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

NCT04218123 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 00091200
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Meniere Disease

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (7)

• Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey

  Baseline to end of treatment (6 months)

• Change in Score on The Meniere's Disease Patient-Oriented Symptom Index (MDPOSI)

  Baseline to end of treatment (6 months)

• Change in Score on Penn State Worry Questionnaire (PSWQ)

  Baseline to end of treatment (6 months)

• Change in Score on Patient Health Questionnaire (PHQ9)

  Baseline to end of treatment (6 months)

• Change in Score on Cognitive Failure Questionnaire (CFQ)

  Baseline to end of treatment (6 months)

Study Arms (2)

Venlafaxine Arm

EXPERIMENTAL

Drug: Venlafaxine

Placebo

PLACEBO COMPARATOR

Drug: Placebo oral tablet

Interventions

Venlafaxine DRUG

Daily oral intake 37.5 mg

Venlafaxine Arm

Placebo oral tablet DRUG

Daily oral intake

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

Sponsors & Collaborators

• Medical University of South Carolina: lead
• American Hearing Research Foundation: collaborator
• Cures Within Reach: collaborator

Study Sites (1)

Medical Univeristy of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

• Rizk H, Monaghan NP, Shah S, Liu Y, Keith BA, Jeong S, Nguyen SA. Efficacy of a Serotonin-Norepinephrine Reuptake Inhibitor as a Treatment for Meniere Disease: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2024 Nov 1;150(11):935-942. doi: 10.1001/jamaoto.2024.2241.

  PMID: 39235772 DERIVED

MeSH Terms

Conditions

Meniere Disease

Interventions

Venlafaxine Hydrochloride

Condition Hierarchy (Ancestors)

Endolymphatic Hydrops; Labyrinth Diseases; Ear Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Phenethylamines; Ethylamines; Amines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Lipids

Limitations and Caveats

This study was designed in 2019 with a power analysis that estimated a 20% placebo response in Meniere's Disease. This was a gross underestimation in hindsight. A systematic review with meta-analysis published in 2023 has illustrated that this effect is much stronger, closer to 50% in patients with Meniere's Disease, which may affect the ability to detect symptomatic differences between venlafaxine and placebo treatment periods, respectively.

Results Point of Contact

• Title: Habib Rizk, MD, MSc
• Organization: Department of Otolaryngology - Head and Neck Surgery, Medical University of South Carolina

rizkh@musc.edu

8438760112

Study Officials

• Habib Rizk, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 30, 2019
• First Posted: January 6, 2020
• Study Start: February 5, 2020
• Primary Completion: September 13, 2023
• Study Completion: September 14, 2023
• Last Updated: July 23, 2024
• Results First Posted: June 24, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)