Effectiveness and Safety of an Endothelial Protector Drug, Aminapthone, In Patients with Idiopathic Tinnitus

Subjective Idiopathic Tinnitus is a common and disturbing
condition characterized by an auditory perception of sound...


Introduction
Subjective Idiopathic Tinnitus is a common and disturbing condition characterized by an auditory perception of sound or noise that has no external source [1,2]. Almost 5% to 10% of people suffer from such condition (3-5 di 1) and this rate could increase up to 30% among the elderly [3]. Tinnitus very often becomes a "chronic condition" and may result in depression, anxiety, insomnia and, especially, "poor Quality of Life (QoL) in patients with such symptom. Currently no highly effective management therapy was recommended for Tinnitus despite a lot of treatments have been tried to control this condition. Microcirculatory disorders of the inner ear with a hemodynamic and metabolic imbalance of the endothelial leading to a damage of the cochlear cells, are often bring into play in the classical cochleovestibular symptoms such as tinnitus [4]. From the literatures seems to be clear the relationship between inner ear microcirculation dearrangements and Tinnitus: this is the reason why we try to use "an endothelial protector drug" such as AMINAPTHONE™, that has recently demonstrated to be effective in down-regulates molecules with key vasoactive roles such as E-Selectine and Endothelin 1 (ET-1) expression in vitro and in vivo [5][6][7] and to modulate the expression of endothelial inflammatory molecules that contribute to pathogenesis of several conditions where the endothelial dysfunction may play the main role, in particular in early events [8,9].

Materials and Methods
We have retrospectively analyzed data of sixteen patients (medium age 61.87 +/-13.68 years, 9 women and 7 men), affected by idiopathic chronic tinnitus afferent to ENT Unit of Ramazzini  [10][11][12] at baseline (T0) after 3 months (T1) and after 6 months (T2) of treatment (Table 2). We exclude from the analysis patients with inflammatory ear pathology or retrocochlear neurologic or neurosurgery pathologies; all patients had already tried other therapy without significant benefits. We exclude also patients taking steroid-drugs or NSAIDs (nonsteroidal antiinflammatory drugs). Characteristic of tinnitus: we indicated characterizes of tinnitus in frequency (Hz) and intensity (dB).

Results
All the 16 patients enrolled in this observational retrospective study complete the 6-month study period. No one patients presented adverse effects related to the study drug during the same time. Table 3     Referring to the secondary end-points (drop-out of the patients from the study during the sixth months of treatment and patient's compliance to treatment) all patients follow the six months courses of the Aminapthone treatment without adverse effects and with a good compliance to treatment: considering the kind of patients who always research a resolutive and immediately tinnitus treatment after have tried many other pharmaceutical an non treatment and the "usually loosing patients during a long-time treatment" we can conclude that Aminapthone treatment was "well-tolerated" (or well-accepted) from patients with a "good personal satisfactory index" for Aminapthone treatment and that, consequently, we have reach the secondary end-point of the study [13].

Discussion
Tinnitus is one of the most common hearing disorders; many risk factors has been individualized for this "stressing condition" such as age, hearing loss, inflammatory diseases or tumors of the ear, head or vertebral cervical trauma, ototoxic drugs, noise exposure and psychological disorders. Tinnitus could be a life-long disorder bringing to anxiety, depression, insomnia, hyperacusis, concentration difficulties and, sometimes, to suicide. QoL of people affecting by Tinnitus is often worsened leading to transform this hearing disorder in a "very serious disorder" involving "all the personal activity's area" of the patient. The inner ear diseases are often caused by microcirculatory disorders [14].

Figuerado and Coll, reviewing the association between arterial
hypertension and Tinnitus conclude that "there is evidence of an association between Tinnitus and Hypertension "and that "changes in the cochlear microcirculation, resulting in hearing loss, may be an adjuvant factor in Tinnitus pathophysiology" [15]. Interestingly, in the only 6 patients in which there were a deterioration of the THI at 6 months, we have observed a worsened in the audiometric performance: probably "the worsening of idiopathic chronic hearing loss pathology" was too strong to allow to endothelial protection to control Tinnitus. Nevertheless, the primary end-point of this observational study (THI improvement) has been significantly achieved after 3 months of treatment with AMINAPTHONE; probably an "plateau-effect" do not permit to obtain a statistically significative improvement after 6 months of treatment, but in all cases, there were no regression-effect. In conclusion, there is an association between TINNITUS and microcirculatory disorders. This association cannot be dissociated from the hearing loss, which was also more prevalent among Tinnitus patients. The use of drugs able to protect the endothelium damages has not been very well tested. Aminapthone is the first drug of a new drug's category: "the endothelial-protector drugs".
The preliminary and pilot results of this observational study seem to encourage the use of this new pharmacological treatment in terms of Qol improvement of patients and of patients' compliance to treatment. In future a prospective, controlled, randomized, double blind clinic study may confirm these preliminary but interesting results.