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

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).

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.

Study Overview

• Status: Recruiting
• Conditions: Meniere Disease
• Intervention / Treatment: Drug: Methylprednisolon; Drug: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 148
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Maud Boreel, MD; Phone Number: +3171 526 9111; Email: m.m.e.boreel@lumc.nl
• Study Contact Backup: Name: Babette van Esch, MD, PHD; Phone Number: +3171 526 9111; Email: b.f.van_esch@lumc.nl

Study Locations

• Netherlands
  • Zuid Holland
    • Leiden, Zuid Holland, Netherlands, 2300RC
      • Recruiting
      • Leiden University Medical Centre
      • Contact: Maud Boreel, Msc; Phone Number: +31647682120; Email: m.m.e.boreel@lumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Methylprednisolon; Intratympanal injection with Methylprednisolon 62.5 mg/ ml	Drug: Methylprednisolon; Intratympanal injection with Methylprednisolon 62.5 mg/ ml
Placebo Comparator: Placebo; Intratympanal injection with saline, natriumchloride 0.9%	Drug: Placebo; Intratympanal injection with saline, natriumchloride 0.9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Tinnitus	Tinnitus will be measured with the tinnitus handicap inventory at baseline, after 6 and 12 months.	At baseline, 6 months and 12 months
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
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
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
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
Cost-effectiveness	Costs per QALY, this will be calculated from above mentioned outcomes on quality of life.	At baseline, 6 months and 12 months
Co-interventions	The use of additional methylprednisolon or gentamicine will be evaluated during the entire study.	Daily, change from baseline to one year
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
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
Tinnitus severity	The tinnitus severety will be measured with the questionnaire: Tinnitus functional index	At baseline, 6 months and 12 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2023
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: February 20, 2023
• First Submitted That Met QC Criteria: May 1, 2023
• First Posted (Actual): May 9, 2023

Study Record Updates

• Last Update Posted (Estimated): December 4, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: randomized control trial; Dizziness; tinnitus; Hearing loss; Meniere's disease; Methylprednisolon; Intratimpanic corticosteroids; aural fullness
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Labyrinth Diseases; Ear Diseases; Vestibular Diseases; Endolymphatic Hydrops; Vertigo; Meniere Disease; 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; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: PREDMEN; 10140022110009 (Other Grant/Funding Number: ZonMW)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual patient data after deidentification will be shared upon reasonable request with researchers who provide a methodologically sound proposal. For analyses to achieve aims as described in the approved proposal.
• IPD Sharing Time Frame: Data will be accessible after publication of the data
• IPD Sharing Access Criteria: Data can be shared upon reasonable request for multiple purposes. Proposals should be directed to M.M.E.Boreel@lumc.nl. To share data we will use the data transfer agreement in line with the template provided by the LUMC
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No