Treatment of Meniere's Disease With Migraine Medications

Treatment of Meniere's Disease With Nortriptyline-Topiramate Stepwise Regimen: A Randomized Double-Blinded Clinical Trial

Meniere's disease (MD) is a chronic disease with a variety of fluctuating signs and symptoms, which include vertigo, hearing loss, tinnitus (ringing noise in the ear), aural pressure (feeling of ear fullness), and disequilibrium (lack of stability). Vertigo represents one of the most common and distressing problems in MD patients, and it causes various somatic and psychological disorders that interfere with the patient's quality of life. Despite the large economic and emotional impact of symptoms in MD patients, there is no FDA-approved medication to treat this debilitating condition. As such, our objective in this study is to evaluate the therapeutic potential of novel medications in treating MD that have previously shown astonishing promise in our clinical practice.

Study Overview

• Status: Recruiting
• Conditions: Ménière
• Intervention / Treatment: Drug: nortriptyline + topiramate

Detailed Description

This study is 8 weeks in duration. There are two arms in the experiment: the first is nortriptyline (7.5 mg) plus topiramate (10 mg), the second is hydrochlorothiazide (25 mg) plus triamterene (37.5 mg) with placebo being added in case of a dosage increase. This is a double-blinded trial. Participants will be randomized to one arm for the duration of the trial using simple randomization with a computer-generated number. Both groups may receive dosage increases weekly if symptoms do not improve. Symptomatic survey scores from each arm will be obtained before and after treatment and weekly. An unblinded clinical researcher will also become involved with patients' treatments as they start to report changes in symptoms in order to monitor their safety and provide advice on change in dosage if patients have questions.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hamid R Djalilian; Phone Number: (800) 263-9547; Email: hdjalili@hs.uci.edu
• Study Contact Backup: Name: Mehdi Abouzari; Phone Number: (714) 509-6096; Email: mabouzar@hs.uci.edu

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • University of California, Irvine Medical Center ENT Clinic (Pavilion 2)
      • Contact: Hamid R Djalilian, MD; Phone Number: 800-263-9547; Email: hdjalili@hs.uci.edu
      • Contact: Mehdi Abouzari, MD, PhD; Phone Number: 714-509-6096; Email: mabouzar@hs.uci.edu
      • Principal Investigator: Hamid R Djalilian, MD
      • Sub-Investigator: Mehdi Abouzari, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with active or frequent Meniere's Disease.
2. Male or female between the ages of 25 to 85 years.
3. Subject must be compliant with the medication and attend study visits.
4. Must be able to read and write in the English language to provide consenting.

Exclusion Criteria:

1. Pregnancy will result in automatic exclusion from the study. A urine pregnancy test to rule out pregnancy for all women who are of childbearing potential.
2. Subjects with history of surgery for Meniere's Disease.
3. Subject with history of an adverse reaction to medication being prescribed.
4. Subject suffers from a medical condition or has history that may be concerning to the investigator's clinical opinion.
5. Subjects with psychosis.
6. Subjects with neurological neoplasm.
7. All contraindications for the medications which prevent subjects from randomization will be considered as exclusion criteria.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nortriptyline + topiramate; Nortriptyline (starting dose 7.5 mg) plus Topiramate (starting dose 10 mg) with appropriate dosage increase as necessary	Drug: nortriptyline + topiramate; nortriptyline (7.5mg) + topiramate (10mg) taken 1x per day and escalate weekly as needed for 8 weeks
Active Comparator: hydrochlorothiazide + triamterene + placebo; hydrochlorothiazide (starting dose 25 mg) plus triamterene (starting dose 37.5 mg) with placebo being added in case of a dosage increase	Drug: nortriptyline + topiramate; nortriptyline (7.5mg) + topiramate (10mg) taken 1x per day and escalate weekly as needed for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective improvement of Meniere's Disease	The primary outcome variable is derived from the validated Meniere's Disease Outcome Questionnaire (MDOQ) with 18 multiple-choice questions to compare quality of life before and after treatment. The question multiple choices are rated on a scale from 0 to 4 where the higher score indicates the higher quality of life. For each patient, the sum of his/her answers is divided (and x100) by the maximum possible scores for the pre-treatment questions and the post-treatment questions, separately. The outcome measure is the absolute change from pre- to post-treatment scores. Two-sample t test will be used to compare the outcome variable between the two treatment groups.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tinnitus Functional Index (TFI)	Subjective improvement from baseline in tinnitus symptoms as measured by Tinnitus Functional Index (TFI). The TFI is scored from 0% to 100%, with higher scores indicating a more negative impact of tinnitus.	8 weeks
Patient Health Questionnaire (PHQ)	Subjective improvement in depression symptoms based on patient health questionnaire (PHQ). The PHQ is scored from 0 to 27, with a higher score indicating increased depression severity.	8 weeks
Perceived Stress Scale (PSS)	Subjective improvement in stress based on perceived stress scale (PSS). The PSS is scored from 0 to 40, with higher scores indicating higher perceived stress.	8 weeks
Sleep Quality Index (SQI)	Subjective improvement in sleep quality based on sleep quality index (SQI). The SQI is scored from 0 to 21, with higher scores indicating worse quality of sleep.	8 weeks
Visual analog scale (VAS)	Subjective improvement in tinnitus loudness severity based on a visual analog scale (VAS). The VAS is scored from 0 to 10, with a higher score representing an increased severity of tinnitus.	8 weeks
Dizziness handicap index (DHI)	Subjective improvement in dizziness handicap index (DHI). There is a maximum score of 100 (28 points for physical, 36 points for emotional and 36 points for functional) and a minimum score of 0. The higher the score, the greater the perceived handicap due to dizziness.	8 weeks
Meniere's Disease Outcomes Questionnaire (MDOQ)	Subjective improvement in Meniere's Disease Outcomes Questionnaire (MDOQ). To measure the quality of life in patients with Ménière's disease and to assess quality-of-life outcomes.	8 weeks

Collaborators and Investigators

• Sponsor: University of California, Irvine

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Anticipated): August 1, 2024
• Study Completion (Anticipated): August 1, 2024

Study Registration Dates

• First Submitted: October 7, 2021
• First Submitted That Met QC Criteria: October 12, 2022
• First Posted (Actual): October 17, 2022

Study Record Updates

• Last Update Posted (Actual): October 17, 2022
• Last Update Submitted That Met QC Criteria: October 12, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Meniere's Disease, medication, randomized, trial, migraine
• Additional Relevant MeSH Terms: Otorhinolaryngologic Diseases; Labyrinth Diseases; Ear Diseases; Endolymphatic Hydrops; Meniere Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Anticonvulsants; Antidepressive Agents, Tricyclic; Adrenergic Uptake Inhibitors; Nortriptyline; Topiramate
• Other Study ID Numbers: 2021-6445

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