Tinnitus Treatment Tackles Underlying Mechanisms

Nancy A. Melville

January 15, 2018

An experimental intervention combining auditory and mild electrical pulse stimulation shows potential as a novel neurologic approach to tinnitus, an often debilitating condition that is difficult to treat.

"The neural desynchronization strategy presented here offers a new and accessible treatment possibility for tinnitus sufferers," said the authors, led by Susan Shore, PhD, from the University of Michigan's Kresge Hearing Research Institute in Ann Arbor.

The device, developed by the team at the University of Michigan, uses targeted bimodal auditory-somatosensory stimulation, in which sounds that are emitted into the ear through inserted earphones are alternated with precisely timed weak electrical pulses to the cheek or neck.

The approach is designed to "reset" the activity of fusiform cells, which, located in the dorsal cochlear nucleus region of the brainstem, normally help the brain tune out sensations related to the movement of the head and neck. As the researchers have previously reported, those cells are altered in tinnitus.

In the first study to evaluate the approach in humans, published January 3 in Science Translational Medicine, 20 patients with tinnitus were randomly assigned in a crossover design to receive either 4 weeks of daily 30-minute sessions using the take-home device, which was calibrated to the loudness and pitch of the phantom sounds in the patients' unique tinnitus symptoms, or a sham treatment involving only sounds and no stimulation.

After the 4 weeks and a 4-week washout break, each group was switched to the alternative treatment regimen.

Overall, the active treatment was associated with significant decreases in the loudness of phantom sounds (P < .05), assessed according to cumulative measures on TinnTester software of how loud patients' tinnitus sounds were, whereas no improvements were associated with the sham treatment.

The loudness reduction reached an average of 12.2 decibels in the fourth week of treatment in the active treatment group, with patients reporting that their tinnitus was less "harsh" or "piercing" and more "mellow," and two patients reported complete elimination of their tinnitus by the end of the period.

The intrusiveness of tinnitus and quality of life also improved with the active treatment, with mean overall scores on the Tinnitus Functional Index (TFI) decreasing from baseline of 29.2 units to 22.9, with a lower score representing less impact from tinnitus.

Ten of the 20 participants had TFI reductions of at least 13 points during treatment, considered clinically meaningful.

The improvements in TFI unexpectedly remained unchanged into the 4-week washout period, which was not observed in with the loudness reduction, Dr Shore told Medscape Medical News.

"This was a surprise — we expected [TFI] to mimic the loudness decrements," Dr Shore said. 

"Since both the loudness decrements and the TFI scores decreased cumulatively over the 4 weeks of treatment and took a week to several weeks to return to baseline, we expect that longer duration treatments should lead to longer lasting effects."
 

Targeting Tinnitus Mechanisms

Importantly, the study criteria required that patients display a somatosensory component of their tinnitus symptoms, which is reported in about 60% to 80% of patients with tinnitus and is evident in the ability to temporarily alter symptoms with movements such as jaw clenching, sticking out their tongues, or turning or flexing their necks.

Such symptoms suggest the potential for an external somatosensory signal to alter the activity of fusiform cells, Dr Shore explained in a press statement.

"[When] fusiform cells become hyperactive and synchronize with one another, the phantom signal is transmitted into other centers where perception occurs," she said.

"If we can stop these signals, we can stop tinnitus," she said. "That is what our approach attempts to do, and we're encouraged by these initial parallel results in animals and humans."

The study in humans helped to validate extensive preclinical studies. All have consistently shown responses only with the two alternating stimuli and do not show improvements with exposure solely to the sound pulses.

The authors are moving ahead with a larger clinical trial with funding from the National Institutes of Health. The study will have a planned enrollment of 50 participants and will extend the treatment from 4 to 6 weeks, Dr Shore said.

Should the findings in humans be replicated, Dr Shore said, she envisions that the device could represent a convenient in-home tinnitus treatment.

"The devices are take-home, so it is possible that in the future when this becomes commercialized,  users could use them as needed once an initial treatment has shown efficacy."

The University of Michigan has a patent on the concept and is pursuing its potential commercialization.

Current Tinnitus Treatments Limited

The need for an effective treatment of tinnitus is pressing, with current treatments focusing largely on patients' psychological responses to their symptoms, explained Nancy Mueller, MD, an associate professor of neurology at the New York University Langone Medical Center.

"The study is significant as it addresses the treatment of the etiology of chronic tinnitus," Dr Mueller told Medscape Medical News.

"Most treatments that are used now are related to relieving the symptomatology of tinnitus, ie, anxiety, distress, et cetera."

"This approach is innovative and creative," she added. "It advances the idea of not only the plasticity of the fusiform, stellate and cartwheel cells, but also the different neurotransmitters and receptors at the cellular level."

Other neurologic approaches that have been evaluated for tinnitus treatment include the pairing of tones with vagus nerve stimulation, as described in a recent report in Nature.

But Dr Mueller noted that those interventions have important limitations.

"Both vagal nerve stimulation with or without the bimodal treatment and deep brain stimulation have been investigated, but due to the invasiveness, possible unwanted outcomes, maintenance and limitations of future use of magnetic resonance imaging, their use will be limited to a very small portion of the population of patients with chronic tinnitus," she said.

"This approach appears to have the possibility of being noninvasive, easily used, and available to many patients with chronic tinnitus."

Tinnitus affects 15% of the population in the United States and represents the most prevalent service-connected disability for military personnel, the authors explained.

About 10% of those with tinnitus report being bothered by the disorder, and as many as 2 million are severely debilitated.

The study received funding from National Institutes of Health grants and the Wallace H. Coulter Translational Research Partnership. Dr Shore is an inventor on the US patent for the concept. Dr Mueller has disclosed no relevant financial relationships.

Sci Transl Med. Published online January 3, 2018. Abstract

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