Lamotrigine and Bupropion for Meniere's Disease

A Randomized, Prospective, Double-Blind, Placebo-Controlled, Pilot Study to Assess the Effectiveness of a Combination of Lamotrigine and Bupropion to Treat Meniere's Disease

This is a double-blind, placebo-controlled clinical trial to assess whether treatment with lamotrigine and bupropion is more effective than placebo to reduce definitive Meniere's vertigo attacks (DMVA) and dizziness in patients with Meniere's disease. Thirty four participants will be randomized to treatment or placebo groups. Each participant will take part in the trial for 34 weeks, or approximately 9 months.

Study Overview

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

Detailed Description

Participants begin with a 4 week lead-in after screening to determine the frequency and severity of vertigo they are experiencing. Participants continue to track their vertigo episodes throughout the study. At Visit 2, if eligible, participants begin the titration of lamotrigine or matching placebo. Participants are on the full dose of lamotrigine/placebo for 8 weeks, and then begin taking bupropion or matching placebo along with lamotrigine or matching placebo for 12 weeks. At Week 27, participants are tapered off lamotrigine/placebo and stop taking bupropion/placebo. Participants have an in-person visit approximately once a month over 9 months.

• Study Type: Interventional
• Enrollment (Anticipated): 34
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Maxwell Kahn, JD; Phone Number: 716-250-7002; Email: mkahn@dentinstitute.com
• Study Contact Backup: Name: Dawn Pytlik; Phone Number: 716-250-3083; Email: dpytlik@dentinstitute.com

Study Locations

• United States
  • New York
    • Amherst, New York, United States, 14226
      • Recruiting
      • Dent Neurologic Institute
      • Contact: Maxwell Kahn, JD; Phone Number: 716-250-7002; Email: mkahn@dentinstitute.com
      • Contact: Dawn Pytlik, AAS; Phone Number: 716-250-3083; Email: dpytlik@dentinstitute.com
      • Principal Investigator: Lixin Zhang, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult participants, male and female aged 18 years or older
• Diagnosis of definitive unilateral Meniere's disease according to the AAO-HNS 1995 criteria, confirmed by an ENT or qualified medical professional
• Be experiencing active vertigo
• Be in good general health as evidenced by medical history or, otherwise, have all other co-existing medical or psychiatric conditions stable, and or no greater than moderate in severity, as determined by the PI
• Females of childbearing potential must use at least two forms of acceptable contraception, or remain abstinent; male participants must be willing to use condoms or other methods to ensure effective contraception with a partner
• Be willing to comply with all study procedures and availability for the duration of the study
• Be able to provide informed written consent, including agreement to privacy language either within the informed consent or in ancillary documents compliant with Health Insurance Portability and Accountability Act (HIPAA) before the initiation of any study-related procedures

Exclusion Criteria:

• A diagnosis of bilateral Meniere's disease according to the AAO-HNS 1995 criteria, confirmed by an ENT or qualified medical professional
• Be pregnant or lactating
• Have active migraine-associated vertigo
• Not be able to accurately identify and report episodes of vertigo
• Diagnosis of any other neuro-otologic disease or major vestibular abnormality found during screening that could confound the evaluation of Meniere's symptoms
• Have a history of intolerance or sensitivity to lamotrigine
• Previously failed the study drug
• Received an intratympanic gentamicin injection(s) or endolymphatic sac surgery within in the last year
• Have a family history of unexplained deafness
• Have any current diseases or conditions that may be associated with an altered perception of processing stimuli
• Have a history of substance abuse within the preceding 6 months prior to screening
• Have non-vertiginous dizziness (orthostatic or panic disorder) unless it could be clearly differentiated from Meniere'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
Active Comparator: Lamotrigine and Bupropion; Lamotrigine will be taken orally for a duration of 28 weeks, consisting of a six-week titration, 20-week study period, and two-week taper. Possible doses are 25mg one a day, 50mg once a day, 50mg twice a day, 75mg twice a day during titration; 125mg twice a day for the study period; and 125mg once a day during the two-week taper. Patients who discontinue at any point of the study will have a two-week taper of lamotrigine. Bupropion will be taken orally for the duration of 20 week at the dosage of 100mg twice a day.	Drug: Lamotrigine and Bupropion; Lamotrigine-oral pill taken once or twice a day with varying dosage per study timeline Bupropion-oral pill 100mg taken twice a day; Other Names: Lamictal; Wellbutrin XL; Forfivo XL; Wellbutrin SR; Lamictal XR; Lamictal ODT
Placebo Comparator: Placebo; The placebo will match the lamotrigine and bupropion dosage, frequency, and duration.	Drug: Placebo; Oral pill matched with lamotrigine to be taken once or twice a day per study timeline Oral pill matched with bupropion to be taken twice a day; Other Names: Microcrystalline cellulose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Ménière's vertigo attack frequency between groups	Number of Definitive Ménière's Vertigo attacks (DMVA), Number of Dizziness Days and overall dizziness severity during each 4-week of titration, and treatment compared to the 4-week lead-in phase. Vertigo ratings will be collected on a daily symptom diary throughout the study. DMVA is defined as vertigo for more than 20 minutes and corresponds to a vertigo rating of 3 or 4 on the daily symptom diary. A Dizziness Day is defined as vertigo rating of 1, 2, 3 or 4 on the daily symptom diary. Dizziness severity is the sum of all ratings (0-4) during each 4-week period.	Duration of lead-in to completion at week 30
Change in Ménière's vertigo attack frequency lamotrigine alone compared to lamotrigine and bupropion	Number of Definitive Ménière's Vertigo attacks (DMVA), Number of Dizziness Days and overall dizziness severity during each 4-week of treatment of lamotrigine alone and treatment of bupropion and lamotrigine.Vertigo ratings will be collected on a daily symptom diary throughout the study. DMVA is defined as vertigo for more than 20 minutes and corresponds to a vertigo rating of 3 or 4 on the daily symptom diary. A Dizziness Day is defined as vertigo rating of 1, 2, 3 or 4 on the daily symptom diary. Dizziness severity is the sum of all ratings (0-4) during each 4-week period.	Week 1 to Week 27

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in patients' self-assessment of dizziness	Between groups comparisons of Dizziness Handicap Inventory (DHI) at Week 27 compared to the baseline visit at the end of the lead-in phase. DHI at baseline compared to evaluation at end of treatment. Scores range from 0-100 with higher scores meaning more severe dizziness handicap	Baseline (Week 1) and Visit 8 (Week 27)
Changes in patients' self-assessment of overall affect of symptoms	Between groups comparisons of Ménière's Disease Patient-Oriented Symptom-Severity Index (MDPOSI) at Week 27 compared to the baseline visit at the end of the lead-in phase. MDPOSI at baseline compared to evaluation at end of treatment. Scores range from 0-80 with higher numbers indicating more frequent and severe symptoms.	Baseline (Week 1) and Visit 8 (Week 27)
Changes in patients' self-assessment of symptom impact on daily life function	Between groups comparisons of Ménière's Disease Self-Assessment (MDSA) at Week 27 compared to the baseline visit at the end of the lead-in phase. MDSA at baseline compared to evaluation at end of treatment. Scores range from 1-6 with higher numbers representing Ménière's Disease symptoms having a greater affect on the patient's ability to function in daily life.	Baseline (Week 1) and Visit 8 (Week 27)
Changes in patients' self-assessment of depression	Between groups comparisons of Patient Health Questionnaire-9 (PHQ-9) at Week 27 compared to the baseline visit at the end of the lead-in phase. PHQ-9 at baseline compared to evaluation at end of treatment. Scores range from 0-27 with higher numbers meaning more severe depression.	Baseline (Week 1) and Visit 8 (Week 27)
Changes in patients' self-assessment of anxiety	Between groups comparisons of General Anxiety Disorder-7 (GAD-7) at Week 27 compared to the baseline visit at the end of the lead-in phase. GAD-7 at baseline compared to evaluation at end of treatment. Scores range from 0-21 with higher numbers meaning more severe anxiety.	Baseline (Week 1) and Visit 8 (Week 27)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in patients' tinnitus from baseline to the end of treatment.	Between groups comparisons of Tinnitus Handicap Index (THI) at Week 27 compared to the baseline visit at the end of the lead-in phase. THI at baseline compared to evaluation at end of treatment. Score range from 0-100 with higher numbers representing a more severe tinnitus handicap.	Baseline (Week 1) and Visit 8 (Week 27)
Change in patients' hearing loss from baseline to the end of treatment.	Between groups comparisons of hearing loss at Week 24 compared to the baseline visit at the end of the lead-in phase. Hearing loss measured based off the pure-tone average at 500 Hz, 1000 Hz, 2000 Hz, and 3000 Hz measured in dB from audiometric report taken at Visit 1 and Visit 8.	Baseline (Week 1) and Visit 8 (Week 27)

Collaborators and Investigators

• Sponsor: Dent Neuroscience Research Center
• Collaborators: Cures Within Reach; Dent Family Foundation
• Investigators: Principal Investigator: Lixin Zhang, MD, PhD, Dent Neurologic Institute

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2020
• Primary Completion (Anticipated): July 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: May 26, 2022
• First Submitted That Met QC Criteria: June 14, 2022
• First Posted (Actual): June 15, 2022

Study Record Updates

• Last Update Posted (Actual): June 21, 2022
• Last Update Submitted That Met QC Criteria: June 17, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Bupropion; Lamotrigine; Dizziness; Meniere's Disease; Anticonvulsant; Lamictal; Wellbutrin; 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; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Cytochrome P-450 Enzyme Inhibitors; Anticonvulsants; Antidepressive Agents, Second-Generation; Sodium Channel Blockers; Cytochrome P-450 CYP2D6 Inhibitors; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Dopamine Uptake Inhibitors; Lamotrigine; Bupropion
• Other Study ID Numbers: DBTC-003

Drug and device information, study documents

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