Heparin Induced Extracorporeal LDL Precipitation (H.E.L.P.) in Treatment of Tinnitus: A Randomised, Multicentre Trial

Abstract

Abstract:Background: At the beginning, cochlear tinnitus seems to arise from a dysfunction of cochlear outer hair cells. Similar to other inner ear disorders a disturbance of cochlear microcirculation is one of the most frequently discussed reasons. Animal studies and clinical evidence show a negative effect of high cholesterol and fibrinogen on hearing function. Acutely lowering serum LDL and fibrinogen by means of LDL and fibrinogen apheresis increases cochlear blood flow and has been proven to be effective in treatment of idiopathic sudden sensorineural hearing loss. Therefore we aimed to determine whether acute reduction of plasma fibrinogen and serum LDL is effective for treatment of subacute tinnitus. Methods:Between January, 2004 and December, 2006 we included patients of 18 through 80 years of age suffering from subacute cochlear tinnitus between 3 to 12 months on one or both ears and having serum LDL-cholesterol between 130 and 190 mg/dl. Tinnitus was evaluated using a standardised questionnaire designed by Goebel and Hiller. Patients meeting inclusion criteria were provided with the HMG-CoA reductase inhibitor simvastatin 40 mg once daily for 3 months. This procedure was done due to ethical reasons to reduce cholesterol and LDL non invasively in a first step. After 3 months tinnitus was re-evaluated and patients were excluded from the study if severity fell by more than 20 on the tinnitus score. 27 included participants were randomly assigned in a one to one ratio either to triple fibrinogen/LDL apheresis or triple sham therapy. Differences between tinnitus score on the day of randomisation and after 12 weeks were used as main outcome measure. Development of tinnitus score after every treatment, differences in loudness and frequency of tinnitus (masking and matching) after every treatment and after 12 weeks and the development of hearing thresholds after 12 weeks were used as secondary outcome measures.Findings: Main outcome measure tinnitus score 12 weeks after first therapy showed no significant differences between the groups. Though, there was a strong tendency towards an relieve of tinnitus in the apheresis group (p = 0.069 for the difference of the baseline value and the 12 weeks value between apheresis vs sham-therapy). Neither pure tone thresholds after 12 weeks, nor tinnitus masking and matching after every therapy and after 12 weeks showed significant differences between the groups.Conclusions: In our study, all patients suffered from subacute tinnitus and tinnitus score was stable or slightly worse in the placebo group over time. The improvement of tinnitus score in the apheresis group -although not statistically significant -is therefore a remarkable observation. For a more conclusive evaluation of this observation further studies with a larger number of patients should be conducted.