title: Evaluation of vardenafil for the treatment of subjective tinnitus: a controlled pilot study.
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 There are several unpublished reports from patients stating that vardenafil has a considerable therapeutic effect on their concomitant tinnitus.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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otorhinolaryngology, Tinnitus Centre and Molecular Biology Research Laboratory, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. birgit.mazurek@charite.de
authors.forename: Birgit
authors.initials: B
authors.lastname: Mazurek
authors.forename: Heidemarie
authors.initials: H
authors.lastname: Haupt
authors.forename: Agnieszka J
authors.initials: AJ
authors.lastname: Szczepek
authors.forename: Jörg
authors.initials: J
authors.lastname: Sandmann
authors.forename: Johann
authors.initials: J
authors.lastname: Gross
authors.forename: Burghard F
authors.initials: BF
authors.lastname: Klapp
authors.forename: Holger
authors.initials: H
authors.lastname: Kiesewetter
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kalus
authors.forename: Timo
authors.initials: T
authors.lastname: Stöver
authors.forename: Philipp P
authors.initials: PP
authors.lastname: Caffier
mesh_terms: D001299:Audiometry; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D010879:Piperazines / Q000008:administration & dosage* / Q000627:therapeutic use; D011446:Prospective Studies; D013450:Sulfones / Q000008:administration & dosage / Q000627:therapeutic use; D014012:Tinnitus / Q000188:drug therapy* / Q000378:metabolism; D014227:Triazines / Q000008:administration & dosage / Q000627:therapeutic use; D000069058:Vardenafil Dihydrochloride
chemical_list: D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride