Study of Lamotrigine to Treat Ménière's Disease

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

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.

Study Overview

• Status: Completed
• Conditions: Meniere's Disease; Ménière's Vertigo; Vertigo, Intermittent; Vertigo, Aural
• Intervention / Treatment: Drug: Placebo; Drug: Lamotrigine

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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
Placebo Comparator: Placebo; The placebo will match the lamotrigine dosage, frequency and duration.	Drug: Placebo; The placebo will match the lamotrigine dosage, frequency and duration.; Other Names: microcrystalline cellulose
Active Comparator: 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.	Drug: Lamotrigine; 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.; Other Names: Lamictal; 3,5-diamino-6-(2,3-dichlorophenyl)-as-triazine; U3H27498KS

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Dent Neuroscience Research Center
• Collaborators: University at Buffalo
• Investigators: Principal Investigator: Lixin Zhang, MD, PhD, Dent Neurologic Institute

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: June 2, 2014
• First Submitted That Met QC Criteria: June 5, 2014
• First Posted (Estimate): June 9, 2014

Study Record Updates

• Last Update Posted (Actual): June 22, 2022
• Last Update Submitted That Met QC Criteria: May 26, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Lamotrigine; Dizziness; Anticonvulsant; Lamictal; Ménière's disease; Vertigo attack; Vestibular disorder
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Labyrinth Diseases; Ear Diseases; Vestibular Diseases; Sensation Disorders; Endolymphatic Hydrops; Vertigo; Dizziness; Meniere Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anticonvulsants; Sodium Channel Blockers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Lamotrigine
• Other Study ID Numbers: Zhang-001