Meniere Disease
Conditions
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.
Interventions
DRUGVenlafaxine
Daily oral intake 37.5 mg
DRUGPlacebo oral tablet
Daily oral intake
Sponsors
American Hearing Research Foundation
Cures Within Reach
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Vertigo Episodes | 6 months | Patients will be keeping a diary throughout the study period and beyond. |
| Severity of Vertigo | 6 months | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Score on Penn State Worry Questionnaire (PSWQ) | Baseline to end of treatment (6 months) | 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 |
| Change in Score on Patient Health Questionnaire (PHQ9) | Baseline to end of treatment (6 months) | 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. |
| Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Baseline to end of treatment (6 months) | 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. Each score ranges between 0 and 100, with 100 indicating best possible function and 0 the worst possible function. |
| Change in Score on Neuropsychological Vertigo Inventory (NVI) | Baseline to end of treatment (6 months) | 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. |
| Change in Score on Dizziness Handicap Inventory (DHI) | Baseline to end of treatment (6 months) | 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). |
| Change in Score on Cognitive Failure Questionnaire (CFQ) | Baseline to end of treatment (6 months) | 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 |
| Change in Score on The Meniere's Disease Patient-Oriented Symptom Index (MDPOSI) | Baseline to end of treatment (6 months) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Venlafaxine, Then Placebo Venlafaxine 37.5mg tablet by mouth once daily in first 8 week period and placebo tablet by mouth once daily in the second 8 week period. | 20 |
| Placebo, Then Venlafaxine Placebo tablet by mouth once daily in first 8 week period and venlafaxine 37.5mg tablet by mouth once daily in the second 8 week period. | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Venlafaxine, Then Placebo | Total | Placebo, Then Venlafaxine |
|---|---|---|---|
| Age, Continuous | 54.9 years STANDARD_DEVIATION 17.2 | 56.6 years STANDARD_DEVIATION 14.3 | 58.3 years STANDARD_DEVIATION 11 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 32 Participants | 15 Participants |
| Region of Enrollment United States | 20 participants | 40 participants | 20 participants |
| Sex: Female, Male Female | 9 Participants | 18 Participants | 9 Participants |
| Sex: Female, Male Male | 11 Participants | 22 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 |
| other Total, other adverse events | 6 / 40 | 3 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 |
Outcome results
Primary
Number of Vertigo Episodes
Patients will be keeping a diary throughout the study period and beyond.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Venlafaxine Arm | Number of Vertigo Episodes | 5.41 number of episodes | Standard Deviation 4.44 |
| Placebo Arm | Number of Vertigo Episodes | 5.03 number of episodes | Standard Deviation 4.57 |
| Baseline Score | Number of Vertigo Episodes | 13.78 number of episodes | Standard Deviation 10.05 |
p-value: <0.05ANOVA
p-value: <0.05ANOVA
p-value: >0.05ANOVA
p-value: <0.001ANOVA
Primary
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)
Time frame: 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Venlafaxine Arm | Severity of Vertigo | Class B Control | 38 Percentage of members in arm |
| Venlafaxine Arm | Severity of Vertigo | Class D Control | 5 Percentage of members in arm |
| Venlafaxine Arm | Severity of Vertigo | Class C Control | 30 Percentage of members in arm |
| Venlafaxine Arm | Severity of Vertigo | Class E Control | 11 Percentage of members in arm |
| Venlafaxine Arm | Severity of Vertigo | Class A Control | 16 Percentage of members in arm |
| Placebo Arm | Severity of Vertigo | Class E Control | 9 Percentage of members in arm |
| Placebo Arm | Severity of Vertigo | Class A Control | 24 Percentage of members in arm |
| Placebo Arm | Severity of Vertigo | Class B Control | 32 Percentage of members in arm |
| Placebo Arm | Severity of Vertigo | Class C Control | 32 Percentage of members in arm |
| Placebo Arm | Severity of Vertigo | Class D Control | 3 Percentage of members in arm |
Secondary
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
Time frame: Baseline to end of treatment (6 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Venlafaxine Arm | Change in Score on Cognitive Failure Questionnaire (CFQ) | 33.92 score on a scale | Standard Deviation 16.35 |
| Placebo Arm | Change in Score on Cognitive Failure Questionnaire (CFQ) | 36.4 score on a scale | Standard Deviation 17.63 |
| Baseline Score | Change in Score on Cognitive Failure Questionnaire (CFQ) | 36.14 score on a scale | Standard Deviation 18.18 |
p-value: =0.8ANOVA
Secondary
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).
Time frame: Baseline to end of treatment (6 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Venlafaxine Arm | Change in Score on Dizziness Handicap Inventory (DHI) | 45.46 score on a scale | Standard Deviation 24.2 |
| Placebo Arm | Change in Score on Dizziness Handicap Inventory (DHI) | 45.2 score on a scale | Standard Deviation 20.77 |
| Baseline Score | Change in Score on Dizziness Handicap Inventory (DHI) | 55.62 score on a scale | Standard Deviation 16.73 |
p-value: =0.054ANOVA
Secondary
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.
Time frame: Baseline to end of treatment (6 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Venlafaxine Arm | Change in Score on Neuropsychological Vertigo Inventory (NVI) | 59.41 score on a scale | Standard Deviation 18.67 |
| Placebo Arm | Change in Score on Neuropsychological Vertigo Inventory (NVI) | 63.31 score on a scale | Standard Deviation 17.78 |
| Baseline Score | Change in Score on Neuropsychological Vertigo Inventory (NVI) | 65.11 score on a scale | Standard Deviation 20.01 |
p-value: =0.425ANOVA
Secondary
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.
Time frame: Baseline to end of treatment (6 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Venlafaxine Arm | Change in Score on Patient Health Questionnaire (PHQ9) | 5.49 score on a scale | Standard Deviation 5.27 |
| Placebo Arm | Change in Score on Patient Health Questionnaire (PHQ9) | 7.17 score on a scale | Standard Deviation 5.73 |
| Baseline Score | Change in Score on Patient Health Questionnaire (PHQ9) | 7.43 score on a scale | Standard Deviation 5.32 |
p-value: =0.167ANOVA
Secondary
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
Time frame: Baseline to end of treatment (6 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Venlafaxine Arm | Change in Score on Penn State Worry Questionnaire (PSWQ) | 44.35 score on a scale | Standard Deviation 14.36 |
| Placebo Arm | Change in Score on Penn State Worry Questionnaire (PSWQ) | 45.63 score on a scale | Standard Deviation 13.48 |
| Baseline Score | Change in Score on Penn State Worry Questionnaire (PSWQ) | 47.16 score on a scale | Standard Deviation 14.11 |
p-value: =0.686ANOVA
Secondary
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. Each score ranges between 0 and 100, with 100 indicating best possible function and 0 the worst possible function.
Time frame: Baseline to end of treatment (6 months)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Venlafaxine Arm | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Physical Functioning | 14.92 score on a scale | Standard Deviation 3.34 |
| Venlafaxine Arm | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Role Functioning | 4.62 score on a scale | Standard Deviation 1.62 |
| Venlafaxine Arm | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Mental Health | 22.24 score on a scale | Standard Deviation 6.79 |
| Venlafaxine Arm | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Social Functioning | 4.38 score on a scale | Standard Deviation 1.67 |
| Venlafaxine Arm | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Health Perceptions | 16.95 score on a scale | Standard Deviation 4.91 |
| Venlafaxine Arm | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Pain | 2.6 score on a scale | Standard Deviation 1.44 |
| Placebo Arm | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Pain | 2.74 score on a scale | Standard Deviation 1.42 |
| Placebo Arm | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Physical Functioning | 14.54 score on a scale | Standard Deviation 3.42 |
| Placebo Arm | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Social Functioning | 4.54 score on a scale | Standard Deviation 1.44 |
| Placebo Arm | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Health Perceptions | 16.17 score on a scale | Standard Deviation 5.46 |
| Placebo Arm | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Role Functioning | 4.6 score on a scale | Standard Deviation 1.61 |
| Placebo Arm | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Mental Health | 22 score on a scale | Standard Deviation 5.95 |
| Baseline Score | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Role Functioning | 4.38 score on a scale | Standard Deviation 1.52 |
| Baseline Score | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Mental Health | 20.95 score on a scale | Standard Deviation 6.06 |
| Baseline Score | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Pain | 2.76 score on a scale | Standard Deviation 1.52 |
| Baseline Score | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Social Functioning | 3.84 score on a scale | Standard Deviation 1.44 |
| Baseline Score | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Physical Functioning | 13.81 score on a scale | Standard Deviation 3.6 |
| Baseline Score | Change in Score on The Medical Outcomes Study 20-item Short Form Health Survey | Health Perceptions | 15.07 score on a scale | Standard Deviation 5.1 |
Comparison: SF20 Physical Functioningp-value: =0.31ANOVA
Comparison: SF20 Role Functioningp-value: 0.633ANOVA
Comparison: SF20 Mental Healthp-value: 0.424ANOVA
Comparison: SF20 Social Functioningp-value: 0.057ANOVA
Comparison: SF20 Health Perceptionsp-value: 0.296ANOVA
Comparison: SF20 Painp-value: 0.872ANOVA
Secondary
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.
Time frame: Baseline to end of treatment (6 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Venlafaxine Arm | Change in Score on The Meniere's Disease Patient-Oriented Symptom Index (MDPOSI) | 46.81 score on a scale | Standard Deviation 15.59 |
| Placebo Arm | Change in Score on The Meniere's Disease Patient-Oriented Symptom Index (MDPOSI) | 46.31 score on a scale | Standard Deviation 16.32 |
| Baseline Score | Change in Score on The Meniere's Disease Patient-Oriented Symptom Index (MDPOSI) | 50.68 score on a scale | Standard Deviation 13.66 |
p-value: =0.538ANOVA