ObjectiveTo evaluate the efficacy and safety of intratympanic AM-101 in patients with persistent acute inner ear tinnitus after acute acoustic trauma, idiopathic sudden sensorineural hearing loss (ISSNHL), or acute otitis media.Study DesignProspective, double-blind, randomized, placebo-controlled study with follow-up visits on Days 7, 30, and 90.SettingTwenty-eight European sites (academic tertiary referral centers and private ENT practices).Patients248 patients aged 16 to 65 years.InterventionsThree intratympanic injections of AM-101 (0.27 or 0.81 mg/ml) or placebo over 3 consecutive days.Main Outcome MeasuresEfficacy was assessed by changes in minimum masking level (MML; primary end point), loudness match, tinnitus loudness, tinnitus annoyance, and sleep difficulties on a 0 to 100 numerical rating scale, THI-12 questionnaire, and patient global impression of change. Safety was evaluated using the frequency of clinically relevant hearing deterioration and adverse events.ResultsThe study overall failed to demonstrate a treatment benefit based on the change in MML. However, AM-101 0.81 mg/ml showed statistically significantly better improvement for tinnitus loudness, annoyance, sleep difficulties, and tinnitus impact in patients with tinnitus after noise trauma or otitis media. The subgroup of ISSNHL-related tinnitus patients did not show conclusive results. The study drug and I.T. injections were well tolerated.ConclusionThe study established proof of concept for AM-101 in the treatment of tinnitus arising from cochlear glutamate excitotoxicity. Patient-reported outcomes seem to be more relevant and reliable efficacy measures for assessing treatment-related changes in tinnitus than psychoacoustic tests.
Effective pharmacological treatments for tinnitus have proven elusive. Emerging evidence suggests that dysregulation of cochlear N-methyl-D-aspartate (NMDA) receptors may underlie aberrant excitation of the auditory nerve, which in turn is perceived as tinnitus. The blocking of these receptors thus represents a promising therapeutic approach. In a recent phase I/II clinical trial, the safety and local tolerance of intratympanic injections of the NMDA receptor antagonist AM-101 was evaluated for the first time in humans. The results from the double-blind, randomized, placebo-controlled study show that intratympanically injected AM-101 was well tolerated by study participants, and provided the first indications of therapeutic efficacy.
Allergen-specific immunotherapy for grass pollen allergy has been reported to be effective in up to 85% of patients. Sensitisation to profilin and calcium-binding protein (CBP) can possibly influence treatment results and may thus be a reason for treatment failures. During a study period of 3 years, the distribution patterns of antibodies to marker allergens were continuously investigated in all blood serum samples with a level of immunoglobulin E antibodies to timothy and birch pollen higher than 0.7 kUA/l (n = 556). Sensitisation to timothy grass pollen alone was found in 33% of the cases, to birch pollen alone in 19%, and to both in 48%. The group of polysensitised patients showed an inhomogenous distribution of antibodies to marker allergens. IgE against minor allergens was detected in 40%. Sensitisation to major allergens, especially to the major birch allergen, was not present in 13% of the polysensitised patients. Of the patients who were sensitised to minor allergens, 82% were sensitised to profilin, 11% to CBP, and 8% to both profilin and CBP. Profilin and CBP frequently cause polysensitisations to pollen. The data obtained justify the measurement of serum levels of antibodies to marker allergens in patients who are sensitised to more than one group of allergens.
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thresholds in 500 Hz, 2000Hz, and tritonal mean (P = 0.003, P = 0.03, and P = 0.02, respectively) Conclusions: The posterior mesotympanic cholesteatomas had greater air-bone gap thresholds in the speech frequencies when compared with posterior epitympanic cholesteatomas. However, the two growth patterns were very similar in the other audiometric parameters.Objectives: Glutamate excitotoxicity following cochlear trauma can trigger aberrant excitation of the auditory neurons, resulting in tinnitus. AM-101, a small molecule NMDA receptor antagonist, has shown evidence of preventing onset of tinnitus in animal models of cochlear trauma after intratympanic delivery. We present the results of the European and U.S. phase II clinical trials.Methods: Three hundred and twenty subjects with persistent tinnitus were enrolled in a double blind placebo controlled trial of AM-101. Efficacy endpoints included change in subjective tinnitus loudness, annoyance, sleep difficulties, the THI-12 questionnaire, and minimum masking level and loudness match. A patient global impression of change assessed the change in tinnitus severity over the study duration.Results: A dose dependent and statistically significant improvement of tinnitus loudness, annoyance, sleep difficulties, and the THI-12 over placebo could be demonstrated in subjects with tinnitus following acute noise trauma or otitis media. The improvement was most pronounced in the AM-101 810 µg/ mL treatment group and continued to increase to Day 90 of the study. In contrast, the subgroup of sudden hearing loss related tinnitus did not show an improvement in tinnitus. The study drug was well tolerated. Conclusions:The study established human proof of concept for application of AM-101 in the treatment of tinnitus arising from cochlear glutamate excitotoxicity. Local delivery of AM-101 in a defined patient population in the acute stage of injury allows for a substantial and persisting attenuation of tinnitus with minimal systemic exposure and side effects. Clinical Use of a Novel, single-Dose Treatment for Bacterial or Fungal Otitis ExternaMatthew P. Branch, MD (presenter); Vance J. OglesbeeObjectives: To assess the efficacy of a novel, single-dose, physician-administered viscous suspension for treatment of either acute bacterial otitis externa (ABOE) or fungal otitis externa (FOE).Methods: Eighty-nine consecutive patients seen by a single author in an outpatient, private practice clinic were diagnosed empirically with either ABOE (n = 52) or FOE (n = 37) based on patient symptoms, appearance of the external auditory canal, and presence or absence of fungal elements. All external auditory canals were debrided when necessary under microscopy, then filled with a viscous otic suspension containing clotrimazole 1%, ciprofloxacin 0.3%, and dexamethasone 0.1%. The canal was occluded with a cotton ball, and patients were followed up at various intervals.Results: Of the 52 ABOE patients, 48 experienced complete symptom resolution at 2.5 days on average and all patients had complete resolu...
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