronitis
• Intervention / Treatment: Drug: Placebo; Drug: Betamethasone; Drug: Prednisolone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 4

Contacts and Locations

Study Locations

• Sweden
  • Helsingborg, Sweden
    • Dept OtoRhinoLaryngology
  • Kristianstad, Sweden
    • Dept. Otorhinolaryngology
  • Lund, Sweden, 22185
    • Dept. OtoRhinoLaryngology Head and Neck Surgery, Skane University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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; Placebo intravenous NaCl intravenous administration Placebo tablets; Other Names: Sodiumchloride
Active Comparator: Short treatment; 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; Betamethasone intravenous; Other Names: Betapred; Drug: Prednisolone; Oral tablets; Other Names: Prednisolon
Active Comparator: Standard treatment; 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; Betamethasone intravenous; Other Names: Betapred; Drug: Prednisolone; Oral tablets; Other Names: Prednisolon

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Lund University
• Investigators: Principal Investigator: Fredrik Tjernström, MD, PhD, Lund University

Publications and helpful links

General Publications

• Fishman JM, Burgess C, Waddell A. Corticosteroids for the treatment of idiopathic acute vestibular dysfunction (vestibular neuritis). Cochrane Database Syst Rev. 2011 May 11;(5):CD008607. doi: 10.1002/14651858.CD008607.pub2.
• Strupp M, Zingler VC, Arbusow V, Niklas D, Maag KP, Dieterich M, Bense S, Theil D, Jahn K, Brandt T. Methylprednisolone, valacyclovir, or the combination for vestibular neuritis. N Engl J Med. 2004 Jul 22;351(4):354-61. doi: 10.1056/NEJMoa033280.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: September 15, 2016
• First Submitted That Met QC Criteria: September 20, 2016
• First Posted (Estimate): September 23, 2016

Study Record Updates

• Last Update Posted (Actual): September 10, 2021
• Last Update Submitted That Met QC Criteria: September 2, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Otorhinolaryngologic Diseases; Labyrinth Diseases; Ear Diseases; Cranial Nerve Diseases; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Vestibular Diseases; Vestibular Neuronitis; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Anti-Asthmatic Agents; Respiratory System Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Betamethasone
• Other Study ID Numbers: VN-FT-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No