Study of Lamotrigine to Treat Ménière's Disease

Study Overview
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Brief Summary
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This double-blinded study evaluates the frequency of vertigo attacks and the quality of life of patients diagnosed with Ménière's disease after being randomly assigned to take a placebo or lamotrigine.

Official Title
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Lamotrigine for Ménière's Disease: a Double-blind, Placebo-controlled Pilot Study

Conditions
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Meniere's Disease, Ménière's Vertigo, Vertigo, Intermittent, Vertigo, Aural

Intervention / Treatment
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* Drug: Lamotrigine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female participants aged 18 years or older Diagnosed with unilateral definite Ménière's disease according to the AAO-HNS 1995 criteria, confirmed by an ENT Active vertigo: at least two Ménière's vertigo attacks (defined as lasting 20 minutes or longer and associated with tinnitus, ear fullness, or low frequency hearing loss and nausea/vomiting) every four weeks during the eight-week qualification period and at least two more Ménière's vertigo attacks during the lead-in phase prior to randomization Documented unilateral lower frequency hearing loss defined as the four-tone average (arithmetic mean rounded to the nearest whole number) of the pure-tone thresholds at 0.25, 0.5, 1 and 2 kilohertz (kHz) more than or equal to 25 decibels (dB) of the worse audiogram during the six months before screening Have tried diuretics for at least one month and discontinued treatment due to continued vertigo attacks All other co-existing medical or psychiatric conditions are stable, and no greater than moderate severity Willing to avoid pregnancy during the entirety of the study (abstinence or two forms of acceptable birth control, such as condoms and oral contraceptives) Exclusion Criteria: Bilateral Ménière's disease Current or past history of migraine Any other neuro-otologic disease or major vestibular abnormality found during screening that could confound the evaluation of Ménière's symptoms Previous intolerance or sensitivity to lamotrigine On any prohibited medication within four weeks prior to the study History of tympanostomy tubes with evidence of perforation or lack of closure IT gentamicin injections or endolymphatic sac surgery within the last year History of or current immunodeficiency disease, nephrolithiasis, hypertension, cardiac disease, arrhythmia, hypercholesterolemia, hemiplegic/basilar migraine, stroke, diabetes, vascular disease or kidney disease Family history of unexplained deafness Pregnant or breastfeeding Current diseases or conditions that may be associated with an altered perception of processing stimuli Current severe medical condition(s) that in the view of the investigator prohibits participation Previously used the investigational drug Current non-vertiginous dizziness (orthostatic or panic disorder) unless it could be clearly differentiated from Ménière's attacks by the participant

Ages Eligible for Study
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Minimum Age: 18 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>The placebo will match the lamotrigine dosage, frequency and duration. | Drug: Placebo<br>* The placebo will match the lamotrigine dosage, frequency and duration.<br>* Other names: microcrystalline cellulose;|
| Active Comparator: Lamotrigine<br>Lamotrigine will be taken orally for the duration of 20 weeks, consisting of a six-week titration, 12-week study period, and two-week taper. Possible doses are 25mg twice a day, 50mg twice a day, and 100 mg twice a day during titration; 150mg twice a day for the 12-week study period; 150mg once a day for Week 1 of the taper; and 75mg once a day for Week 2 of the taper. Patients who withdraw at any point of the study will have a two-week taper consisting of the current dose once a day for one week followed by half the dose once a day for another week. | Drug: Lamotrigine<br>* Lamotrigine will be taken orally on a daily basis for the duration of 20 weeks, consisting of a six-week titration, 12-week study period, and two-week taper. Possible doses for patients are 25mg twice a day, 50mg twice a day, and 100 mg twice a day during titration; 150mg twice a day for the 12-week study period; 150mg once a day for Week 1 of the taper; and 75mg once a day for Week 2 of the taper. Each increase in dose will be maintained for two weeks before deciding to further increase or decrease based on tolerability. Patients who discontinue at any point of the study will have a two-week taper consisting of the current dose once a day for one week followed by half the dose once a day for another week.<br>* Other names: U3H27498KS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Ménière's Vertigo Attack Frequency Between Lamotrigine and Placebo Group | Measured with a daily questionnaire | Duration of 12-week pre-treatment and 12-week study period (treatment) | 
| Change in Ménière's Vertigo Attack Frequency Within Lamotrigine Group | Measured with daily questionnaire | Duration of 12-week pre-treatment and 12-week study period (treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Ménière's Vertigo Attacks in Three-Week Intervals Between Lamotrigine and Placebo Groups | Measured with a daily questionnaire. | Duration of Week 16 to 18 | 
| Improvement in Pure Tone Average in the Affected Ear | Measured using the average of 500, 1000, 2000, and 3000 Hz presentation level (dB) | Prior to randomization and at completion of 12-week study period | 
| Improvement in Symptoms Severity | Based of rating on Clinical Global Impression of Change (CGI) score of blinded physician | 12-week pre-treatment period; 6 week titration; 12-week study period (treatment) | 
| DHI Scores | Dizziness Handicap Inventory (DHI). Minimum score=0. Maximum score=100. Higher scores mean a worse outcome. | Baseline (Week 1) and end of study (Week 18) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lamotrigine, Lamictal, Anticonvulsant, Ménière's disease, Vertigo attack, Dizziness, Vestibular disorder