Meniere's Disease, Ménière's Vertigo, Vertigo, Aural, Vertigo, Intermittent
Conditions
Keywords
Lamotrigine, Lamictal, Anticonvulsant, Ménière's disease, Vertigo attack, Dizziness, Vestibular disorder
Brief summary
This double-blinded study evaluates the frequency of vertigo attacks and the quality of life of patients diagnosed with Ménière's disease after being randomly assigned to take a placebo or lamotrigine.
Interventions
DRUGLamotrigine
Lamotrigine will be taken orally on a daily basis for the duration of 20 weeks, consisting of a six-week titration, 12-week study period, and two-week taper. Possible doses for patients are 25mg twice a day, 50mg twice a day, and 100 mg twice a day during titration; 150mg twice a day for the 12-week study period; 150mg once a day for Week 1 of the taper; and 75mg once a day for Week 2 of the taper. Each increase in dose will be maintained for two weeks before deciding to further increase or decrease based on tolerability. Patients who discontinue at any point of the study will have a two-week taper consisting of the current dose once a day for one week followed by half the dose once a day for another week.
DRUGPlacebo
The placebo will match the lamotrigine dosage, frequency and duration.
Sponsors
University at Buffalo
Dent Neuroscience Research Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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
* Male and female participants aged 18 years or older * Diagnosed with unilateral definite Ménière's disease according to the AAO-HNS 1995 criteria, confirmed by an ENT * Active vertigo: at least two Ménière's vertigo attacks (defined as lasting 20 minutes or longer and associated with tinnitus, ear fullness, or low frequency hearing loss and nausea/vomiting) every four weeks during the eight-week qualification period and at least two more Ménière's vertigo attacks during the lead-in phase prior to randomization * Documented unilateral lower frequency hearing loss defined as the four-tone average (arithmetic mean rounded to the nearest whole number) of the pure-tone thresholds at 0.25, 0.5, 1 and 2 kilohertz (kHz) more than or equal to 25 decibels (dB) of the worse audiogram during the six months before screening * Have tried diuretics for at least one month and discontinued treatment due to continued vertigo attacks * All other co-existing medical or psychiatric conditions are stable, and no greater than moderate severity * Willing to avoid pregnancy during the entirety of the study (abstinence or two forms of acceptable birth control, such as condoms and oral contraceptives)
Exclusion criteria
* Bilateral Ménière's disease * Current or past history of migraine * Any other neuro-otologic disease or major vestibular abnormality found during screening that could confound the evaluation of Ménière's symptoms * Previous intolerance or sensitivity to lamotrigine * On any prohibited medication within four weeks prior to the study * History of tympanostomy tubes with evidence of perforation or lack of closure * IT gentamicin injections or endolymphatic sac surgery within the last year * History of or current immunodeficiency disease, nephrolithiasis, hypertension, cardiac disease, arrhythmia, hypercholesterolemia, hemiplegic/basilar migraine, stroke, diabetes, vascular disease or kidney disease * Family history of unexplained deafness * Pregnant or breastfeeding * Current diseases or conditions that may be associated with an altered perception of processing stimuli * Current severe medical condition(s) that in the view of the investigator prohibits participation * Previously used the investigational drug * Current non-vertiginous dizziness (orthostatic or panic disorder) unless it could be clearly differentiated from Ménière's attacks by the participant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Ménière's Vertigo Attack Frequency Between Lamotrigine and Placebo Group | Duration of 12-week pre-treatment and 12-week study period (treatment) | Measured with a daily questionnaire |
| Change in Ménière's Vertigo Attack Frequency Within Lamotrigine Group | Duration of 12-week pre-treatment and 12-week study period (treatment) | Measured with daily questionnaire |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Ménière's Vertigo Attacks in Three-Week Intervals Between Lamotrigine and Placebo Groups | Duration of Week 16 to 18 | Measured with a daily questionnaire. |
| Improvement in Pure Tone Average in the Affected Ear | Prior to randomization and at completion of 12-week study period | Measured using the average of 500, 1000, 2000, and 3000 Hz presentation level (dB) |
| Improvement in Symptoms Severity | 12-week pre-treatment period; 6 week titration; 12-week study period (treatment) | Based of rating on Clinical Global Impression of Change (CGI) score of blinded physician |
| DHI Scores | Baseline (Week 1) and end of study (Week 18) | Dizziness Handicap Inventory (DHI). Minimum score=0. Maximum score=100. Higher scores mean a worse outcome. |
Countries
United States
Participant flow
Pre-assignment details
12-week pre-treatment period
Participants by arm
| Arm | Count |
|---|---|
| Placebo The placebo will match the lamotrigine dosage, frequency and duration. | 8 |
| Lamotrigine Lamotrigine will be taken orally for the duration of 20 weeks, consisting of a six-week titration, 12-week study period, and two-week taper. Possible doses are 25mg twice a day, 50mg twice a day, and 100 mg twice a day during titration; 150mg twice a day for the 12-week study period; 150mg once a day for Week 1 of the taper; and 75mg once a day for Week 2 of the taper. Patients who withdraw at any point of the study will have a two-week taper consisting of the current dose once a day for one week followed by half the dose once a day for another week. | 7 |
| Total | 15 |
Baseline characteristics
| Characteristic | Placebo | Total | Lamotrigine |
|---|---|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 13.8 | 57.6 years STANDARD_DEVIATION 13.1 | 55.1 years STANDARD_DEVIATION 12.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 14 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 14 Participants | 7 Participants |
| Region of Enrollment United States | 8 participants | 15 participants | 7 participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 7 |
| other Total, other adverse events | 1 / 8 | 0 / 7 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 |
Outcome results
Primary
Change in Ménière's Vertigo Attack Frequency Between Lamotrigine and Placebo Group
Measured with a daily questionnaire
Time frame: Duration of 12-week pre-treatment and 12-week study period (treatment)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Ménière's Vertigo Attack Frequency Between Lamotrigine and Placebo Group | Pre-Treatment (Week -12 to -1) | 18.88 Average Total Number of Vertigo Attacks | Standard Deviation 6.27 |
| Placebo | Change in Ménière's Vertigo Attack Frequency Between Lamotrigine and Placebo Group | Treatment (Week 7 to 18) | 13.50 Average Total Number of Vertigo Attacks | Standard Deviation 14.54 |
| Lamotrigine | Change in Ménière's Vertigo Attack Frequency Between Lamotrigine and Placebo Group | Pre-Treatment (Week -12 to -1) | 18.00 Average Total Number of Vertigo Attacks | Standard Deviation 12.65 |
| Lamotrigine | Change in Ménière's Vertigo Attack Frequency Between Lamotrigine and Placebo Group | Treatment (Week 7 to 18) | 4.57 Average Total Number of Vertigo Attacks | Standard Deviation 4.96 |
Comparison: Null hypothesis: no difference between groups in average total number of vertigo attacksp-value: 0.561895% CI: [-3.49, 21.35]Wilcoxon (Mann-Whitney)
Primary
Change in Ménière's Vertigo Attack Frequency Within Lamotrigine Group
Measured with daily questionnaire
Time frame: Duration of 12-week pre-treatment and 12-week study period (treatment)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Ménière's Vertigo Attack Frequency Within Lamotrigine Group | Pre-treatment | 18.00 Average Total Number of Vertigo Attacks | Standard Deviation 12.65 |
| Placebo | Change in Ménière's Vertigo Attack Frequency Within Lamotrigine Group | Study Period | 4.57 Average Total Number of Vertigo Attacks | Standard Deviation 4.96 |
Comparison: Null hypothesis: no difference between average total number of vertigo attacks in pre-treatment and treatmentp-value: 0.03429Wilcoxon (Mann-Whitney)
Secondary
DHI Scores
Dizziness Handicap Inventory (DHI). Minimum score=0. Maximum score=100. Higher scores mean a worse outcome.
Time frame: Baseline (Week 1) and end of study (Week 18)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | DHI Scores | Baseline | 57.50 score on DHI | Standard Deviation 17.26 |
| Placebo | DHI Scores | End of Study | 49.43 score on DHI | Standard Deviation 25.73 |
| Lamotrigine | DHI Scores | Baseline | 37.14 score on DHI | Standard Deviation 12.05 |
| Lamotrigine | DHI Scores | End of Study | 38.29 score on DHI | Standard Deviation 19.44 |
p-value: 0.038595% CI: [-15.64, 37.92]Wilcoxon (Mann-Whitney)
Secondary
Difference in Ménière's Vertigo Attacks in Three-Week Intervals Between Lamotrigine and Placebo Groups
Measured with a daily questionnaire.
Time frame: Duration of Week 16 to 18
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Difference in Ménière's Vertigo Attacks in Three-Week Intervals Between Lamotrigine and Placebo Groups | 4.86 Average Total Number of Vertigo Attacks | Standard Deviation 4.02 |
| Lamotrigine | Difference in Ménière's Vertigo Attacks in Three-Week Intervals Between Lamotrigine and Placebo Groups | 0.29 Average Total Number of Vertigo Attacks | Standard Deviation 0.76 |
Comparison: Null hypothesis: no difference in total average number of vertigo attacks during 3 week time periodsp-value: 0.009295% CI: [0.85, 8.29]Wilcoxon (Mann-Whitney)
Secondary
Improvement in Pure Tone Average in the Affected Ear
Measured using the average of 500, 1000, 2000, and 3000 Hz presentation level (dB)
Time frame: Prior to randomization and at completion of 12-week study period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Improvement in Pure Tone Average in the Affected Ear | 3 Participants |
| Lamotrigine | Improvement in Pure Tone Average in the Affected Ear | 5 Participants |
Secondary
Improvement in Symptoms Severity
Based of rating on Clinical Global Impression of Change (CGI) score of blinded physician
Time frame: 12-week pre-treatment period; 6 week titration; 12-week study period (treatment)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Improvement in Symptoms Severity | 3 Participants |
| Lamotrigine | Improvement in Symptoms Severity | 6 Participants |