Armed and Exposed Audiologist Kathleen C. M. Campbell is on the front lines of studying a drug that could protect soldiers from long-term hearing loss—and save the U.S. Armed Forces billions of dollars. Features
Features  |   January 2016
Armed and Exposed
Author Notes
  • Haley Blum is a writer/editor for The ASHA Leader.
    Haley Blum is a writer/editor for The ASHA Leader.×
  • © 2016 American Speech-Language-Hearing Association
Article Information
Hearing Disorders / Regulatory, Legislative & Advocacy / Features
Features   |   January 2016
Armed and Exposed
The ASHA Leader, January 2016, Vol. 21, 46-51. doi:10.1044/leader.FTR2.21012016.46
The ASHA Leader, January 2016, Vol. 21, 46-51. doi:10.1044/leader.FTR2.21012016.46
The jarring rat-tat-tat of gunfire. The piercing blast of an IED. The constant roar of convoy engines.
Soldiers are exposed to a barrage of potentially damaging noises, so it’s not surprising that hearing impairment, including tinnitus, is one of the most common injuries sustained by soldiers during their service, according to the Department of Defense’s (DoD) Hearing Center of Excellence. Earplugs and earmuffs are available, but they still don’t fully protect against some sounds.
The military has a hearing loss problem. And Kathleen C. M. Campbell is trying to solve it.
The Southern Illinois University School of Medicine professor and audiologist has spent 20 years developing a micronutrient called D-methionine (D-met). Now she’s in the midst of a Phase 3 clinical trial at Fort Jackson in South Carolina, looking to see if the liquid form of the drug can protect against noise-induced hearing loss in a population exposed to repeated rounds of noisy weapon fire—each shot reaching 155 decibels—during drill-sergeant training.
With $2.9 million from the DoD, and additional funding from NIH, Campbell is focused on the military. But if this type of preventive drug succeeds, the impact would extend far beyond the base.
You’re studying D-methionine in Fort Jackson as a drug that could possibly prevent noise-induced hearing loss. What is it?
D-met is an amino acid and a component of protein. In most proteins, the methionine content is L-methionine, but in fermented proteins it changes to the mirror-image molecule, D-methionine, which is even safer and has better protective properties. And it is a micronutrient, and it’s present in fermented proteins in foods like yogurt and cheese.
Your study is a Phase 3 trial. What has the development process of this drug been like? You’ve been working on it for quite a few years now.
Yes, I have. It’s been a long process—I’ve been working on developing the drug for two decades, and we have five U.S. patents issued. I’m the sole inventor, but my school, Southern Illinois University School of Medicine, owns the patents.
I started out testing D-met for cisplatin-induced [chemotherapy] ototoxicity and it works. We’ve done a Phase 2 clinical trial for that and it was successful—we got significant protection. And then we’ve also used it for radiation-induced oral mucositis, which is kind of a different topic. And we have good protection of aminoglycoside-induced [antibiotics] ototoxicity, but that’s preclinical work.
Why did you initially pursue this area of research?
I was a clinical audiologist for many years, and some of the patients that I had were dissatisfied with how much we could help them with noise-induced hearing loss and drug-induced hearing loss because they cannot be cured—it’s permanent. And they don’t always do well with hearing aids. I don’t want to denigrate hearing aids at all, because they help a lot of people a great deal, but they do not restore normal hearing, as anybody with hearing aids will tell you. So I just wanted some better solutions.
I was interested in noise-induced hearing loss because we see it every day in our audiology clinics and it’s the most common cause of hearing loss worldwide. And people with drug-induced hearing loss are also sometimes dealing with life-threatening illnesses. To lose your hearing and your ability to communicate easily over the telephone, at a time when you really need to connect with your family and friends—who are frequently scattered around the country, if not the world—is devastating.
Why is noise-induced hearing loss such an issue in the military?
It’s costing the DoD and Veterans Affairs $2 billion to $4 billion a year, depending on what you include in the calculation, and it’s also dangerous for the soldiers on the battlefield who can’t quickly identify where the enemy is coming from. Their communications also take place in high background-noise levels, which is specifically what noise-induced hearing loss starts to diminish, so it decreases the safety of the crew out on the battlefield. It’s the most common reason why soldiers cannot be redeployed, and it’s the most common disability in the military.

“Hearing loss is dangerous for the soldier on the battlefield who can’t quickly identify where the enemy is coming from.”

Most adult hearing loss is at high frequencies, more than low frequencies, which is exactly where the consonant sounds are. That’s why people with high-frequency hearing loss that is either noise- or drug-induced will say, “I can hear, but I can’t understand.” So people want to shout at them, which actually makes it worse, because when you shout, the vowels get louder but the consonants do not. You’re overwhelming their ear with the sounds they could already hear clearly, and then, relatively speaking, your consonants are heard even less. So shouting doesn’t help. What does help them is to be able to watch your face. But background noise is a real problem for soldiers, and sometimes they’re not able to see others’ faces. The best thing would be to prevent it in the first place.
In addition to blasts and gunfire, what else do soldiers encounter that can damage their hearing?
Soldiers have varying and relatively frequent noise exposures. If you are out on a carrier, your noise levels are constant—24/7—and they’re frequently in the background. If soldiers are deployed to, say, Iraq, there are background-noise generators because they have to have power sources, and they’re noisy. The trucks, the heavy equipment. But yes, the M-16 weapons they use peak at 155 decibels. Carriers can be 120 decibels. And hearing IEDs or grenades detonating is also blast exposure.
How did you arrange the study with the military?
One of the military audiologists from Fort Jackson, Maj. Jillyen Curry-Mathis, who was in charge of its hearing program, was at a lecture of mine where I was talking about the clinical-trials populations I needed to test how well D-met works in humans. I was really hoping for weapons training because that’s where they have a lot of uniform noise exposure in a short period of time. She came up after the lecture and said, “I think I can help you, ma’am.” Then we needed a number of approvals, and I went down to Fort Jackson to meet with the colonel in charge of the base’s weapons training. We went through all the different populations—they do over 63,000 weapons trainings a year at Fort Jackson—and we decided to go with the drill-sergeant instructor training school. Then we had to get permission and support, and it took a long time to get it set up, but people were certainly supportive and interested because they know what a problem this is for the military from a number of perspectives: financial impact, career impact and, of course, human impact.
How is the study set up?
These soldiers are drill-sergeant-instructor trainees, so they’re model soldiers—the cream of the crop. And it’s totally voluntary. There’s no pressure whatsoever. The study and the informed consent process are explained to them—no one in uniform or who supervises them can participate in the recruitment process, just to ensure they don’t feel obligated. There are military ombudsmen there who are nonmilitary people but who supervise the whole process to ensure that everything goes according to the IRB [institutional review board] rules and regulations for human-subjects’ protection. The soldiers are then screened, and if they are eligible and choose to participate, they start either D-met or a placebo. It’s a double-blind, randomized controlled trial, so nobody knows whether they’re getting a placebo or D-met. It’s an orange-flavored liquid.
They take it twice a day, starting three days before the noise exposure, and continue it twice a day during their M-16 weapon training, where they fire 500 rounds in 11 days. And then they continue another four days after. According to our preclinical data, they probably won’t need to take it that long to get an effect, but we’re maximizing our chances of seeing an effect at this point in time. We do a hearing test at baseline, and then we do another hearing test two weeks after their training ends. They have to have a quiet period for a couple of weeks, without training or loud noise exposure, so that when we measure the final hearing we know that it’s stabilized and it’s not being affected by a recent noise exposure with temporary threshold shift.

“One of the interesting things we saw in our preclinical work is that we can first administer the D-met 24 hours after a noise exposure to reverse the hearing back—and prevent permanent hearing loss.”

When did you begin the study and how long will it run?
We started collecting data in October 2013, when we did a small run to make sure all the systems were working properly for data collection, data storage, et cetera. Then we went more full scale in January 2014. It took us more than two years to get all the approvals in place—going through the Food and Drug Administration (FDA), the IRB, military approval—so that was a very long process. We are powered for 600 total subjects, and based on current recruitment, which has been increasing, we expect study completion by the end of 2016.
Sometimes the effects of noise-induced hearing loss may not show up for a couple years. Does the study take that into consideration?
In this cohort, we cannot look at long-term changes. It’s simply not possible. Within the military when we look at populations, you simply can’t do it. Also, you would not be able to rule out the effects of other noise exposures they’ve had in intervening years. So that’s why we chose this population; they should be seeing some permanent threshold shift or early-warning permanent threshold shift within the timeframe of the study’s hearing tests, and that’s a pretty good indication of whether or not they have damage.
Keep in mind, they’re still wearing their physical hearing protectors, and every [military] hearing conservation program effort is being made to conserve their hearing during this time. So they’re still wearing top-level hearing protectors, with all the compliance checks for using their hearing protection. But with this level of noise exposure, it can exceed the capability of physical hearing protectors to fully protect them.
Have you been involved in other areas of hearing conservation in the military?
I’ve been involved with the DoD’s Hearing Center of Excellence, which serves all branches of the military to try to reduce hearing loss. It was formed after the military really started looking at the number of people who were impacted by noise-induced hearing loss and tinnitus and the many costs that come with that. I’m mostly involved with what’s called the PIHL group—Pharmaceutical Intervention for Hearing Loss. We’re trying to develop new drugs to prevent noise-induced hearing loss, but there’s another component to the HCE that specifically looks at physical hearing protectors, which are called HPDs—hearing protection devices.
If the study shows that the drug works and it gets approved by the FDA, how could it also affect the civilian world?
We’re working with the military because that’s our prime concern right now. I have relatives who have served in the military—my brother-in-law and sister-in-law are both disabled army veterans. Another brother-in-law also served, but fortunately he was not injured during his service. My dad was in the Navy. So I certainly want to develop this for the military.
But as we know, noise-induced hearing loss is the most common cause of hearing loss worldwide, so would there be other applications? Absolutely. I would like it very much that if you or I go to a concert, and it’s unexpectedly loud, and we walk out and our hearing is muffled, we could stop by the pharmacy, or our physician, and get something to reverse that. One of the interesting things we saw in our preclinical work—though we’re not testing it in our current trial—is that we can first administer the D-met 24 hours after a noise exposure to reverse the hearing back—which is called “rescue therapy”—and prevent permanent hearing loss. That would be huge.
Are there any other current studies specifically working with a military population with a drug for noise-induced hearing loss?
There are no other clinical trials within the military right now, but there are other drugs that are under study. We’re the only one funded by the DoD and conducting clinical trials within it. Acetylcysteine was tested at Camp Pendleton [in California] some years ago, but the clinical trial study just came out this year and it didn’t work.
What’s next for D-met?
We have a new grant from NIH to help explore rescue dosing and look at biomarkers for dosing—a lot more work on mechanisms. I’m also in the process of starting up a new biotech company, called MetArmor, so I’ll be reducing hours at the medical school. You cannot get a new drug approved without a commercial partner that’s going to market and distribute that drug. You can’t even apply because the FDA and the DoD say you may be wasting your time; if you got a drug approved and then nobody will market and distribute it, it’s still not available to patients. Currently there is no drug approved by the FDA for any form of hearing loss or tinnitus, so trying to get the companies to move it forward can be a little tricky. So I’m in the process of partnering to form this new little biotech company to get D-met over the finish line so we can make it available to patients.
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January 2016
Volume 21, Issue 1