Sudden Sensorineural Hearing Loss

The annual incidence of sudden sensorineural hearing loss (SSNHL) is 5 to 20 per 100 000 persons. The pathophysiology of SSNHL and acute vestibulo-cochlear syndromes (VCS) is unknown in more than 70% of cases. Hypothesis : an inner ear microvascular disease represents the key element in the pathogenesis of SSNHL and acute VCS. Plasma serotonin has among other tissular effect a vasospastic on microcirculation such as the inner ear microvascularisation. Increased plasma homocysteine has a deleterious effect on vascular endothelium. Inner ear microvascularisation sensitized by an increased homocysteine level and the vascular wall would vasoconstrict under serotonin stimulation inducing ischemia of the vestibular and/or cochlear organs.

The goal of this 2 step-up, exploratory study is to test safey, tolerability and PK/PD profiles in healthy volunteers and safety, tolerability and efficacy in sudden sensorineural hearing loss patients as an early salvage therapy. The main questions it aims to answer are: 1. whether is it safe and tolerable when healthy volunteers and sudden sensorineural hearing loss patients take multiple doses of NS101 against FAM19A5 2. whether is it effective in reversing hearing capability in sudden sensorineural hearing loss patients who fails to show sufficient recovery despite of oral standard steroid therapy. Patients and heathly volunteers will be given NS101 15mg/kg or 30mg/kg systemically less than 3 months per protocol. This is placebo controlled, double blinded study, which means there will be a group who receives placebo (i.e. fake drug) for study purpose.

Context: Idiopathic Sudden Sensorineural Hearing Loss (ISSHL) is a rapid-onset, sensorineural hearing loss of unknown etiology. It is one of the most common ENT emergencies, with spontaneous recovery occurring in 32% to 65% of cases. Treatment remains controversial, and the need for treatment itself is debated. Oral corticosteroids (OCS) are commonly used as first-line therapy, although they may have short-term side effects. Intratympanic corticosteroid injections (ITCIs) are an option for patients with contraindications to OCS or as a salvage treatment. The most recent Cochrane review includes three placebo-controlled studies on OCS efficacy (totaling 267 patients): two found no superiority of OCS, while one showed improvement in hearing. These studies are inconsistent and present methodological biases. Therefore, a sufficiently powered study is needed to assess OCS efficacy and establish clear treatment recommendations for ISSHL. Objectives: Primary Objective: To demonstrate the equivalence of OCS as first-line treatment for ISSHL compared to no treatment, in terms of hearing recovery between days 7 and 10. Secondary Objectives: To assess the effect of OCS versus no treatment on tinnitus, and hearing recovery based on initial severity of ISSHL. To evaluate hearing recovery in patients treated with rescue ITCIs. In the absence of equivalence, to investigate the superiority of OCS over no treatment. Methods: This multicenter, randomized, controlled equivalence trial will include two arms, each with 215 patients: one receiving OCS and the other a no-treatment control. In the absence of early hearing improvement, ITCIs will be administered regardless of study arm. Perspective: The goal is to clarify the role of OCS in treating ISSHL and guide the development of updated treatment recommendations.

The goal of this clinical trial is to learn which one works to treat better in patients with sudden sensorineural hearing loss, oral or intratympanic corticosteroid treatment. The main question it aims to answer is: Which corticosteroid treatment is more effective in patients with sudden sensorineural hearing loss, oral or intratympanic? * In our study, it was planned to divide the treatment schemes compared into two groups. Group 1 included patients who received oral methylprednisolone treatment daily for 2 weeks (48 mg for the first 7 days, 32 mg for the following 2 days, 16 mg for the 2 days, and 8 mg for the last 3 days). Group 2 included patients who received intratympanic 8 mg/2 ml dexamethasone every other day, totally 4 doses. * Visit the clinic after diagnose in first week, second week, first month and second month for checkups and tests ( temporal MR, odimetric results)

A small clinical trial for idiopathic sudden sensorineural hearing loss (ISSNHL). Will the addition of an oral statin to the standard treatment (oral methylprednesolone and the salvage therapy of intratympanic dexamethasone) improve the treatment outcome for patients with ISSNHL? This study will compare the two treatments and quantitatively evaluate hearing and speech discrimination and have the patients subjectively evaluate tinnitus.

The goal of this observational study is to describe the multi-omics characteristics and to learn about the prognostic factors in patients with idiopathic sudden sensorineural hearing loss (SSNHL). The main problems it aims to deal with are: * if there is a difference in data of exome and targeted sequencing among patients with SSNHL affecting bilateral and unilateral sides, and healthy controls * if there is a difference in the parameter of MRI among patients with SSNHL affecting bilateral and unilateral sides, and healthy controls * to find out which factor from multi-omics data relates to outcomes of SSNHL * to develop the best prognostics model based on the multi-omics data. Participants will be received audiological tests, blood specimen collection and radiological examination. Researchers will explore the relationship between the multi-omics data and the prognosis and develop the predictive model.