A Two-Year Randomized Trial of Interventions to Decrease Stress Hormone Vasopressin Production in Patients with Meniere's Disease-A Pilot Study

Abstract

Meniere's disease, a common inner ear condition, has an incidence of 15-50 per 100,000. Because mental/physical stress and subsequent increase in the stress hormone vasopressin supposedly trigger Meniere's disease, we set a pilot study to seek new therapeutic interventions, namely management of vasopressin secretion, to treat this disease. We enrolled 297 definite Meniere's patients from 2010 to 2012 in a randomized-controlled and open-label trial, assigning Group-I (control) traditional oral medication, Group-II abundant water intake, Group-III tympanic ventilation tubes and Group-IV sleeping in darkness. Two hundred sixty-three patients completed the planned 2-year-follow-up, which included assessment of vertigo, hearing, plasma vasopressin concentrations and changes in stress/psychological factors. At 2 years, vertigo was completely controlled in 54.3% of patients in Group-I, 81.4% in Group-II, 84.1% in Group-III, and 80.0% in Group-IV (statistically I < II = III = IV). Hearing was improved in 7.1% of patients in Group-I, 35.7% in Group-II, 34.9% in Group-III, and 31.7% in Group-IV (statistically I < II = III = IV). Plasma vasopressin concentrations decreased more in Groups-II, -III, and -IV than in Groups-I (statistically I < II = III = IV), although patients' stress/psychological factors had not changed. Physicians have focused on stress management for Meniere's disease. However, avoidance of stress is unrealistic for patients who live in demanding social environments. Our findings in this pilot study suggest that interventions to decrease vasopressin secretion by abundant water intake, tympanic ventilation tubes and sleeping in darkness is feasible in treating Meniere's disease, even though these therapies did not alter reported mental/physical stress levels.

Trial registration: ClinicalTrials.gov NCT01099046.

Fig 1. Flow chart of the present randomized controlled study.

Fig 2. Vertigo attacks in patients with definite Meniere's disease 18–24 months into study.

Ratios of the number of cases with “no vertigo” and “others”18–24 months after treatment are shown in each group. “No vertigo” means an absence of vertigo attacks from 18–24 months; “others” means better, worse and no change (as defined in Patients and Methods) during the same period. *: statistically significant. Percentages mean ratios of the number of these patients.

Fig 3. Two-year follow-up hearing in patients with definite Meniere's disease.

Ratios of the number of cases with “better hearing”, “no change of hearing” and “worse hearing”18–24 months after treatment are shown in each group. “Better”, ≥10 dB difference between pre- and post-treatment hearing levels; “worse”, ≤−10 dB difference; “no change”, other. *: statistically significant. Percentages mean ratios of the number of these patients.

Fig 4. Pre-and post-treatment stress and psychological assessment in patients with definite Meniere's disease.

In all four panels, averaged levels or points were compared between pre- and post-treatments in each group. Panel A: In comparison with G-I, plasma vasopressin concentrations (pAVP: pg/mL) were significantly reduced in G-II, G-III and G-IV. Panel B: Serum cortisol concentrations (crtsl: μg/mL) did not change. Panel C: Self-rating depression scale scores (SDS: points) did not change. Panel D: Stress response scale scores (SRS-18: points) did not change. *: statistically significant; NS: no statistical significance.