Evaluation of vardenafil for the treatment of subjective tinnitus: a controlled pilot study

Birgit Mazurek, Heidemarie Haupt, Agnieszka J Szczepek, Jörg Sandmann, Johann Gross, Burghard F Klapp, Holger Kiesewetter, Ulrich Kalus, Timo Stöver, Philipp P Caffier, Birgit Mazurek, Heidemarie Haupt, Agnieszka J Szczepek, Jörg Sandmann, Johann Gross, Burghard F Klapp, Holger Kiesewetter, Ulrich Kalus, Timo Stöver, Philipp P Caffier

Abstract

Background: Vardenafil (Levitra(R)) represents a potent and highly selective phosphodiesterase type 5 (PDE5) inhibitor, which is established for treatment of various diseases. There are several unpublished reports from patients stating that vardenafil has a considerable therapeutic effect on their concomitant tinnitus. This pilot study was conducted to specifically assess the effect of vardenafil in patients with chronic tinnitus.

Methods: This trial was based on a prospective, randomized, double-blind, placebo-controlled, parallel group design. Fourty-two consecutive subjects with mon- or binaural chronic tinnitus received 10 mg vardenafil (N = 21) or matching placebo tablets (N = 21) administered orally twice a day over a period of 12 weeks. Clinical examination and data acquisition took place at each visit: at baseline, after 4 weeks, after 12 weeks (end of treatment with study medication), and at non-medicated follow-up after 16 weeks. Assessment of clinical effectiveness was based on a standardized tinnitus questionnaire (TQ), the Short Form 36 health survey (SF-36), audiometric measurements (mode, pitch and loudness of tinnitus; auditory thresholds) and biomarkers of oxidative stress in patients' blood (malondialdehyde, protein carbonyl, homocysteine and total antioxidative status). Therapeutic efficacy was evaluated by comparison of subjective and objective parameters with baseline data between both treatment groups (ANCOVA).

Results: Vardenafil had no superior efficacy over placebo in the treatment of chronic tinnitus during this study. The primary efficacy criterion 'TQ total score' failed to demonstrate significant improvement compared to placebo. Subjective reports of TQ subscales and general quality of life areas (SF-36), objective audiometric examinations as well as investigated biomarkers for oxidative stress did not reveal any significant treatment effects. The safety profile was favorable and consistent with that in other vardenafil studies.

Conclusion: Although hypoxia and ischemia play a special role in the pathogenesis of tinnitus, the PDE5-inhibitor-induced increase of nitric oxide-mediated vasodilatation exerted no specific influence on tinnitus symptomatology. Considering the unclear risk of rarely associated hearing impairment, systemic application of vardenafil or other PDE5 inhibitors prove to be not appropriate for therapy of chronic tinnitus.

Figures

Figure 1
Figure 1
Flow chart of study population.
Figure 2
Figure 2
Time course of total TQ scores from baseline to week 16 with LOCF evaluated in vardenafil and placebo groups. Given are the LS-means and 95% confidence intervals of the ITT population.
Figure 3
Figure 3
Audiometric hearing thresholds from baseline to week 16 evaluated in left and right ears of vardenafil and placebo groups (ITT). For the sake of clarity, week 4 and LOCF data as well as whiskers are not shown.

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