Clinical Trial of Etanercept (TNF-Alpha Blocker) for Treatment of Blast-Induced Tinnitus
Abstract
Tinnitus, often referred to as “ringing in the ears or head,” is scientifically defined as sound perception that occurs without an external acoustic event. When blast-related high-pressure shock waves are produced, or improvised explosive devices are detonated, the resulting sound levels can exceed 140 dB SPL. The intense noise exposures from military equipment operations, combined with the large overpressure created by detonation, inflicts injuries both to the ears and the brain. In the ears, blasts can perforate the tympanic membrane and damage hair cells, causing hearing loss. In the brain, blast shockwaves damage the nerve cells, causing traumatic brain injury (TBI). These problems often cause tinnitus, which is frequently accompanied by a variety of psychological disorders, including depression and anxiety. Clinical studies have demonstrated that blast injuries account for over 80% of combat-related injuries. Blast-induced neurotrauma and post-traumatic stress disorder (PTSD) are referred to as “signature injuries” of the Global War on Terrorism, with prevalence as high as 16% and 14%, respectively. As a result, the socioeconomic impacts of blast injuries have risen in public awareness. Tinnitus commonly occurs after blast injuries and is the number one diagnosis for Service-related disability claims. Among military personnel who have sustained blast injuries, 70% reported tinnitus symptoms within 72 hours of the exposure, while 43% reported that they suffered from persistent tinnitus 1 month afterwards. The annual cost to compensate Veterans for tinnitus in the U.S. is nearly $2 billion and rising. Tinnitus is often intensified by sounds that trigger “flash-backs,” and Service members who have both tinnitus and PTSD experience post-traumatic stress symptoms more frequently and with greater intensity than those with PTSD alone. Despite the great need, there is a lack of effective therapy for those who suffer from tinnitus, especially on a pharmacological level. To develop an effective treatment for tinnitus, this Phase II clinical trial will examine the therapeutic effects of Etanercept (Enbrel®), a tumor necrosis factor alpha (TNF-a) blocker, on blast- or noise-induced tinnitus. It is a Food and Drug Administration-approved and clinically proven safe medication. We hypothesize that Etanercept yields a therapeutic effect on tinnitus via acting on the immune system and mediating neural plasticity. TNF-a is known to play a critical role in many inflammatory conditions. In humans, it contributes to autoimmune cochleovestibular disorders, including hearing loss and tinnitus. Recently, Etanercept was used to treat microcirculation-related hearing loss after noise trauma. Taken together, these lines of evidence encourage us to conduct this clinical trial and test the central hypothesis that blocking TNF-a can reduce the severity of tinnitus for prolonged periods of time. Our hypothesis is based on supportive studies that blocking TNF-a not only reduces excessive inflammatory responses but also resets maladaptive neural plasticity that manifests in response to chronic stress from blast- or noise-induced tinnitus. We will test our central hypothesis by pursuing three specific aims: (1) Test for the therapeutic effect of Etanercept on blast-induced tinnitus in a double-blinded, randomized, placebo-controlled clinical trial. (2) Investigate the time course of the therapeutic effect of Etanercept on blast-induced tinnitus. (3) Identify contributing factors that influence the therapeutic effects of Etanercept on blast-induced tinnitus. To accomplish these aims, we will recruit military personnel, Veterans, or civilians with blast- or noise-induced tinnitus. Participating subjects will be given 12 weeks of Etanercept treatment. Audiological tests for hearing, tinnitus questionnaires, and visual numerical scale ratings will be used to examine the therapeutic effects of Etanercept on tinnitus at 1, 4, 8,
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810791
Entities
People
- Jinsheng Zhang
Organizations
- United States Army
- Wayne State University