Study of Lamotrigine to Treat Ménière's Disease

Phase 2

Completed

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

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	The placebo will match the lamotrigine dosage, frequency and duration.
Lamotrigine	Lamotrigine	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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