Assessing the Efficacy of a Serotonin and Norepinephrine Reuptake Inhibitor for Improving Meniere's Disease Outcomes

As of yet, the cause of Meniere's disease is uncertain and there is no cure. Given the lack of high level evidence for treatments, we seek to perform a randomized, placebo-controlled, double-blind, crossover, pilot trial of venlafaxine for treating Meniere's disease. Venlafaxine is a safe and well-tolerated medication. It has never been trialed in Meniere's disease, but there is evidence that it could be effective in helping with vertigo attacks and other aspects of the disorder.

Study Overview

• Status: Completed
• Conditions: Meniere Disease
• Intervention / Treatment: Drug: Venlafaxine; Drug: Placebo oral tablet

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Habib Rizk, MD; Phone Number: 843-876-0112; Email: rizkh@musc.edu
• Study Contact Backup: Name: Yuan Liu, MD; Phone Number: 843-834-5077; Email: liuyua@musc.edu

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical Univeristy of South Carolina

Participation Criteria

Eligibility Criteria

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

Description

Study subjects will be prospectively recruited from the population of patients presenting with dizziness to our tertiary, multidisciplinary, vestibular-focused, neurotology clinic. Subjects must meet the following inclusion criteria:

• be 18 years of age or older;
• have definite MD as defined by the Barany Society 2015 international consensus statement;
• have active MD with at least 2 vertigo episodes in the month prior to enrollment; and score at least 36 on the Dizziness Handicap Inventory (DHI), representing at least moderate handicap.

Patients with the following will be excluded:

• other concurrent vestibular or balance disorder (especially those with vestibular migraine-related vertigo episodes despite not meeting diagnostic criteria for vestibular migraine);
• currently taking venlafaxine, SSRIs, or SNRIs;
• history of medical (e.g. gentamicin) or surgical (e.g. labyrinthectomy) vestibular ablative treatment;
• history of otologic, lateral skull base, or brain surgery;
• history of radiation to the head or neck;
• known neurologic disorder affecting cognition;
• currently taking another serotonin modulating medication;
• seizures;
• stroke;
• myocardial infarction;
• hepatic or renal impairment;
• hyperlipidemia;
• coagulopathy;
• psychiatric disorder other than anxiety or depression;
• glaucoma;
• uncontrolled hypertension;
• pregnancy or intention of pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo oral tablet; Daily oral intake
Experimental: Venlafaxine Arm	Drug: Venlafaxine; Daily oral intake 37.5 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Score on Dizziness Handicap Inventory (DHI)	The Dizziness Handicap Inventory is a 25-item questionnaire of self-perceived handicap from dizziness.There are 7 questions in the physical domain, 9 in the emotional domain, and 8 in the functional domain. It is scored from 0 (no perceived disability) to 100 (maximum perceived disability).	Baseline to end of treatment (6 months)
Change in Score on Neuropsychological Vertigo Inventory (NVI)	The English version of the Neuropsychological Vertigo Inventory consists of 28-items with a 5-point Likert scale for each question. It is a cognitive assessment specific to patients with dizziness. The NVI assesses 7 domains of cognition: space perception, attention, time perception, memory, emotional, visual/ocular and motor. The score ranges from 0 to 140. The higher the score on the NVI the worse the cognitive function of the subject.	Baseline to end of treatment (6 months)
Change in Score on Cognitive Failure Questionnaire (CFQ)	The Cognitive Failure Questionnaire is a 25-item survey which assesses cognitive and executive function not tied to any specific disease state. It aims to assess perception, memory, and motor function in everyday tasks.The score ranges from 0 to 100 The higher score on the CFQ, the more frequent the cognitive failures experienced by the subject	Baseline to end of treatment (6 months)
Change in Score on Patient Health Questionnaire (PHQ9)	The Patient Health Questionnaire is a 9-item survey which assesses the severity of depression. A low score is indicative of little to no depressive symptoms, and a high score is indicative of Moderately severe to severe depressive symptoms. Scores range from 0 to 27 with scores higher than 20 indicative of significant risk for depression and scores below 10 indicative at most of a mild depression.	Baseline to end of treatment (6 months)
Change in Score on Penn State Worry Questionnaire (PSWQ)	The PSWQ is a 16-item survey for assessment of anxiety which has been used to identify generalized anxiety disorder. Scores range from 16 (Low worry) to 80 (high worry). A score higher than 60 is indicative of significant anxiety and risk for an anxiety disorder	Baseline to end of treatment (6 months)
Change in Score on The Meniere's Disease Patient-Oriented Symptom Index (MDPOSI)	The Meniere's Disease Patient-Oriented Symptom Index is a 23-item survey developed as a MD-specific tool to assess the impact of MD symptoms on patients' lives. The score ranges from 0 to 100 with the higher score indicating an active disease with significant impact on function and quality of life.	Baseline to end of treatment (6 months)
Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey	The Medical Outcomes Study 20-item Short Form Health Survey is a 20-item general health questionnaire to assess quality of life in chronic diseases. It assesses 6 areas of health: physical functioning, role functioning, social functioning, mental health, health perceptions, and pain. Scores range between 0 and 100, with 100 indicating best possible function and 0 the worst possible function	Baseline to end of treatment (6 months)
Number of Vertigo Episodes	Patients will be keeping a diary throughout the study period and beyond.	6 months
Severity of Vertigo	The study team will use a modified version of vertigo control classification because the treatment phases are 2 months long and the study team will not be able to wait 18-24 months after treatment to assess efficacy per academy guidelines. Previous studies have defined four categories of response to treatment: 1) very good response if more than 75% reduction in vertigo spells frequency and/or intensity, 2) good response if 50-75% reduction, 3) fair response if 25-50% reduction, and 4) poor response if less than 25% reduction. The vertigo classes will be defined as follows; Class A: 0 (complete control of vertigo) Class B: 0-40 or >60% reduction in mean vertigo episode severity (good control of vertigo) Class C: 41-80 or 20-60% reduction in severity (fair control of vertigo) Class D: 81-120 or -20-20% reduction in severity (no change in vertigo) Class E: >120 or >20% worsening in severity (worse vertigo)	6 months

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: American Hearing Research Foundation; Cures within Reach Foundation
• Investigators: Principal Investigator: Habib Rizk, MD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2020
• Primary Completion (Actual): September 13, 2023
• Study Completion (Actual): September 14, 2023

Study Registration Dates

• First Submitted: December 30, 2019
• First Submitted That Met QC Criteria: January 2, 2020
• First Posted (Actual): January 6, 2020

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Otorhinolaryngologic Diseases; Labyrinth Diseases; Ear Diseases; Endolymphatic Hydrops; Meniere Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride
• Other Study ID Numbers: 00091200

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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