This new year is ringing in some exciting potential advancements in the field of audiology. From reducing the severity of noise-induced hearing loss to restoring hearing via regrowth of stereocilia, hearing professionals have reasons to be hopeful in 2017 and beyond.
“I have high hopes for clinical development and testing,” said Colleen G. Le Prell, PhD, audiology program head at the University of Texas at Dallas, where she is the Emilie and Phil Schepps Professor in Hearing Science. Le Prell is also the president-elect of the National Hearing Conservation Association. “In the last two years, we have seen larger pharmaceutical industry investment in the development and assessment of drugs for auditory indications. We have seen more attention than ever … I really believe that over the next five to 10 years we're going to see the first agents successfully emerge from the testing and approval process.”
NOISE-INDUCED HEARING LOSS
The American Hearing Research Foundation states that excessive noise exposure is the most common cause of hearing loss, and the National Institutes of Health (NIH) estimates that 15 percent of Americans aged 20 to 69 have high-frequency hearing loss as a result of occupational or leisure activities. Many baby boomers were exposed to high levels of noise before noise standards were in place, and thousands of U.S. soldiers involved in conflicts over the past two decades have been exposed to excessive noise as well. Among younger generations, noise-induced hearing loss is a significant risk due to the prevalence of portable music players and potentially risky listening habits http://bit.ly/2gKSLIX.
Le Prell has led or been involved in several studies assessing potential prevention of noise-induced hearing loss. One of the more recent clinical studies examined the potential efficacy of SPI-1005, a proprietary formulation of ebselen developed by Sound Pharmaceuticals, Inc. Ebselen is a synthetic organoselenium drug molecule that produces anti-inflammatory antioxidants and cytoprotective activity. SPI-1005 is administered orally to patients in pill form.
The study of 83 patients exposed to placebo or doses of 200, 400, or 600 mg of SPI-1005 resulted in “very good” protection against music-induced temporary threshold shifts. “We saw dose-dependent protection, with the most effective dose almost completely preventing temporary music-induced changes in threshold sensitivity,” Le Prell said. Subjects received a placebo or the drug prior to a single iPod sound exposure for four hours.
In an oral presentation of the findings in 2016, Le Prell and co-investigators stated that SPI-1005 treatment “demonstrated clinically relevant reductions in temporary threshold shift by loud sound exposure” and that multi-day doses were well-tolerated. “These data support the continued development of SPI-1005 in noise-exposed populations and the oral glutathione peroxidase mechanism of action in preventing and treating noise-induced hearing loss.”
Commenting on the music player model used in this and other studies, Le Prell said the music listening protocol results in a small but reliable temporary change in hearing across subjects. “I have frequently referred to this as a proof-of-concept model,” she said. “The changes induced with the music player don't reach a clinically relevant loss of hearing. But demonstrating a reduction in or prevention of this small change in hearing provides evidence that the agent of interest can access the inner ear and act on the mechanism that causes hearing loss.
“If you think about occupational noise injury, noise-induced hearing loss affects a large number of people but progresses slowly,” she continued. “The slow timescale for progression makes clinical trials more time-consuming and more costly. Having evidence from this kind of lab-based study—data showing that a drug potentially has benefit—could encourage more research in clinical populations. I see the utility of this model being the laying of groundwork for more investment and research.”
At least one more company is researching a potential treatment for noise-induced hearing loss. The NIH clinical trials reporting site, ClinicalTrials.gov, shows that MetArmor is studying the potential application of D-methionine (D-met) to reduce noise-induced hearing loss and tinnitus. A Phase 3 trial of an oral liquid suspension formulation of D-met is under way as of fall 2016 and is scheduled for completion in December 2017. This prospective study is a randomized, double-blind, placebo-controlled clinical trial. The study population is a cohort of drill sergeant instructor trainees during and 22 days after their 11-day weapons training. The primary objective is to determine the efficacy of D-met in preventing noise-induced hearing loss or reducing tinnitus secondary to a minimum of 500 rounds of M-16 weapons training.
In the area of profound hearing loss, aggressive research is targeting a potential gene therapy. GenVec, Inc., and Novartis AG have partnered to study the use of an atonal gene (Atoh1) to treat this condition.
During embryonic development, Atoh1 induces the differentiation of sensory cells in the inner ear. In multiple animal models, GenVec has demonstrated the formation of new inner ear sensory hair cells and the restoration of hearing and balance functions using its gene delivery technology to deliver Atoh1 to the inner ear. GenVec partnered with Novartis to bring this potential therapy into human testing and development. The compound in clinical trials is known as CGF166.
Columbia University in New York City and the University of Kansas Hospital in Kansas City are two facilities involved in a multicenter, open-label, single-dose study of CGF166 in patients with severe to profound hearing loss. The study seeks to evaluate the safety, tolerability, and potential ability of CGF166 to improve hearing and vestibular functions. The therapy is delivered via intra-labyrinthine infusion.
A BOOTS-ON-THE-GROUND PERSPECTIVE
Audiologists who work in typical patient care settings may not be involved in clinical research directly, but they are attentive to it and have distinct opinions about where it should be headed. Alicia D.D. Spoor, AuD, president of Designer Audiology in Highland, MD, told The Hearing Journal that she believes research should be expanded in size and scope.
“I think the profession of audiology needs larger studies,” she said. “Many studies have great outcomes, but the number of participants is extremely limited, as few as six or 25 subjects.”
She added: “I also think the areas being studied need to be expanded to include the full scope of audiology: diagnostics and treatment of hearing, tinnitus, cochlear implants, amplification, balance, and more.”
Spoor pointed out that much hearing research is conducted in university or government (e.g., NIH and Veterans Health Administration) settings rather than in clinical settings. “This may skew some results,” she said. “…I would like to be able to complete some clinical research, collaborating with researchers who are interested in doing the background work, such as literature searches and statistics, and then working together to write the study.”
For D'Anne Rudden, AuD, of Longmont Hearing and Tinnitus Center in Colorado, these exciting new avenues are vital in delivering better hearing care to the end user. “To stay ahead of the curve, I must know what potential innovations are coming down the road,” she explained. “The clinics of tomorrow embrace evidence-based practices into their daily routines, maximizing efficiencies and delivering cost-effective care. This is how we continue to stay relevant in our ever-changing arena.”
In many ways, clinical research is part of patient education. “Knowing about the latest advancements in hearing research gives us greater opportunities to educate patients, their family members, and our communities that audiology is a patient-focused health care profession—from research inception to practical application,” said Rudden.
Like Spoor, Rudden expressed the importance of more collaboration between researchers and independent practices. “As the profession's entrepreneurs, private practitioners are often the first to look outside the box’ and find creative ways to maximize patient care AND cost-effectiveness.” Citing some examples, “Practicing audiologists could participate even more directly with researchers to design clinical protocols and practical documentation methods, provide beta-testing feedback as well as acting as community liaisons for patient/family outreach to assure best measurable outcomes.”
Heading into 2017, the outlook for advancements in audiology is strong, particularly where the treatment of hearing loss is concerned.
“I want to emphasize the sense of enthusiasm that myself and so many others have in terms of the bulk and variety of research moving forward,” Le Prell said. “I believe there is significant promise that one or more agents will ultimately emerge as successful for the prevention of, and perhaps even the treatment of, hearing loss.”
This article highlights just a few of the promising research trials and studies under way in the U.S. Status of others include:
- A potential treatment for sudden hearing loss is in development. Auris Medical AG has begun enrolling patients in a Phase 3 trial of single-dose intratympanic AM-111. This trial is a randomized, double-blind, placebo-controlled study that will evaluate the efficacy, safety, and tolerability of single-dose AM-111 administered within 72 hours of the onset of hearing loss.
- The first potential treatment for tinnitus may have experienced a setback. Keyzilen (also developed by Auris Medical), which has completed Phase 3 trials, would be administered after traumatic cochlear injury or acute otitis media. In Phase 2 trials, the gel was well-tolerated and showed dose-dependent and persistent improvements in tinnitus loudness and other outcomes. After these findings were released, the Food & Drug Administration awarded Keyzilen fast-track status due to the pressing need for tinnitus treatment. However, the first Phase 3 findings did not meet the two co-primary efficiency endpoints of statistically significant changes in tinnitus loudness and tinnitus burden compared with placebo. Results of the second Phase 3 trial had not been released when this article went to press.