Softening the sound of the Big Easy is difficult. Even when no saints are marching in from a football victory and the streets aren't rocking with Mardi Gras, New Orleans is home to all that jazz. The city council, which has been trying for the past few years to pass a new noise ordinance, has so far met with loud and brassy opposition.
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So you might think that, a few blocks from the business district over at Xavier University, Joe Melcher, PhD, a highly regarded audiologist, would welcome an experimental pill aimed at hearing preservation, a tablet that helps protect against inner-ear damage. But Dr. Melcher, a professor of speech pathology and audiology, isn't so sure. After all, he doesn't even recommend antioxidant supplements, which largely make up one of the compounds being studied. “My knowledge of that chemical area is very limited,” he explained. “Until further studies have been done and approved by the FDA, I am hesitant.”
Dr. Melcher isn't alone. Despite a fairly extensive track record on animals, the approach has failed to ignite the same kind of anticipation among audiology professionals that it seems to have aroused in consumer publications. (HealthDay News, Feb 19, 2009; see FastLinks.)
“I would be interested in looking at the studies, and doing my own analysis” before taking any antioxidant supplement, said Ellen Mathis, a volunteer for the California Hearing Loss Association and a former systems analyst. She lost much of her hearing as a result of genetic inheritance, but she doesn't want to lose any more due to age-related decline. So what would it take for her to initiate such an oral regimen? Good evidence, she said. And there seems good reason for reluctance on the part of people like her and Dr. Melcher.
The audiology profession has long debated how best to deliver these possible ear-protective antioxidants — food is suggested as the most effective route to the human system. (Audiology Today, July/August 2011; see FastLinks.) But some audiologists adopted a new method — seemingly a more patient-friendly one — only to learn the former way was as good or better. They replaced oral steroids with injected ones, a change made at least in part to spare some the side effects of ingested steroids. But a side-by-side comparison showed these two delivery techniques to be comparable, and the oral one is a fraction of the cost of injection. (NIH News, May 24, 2011; see FastLinks.)
Ototoxicity is increasing, partly due to treatment with certain medications, some of which are used to treat infection, others for cancer therapy. This adverse effect can have severe consequences, particularly in individuals with prior hearing loss. To catch and counter the process early, a team of researchers from the Portland VA Medical Center and the Oregon Health & Science University in Portland, OR, have developed an ototoxicity-monitoring program designed to detect the first signs of damage. (Semin Hear 2011;32:248.)
Other reasons for hearing losses don't seem subject to such vigilance. Estimates vary on how much deterioration is occurring among earbud-wearing youth, but national data now show that one in every six U.S. adolescents has high-frequency hearing loss. (See FastLinks.)
In recently published studies on chinchillas, auditory changes from high-decibel exposure were linked to immunohistological changes, which were largely reversed with antioxidant treatment. (Int J Otolaryngol 2011; Article ID 612690; see FastLinks.)
It is only one of many studies over the past several years to show that certain therapeutic agents seem able to combat acute acoustic trauma at the cellular level by scavenging the injurious free radicals created in the event. (Semin Hear 2011;32:201.) One of those rescue agents, N-acetylcysteine (NAC) is used as a substrate for glutathione synthesis, and inhibits stress-induced cell death and curbs the inflammatory response due to injury, said Richard Kopke, MD, an otolaryngologist, who has been working on NAC in his research. He noted that so far one human study on Taiwan factory workers showed protection against noise-induced loss, as demonstrated by temporary threshold shift, by using NAC in conjunction with a nitrone compound. (Hear Res 2010;269[1-2]:42.)
“But we don't know what one [of these] is going to be the most effective one because, for the most part, there are only animal studies published so far,” said Dr. Kopke, the chief executive officer of the Hough Ear Institute in Oklahoma City.
Because there are no published data from human trials on a large scale, “there are no guarantees” which oral therapeutic agent will be most successful in mitigating noise-induced hearing loss, agreed Kathleen Campbell, PhD, a professor of otolaryngology at Southern Illinois University School of Medicine in Springfield and Carbondale.
Dr. Campbell has been investigating otoprotective oral agents, too, and she considers D-methionine promising. “In every animal study, as well as in small human studies, it has been shown protective” against hearing loss, she said.
Just beginning are two different studies that will test oral agents as a defense against hearing loss from acute noise. In one, a traditional pharmaceutical will be used; in the other, it's an antioxidant formulation, according to lead researcher Colleen Le Prell, PhD, an associate professor in the department of speech, language, and hearing sciences at the University of Florida in Gainesville. “Some sounds seem just too loud for hearing protection,” Dr. Le Prell explained, adding that even the most successful sound-buffering ear technology doesn't prevent certain wave transmissions from penetrating temporal bone. It makes sense that a pill would allow fast protection post-exposure.
“What everyone is waiting for is human data,” she said. The antioxidant compound, ACEMg, which is to be used in the trial and for which she is co-inventor, contains beta carotene, vitamin C, magnesium, and vitamin E, among other ingredients. The precise process involved in hearing preservation by this approach is not yet fully understood, but magnesium is known to preserve blood flow, and these vitamins act to scavenge free radicals directly.
The pharmaceutical and ACEMg have shown evidence of conferring protection against hearing loss in studies with animal subjects. Now Dr. Le Prell and fellow researchers will soon conduct the first U.S. double-blind, placebo-controlled trials to determine whether they are preventive against temporary hearing loss. In the studies, earphones will be used to transmit loud music to student volunteers, causing temporary hearing changes that are quickly and completely reversible.
A pretest assessment will occur during the enrollment period of each study, which will be used to determine hearing capacity. The first tests will follow the informed-consent process. Once that has been provided by enrollees, a second test will be given to establish individual baselines. After a four-hour interval of music, testing will be done at 15-minute intervals, and recovery will be tracked for three hours, the following day, and one week later to ensure complete recovery to individual subject baselines.
It is well known that there is substantial individual variability in vulnerability to noise-induced hearing loss, and even in this relatively homogeneous college student population, there have been individual differences in vulnerability, with some subjects showing no temporary changes in hearing function, she noted.
Previous studies in Sweden on military personnel — an investigation on which Dr. Le Prell served as the lead author — didn't demonstrate a measurable protective effect with ingested capsules similar to the kind Dr. Le Prell and her colleagues are now testing because the noise insult did not induce any reliable hearing loss against which protection could be measured. Among a subset in this group — those found to be most vulnerable to the noise of guns being fired — the strategy did appear protective against hearing loss on the day of shooting practice.
All three investigators — Drs. Le Prell, Campbell, and Kopke — have patents on the compounds they are testing, and the institutions they worked for at the time are legal holders as well. In fact, Dr. Kopke said he doesn't expect to get much financial remuneration, but he is bothered by the lack of progress just the same. After all, human trials are only now commencing. Although the one he undertook involving members of the armed services was conducted years ago, the publication of it has been delayed. “I wish the whole thing were faster,” he said.
After the studies are completed, there is a long wait for U.S. Food and Drug Administration approval, and even then, cautionary habits may prevail for a while. Suppose a simple vitamin is found to be protective against hearing loss, even restorative? “I can make patients aware of the studies that have been done, and if they want to try it themselves, OK,” Dr. Melcher said.
• Read the HealthDay News article on a pill for preventing hearing loss at http://bit.ly/PreventPill.)
• The Audiology Today article on ear-protective food is available at http://bit.ly/EarProtective.)
• Read the NIH News article about replacing oral steroids with injected ones at http://1.usa.gov/w4YzOI.)
• National data show that one in every six U.S. adolescents has high-frequency hearing loss: http://bit.ly/HearingLossEarbuds.
• A study using chinchillas found auditory changes from high-decibel exposure were largely reversed with antioxidants: http://bit.ly/xx69AV.
• Click and Connect! Access the links in The Hearing Journal by reading this issue on thehearingjournal.com.
• Comments about this article? Write to HJ at HJ@wolterskluwer.com.
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