The Effecttiveness of Intratympanic Methylprednisolon Injections Compared to Placebo in the Treatment of Vertigo Attacks in Meniere's Disease

Meniere Disease Clinical Trial

— PREDMEN  

Official title:

A Multicenter, Double-blinded, Randomized, Placebo-controlled Trial to Compare the Effectiveness of Intratympanic Injections methylPREDnisolon Versus Placebo in the Treatment of Vertigo Attacks in MENière's Disease (PREDMEN Trial).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05851508
• Other study ID #: PREDMEN
• Secondary ID: 10140022110009
• Status: Recruiting
• Phase: Phase 3
• Start date: October 1, 2023
• Est. completion date: February 1, 2027

Study information

• Verified date: November 2023
• Source: Leiden University Medical Center
• Contact: Maud Boreel, MD
• Phone: +3171 526 9111
• Email: m.m.e.boreel[@]lumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Ménière's disease is an inner ear disorder in which patients suffer from attacks of vertigo, tinnitus and hearing loss. To date, it is unclear what the best treatment for this condition is. Giving injections in the inner ear with the adrenal cortical hormone methylprednisolone is a treatment that is already widely used, but still there is insufficient evidence in the effectiveness of this treatment. This multicenter trial compares a patient group which receives injections of methylprednisolone to a patient group which receives placebo injections. Subsequently, dizziness, tinnitus, hearing loss and quality of life will be assed and compared for the above mentioned groups, over a period of one year.

Description:

Meniere's disease is an inner ear disease characterized by recurrent episodes of vertigo, hearing loss, tinnitus and aural fullness. It is estimated that 15000 patients in de Netherlands suffer from this disease. Endolymfactic hydrops is thought to be the underlying pathophysiology of the symptoms. Salt restriction, oral medication (diuretics and betahistine), intratympanic gentamicin and steroids, ablative surgery, and endolymphatic sac surgery are some of the current therapy options. A probable effectiveness of the treatment with intratympanic gentamicin is found but this treatment is ototoxic and carries a risk of hearing loss. Methylprednisolone injections have been shown to be safer, however there is insufficient data to support the efficacy of this treatment. Therefore in this double-blinded, randomized, placebo-controlled trial, effectiveness of intratympanic injections with methylPREDnisolon versus placebo in the treatment of vertigo attacks in MENière's disease is compared.

The investigators aim to include 74 patients in each arm, based on a statistical power of 80 percent. Patients will be randomly randomized to one of the two treatment arms, receiving either a placebo injection or a methylprednisolone sodium succinate injection at a dose of 62.5 mg/ml. After 14 days, this injection will be given once more. A follow-up visit will be scheduled after six and twelve months and telephone follow-up calls will be scheduled after three and nine months. The primary objective will be the control of vertigo, with secondary outcomes including hearing loss, tinnitus, the frequency of escape interventions, quality of life, adverse events and cost effectiveness.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 148
• Est. completion date: February 1, 2027
• Est. primary completion date: May 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion criteria:

• Unilateral, definite MD according to the diagnostic criteria derived from the American Academy Otolaryngology Head and Neck Surgery, Classification Committee of the Bárány Society, European Academy of Otology and Neurotology and International Classification of Vestibular Disorders published in 2015 [7] (see Appendix 1):

Definite MD Two or more spontaneous episodes of vertigo, each lasting 20 minutes to 12 hours, AND Audiometrically documented low- to medium-frequency sensorineural hearing loss in one ear, defining the affected ear on at least one occasion before, during or after one of the episodes of vertigo, AND Fluctuating aural symptoms (hearing, tinnitus, or fullness) in affected ear (not better accounted for by another vestibular diagnosis)

• age > 18 years at the start of the trial.

• = 4 vertigo attacks over the last 6 months.

• willing to adhere to daily trial medications and the follow-up assessments.

Exclusion criteria

A potential subject who meets any of the following criteria will be excluded:

• bilateral MD

• severe disability (e.g. neurological, orthopaedic, cardiovascular) or serious concurrent illness that might interfere with treatment or follow-up.

• active additional neuro-otologic disorders that may mimic MD (e.g. vestibular migraine, recurrent vestibulopathy, phobic postural vertigo, vertebro-basilar TIAs, acoustic neuroma).

• otitis media with effusion based on tympanogram results.

• history of intratympanic injections with corticosteroid less than 6 months ago.

• history of intratympanic injections with gentamicin or ear surgery for treating MD.

• pregnant women and nursing women.

Related Conditions & MeSH terms

• Meniere Disease
• Vertigo

Intervention

Drug:
• Methylprednisolon
Intratympanal injection with Methylprednisolon 62.5 mg/ ml
• Placebo
Intratympanal injection with saline, natriumchloride 0.9%

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Centre	Leiden	Zuid Holland

Sponsors (7)

Lead Sponsor	Collaborator
Leiden University Medical Center	Gelre Hospitals, HagaZiekenhuis, Maasstad Hospital, Maastricht University Medical Center, Medisch Spectrum Twente, ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vertigo spells	A definitive vertigo spell is defined as a spontaneous rotational vertigo symptom, which lasts at least 20 minutes and is often accompanied by disequilibrium and vomiting. No loss of consciousness is present. Vertigo spells are measured daily with the dizzy quest ap. Futhermore, at baseline after 6 and 12 months, caloric testing and a video-head impusle test are performend. Additionally the dizziness handicap inventory will be taken.	Daily, change from baseline to one year
Secondary	Hearing loss	Hearing loss will be measured at baseline, 6 and 12 months after injection. Pure tone audimetry and extended fletcher index including the speech discrimination score will be tested.	At baseline, 6 months and 12 months
Secondary	Tinnitus	Tinnitus will be measured with the tinnitus handicap inventory at baseline, after 6 and 12 months.	At baseline, 6 months and 12 months
Secondary	health-related quality of life	The health realted quality of life will be evaluated with the generic quality of life questionnaire: EQ-5D	At baseline, 6 months and 12 months
Secondary	health-related quality of life	The health realted quality of life will be evaluated with the generic quality of life questionnaire: EQ-VAS, this will be a scale from 0 to 100 in which 0 means the worst health you can imagine and 100 means the best health you can imagine	At baseline, 6 months and 12 months
Secondary	Escape medication	The frequency of use of metoclopramide in the acute phase of vertigo will be registered.	At baseline, 3 months, 6 months, 9 months, 12 months
Secondary	Adverse events	At each study visit, subjects will be questioned about adverse events they have experienced since the last study visit.	Daily, change from baseline to one year
Secondary	Cost-effectiveness	Costs per QALY, this will be calculated from above mentioned outcomes on quality of life.	At baseline, 6 months and 12 months
Secondary	Co-interventions	The use of additional methylprednisolon or gentamicine will be evaluated during the entire study.	Daily, change from baseline to one year
Secondary	Overall function	The functional level scale will be measured with the questionnaire: Functional level scale: a scale from 1-6 in which 1 means: my dizziness has no effect on my activities and 6 means: I have been disabled for one year or longer and/or I received compensation (money) because of y dizziness or balance problem.	At baseline, 6 months and 12 months
Secondary	Impact of Dizziness	The impact of dizziness will be measured with the questionnaire: Dizziness handicap inventory	Change from baseline to 6 months to 12 months
Secondary	Tinnitus severity	The tinnitus severety will be measured with the questionnaire: Tinnitus functional index	At baseline, 6 months and 12 months