Treating Tinnitus Using the Neuromonics Tinnitus Treatment Program: A Randomized, Double-blind Study

BACKGROUND AND SIGNIFICANCE

Tinnitus, defined as the perception of sound when no corresponding external auditory
stimulus exists, is a debilitating condition that is widespread yet difficult to
successfully treat. It is estimated that between 10% and 15% of the adult population
experience tinnitus to some degree. Although many people with tinnitus are not disturbed by
the sensation, the condition is disabling in 0.5% to 2% of the tinnitus population or
between 1.4 and 5 million people (Bauer & Brozoski, 2006). Additionally, tinnitus is among
the most prevalent of service-connected disabilities for veterans receiving compensation
according to the VA 2010 Annual Benefits Report, impacting over half a million veterans (US
Department of Veterans Affairs, 2010).

The impact of tinnitus on a patient's quality of life can be devastating (Tyler & Baker,
1983). Many patients report that the intrusive perception of sound - such as ringing,
roaring, or buzzing - interferes with their ability to relax, sleep and concentrate,
especially in quiet situations. Many tinnitus patients also report reduced tolerance of loud
sounds, and will tend to avoid noisy (e.g. social) situations. The disturbing effects of the
condition can lead to a desperate sense of loss of control.

Until recently, there has been no treatment that has been clinically validated as
consistently effective. Despite advances in understanding of the tinnitus condition, such as
the Neurophysiological Model (Jastreboff & Hazell, 1993), the promise of much improved
outcomes from treatment has yet to be realized in general clinical practice. Previously
available treatment options continue to be limited by a lack of clinically consistent
efficacy, efficiency, and/or user acceptability. Even Tinnitus Retraining Therapy (TRT), the
most widely advocated practical application of the principles of the Neurophysiological
Model, has been recently reported to yield only modest outcomes, and to require an extended
period of time (up to 24 months) to achieve these outcomes for a high proportion of patients
(J. A. Henry et al., 2005). Notably, some reports (Dineen, Doyle, Bench, & Perry, 1999;
Hiller & Haerkotter, 2005; McKinney, Hazell, & Graham, 1999; Schmitt & Kroner-Herwig, 2002;
Tyler, 2004) have questioned whether the acoustic stimulation used in tinnitus management
programs such as TRT, predominantly consisting of broadband noise generators or hearing
aids, provides any real incremental benefit over the counseling component of the program.

Furthermore, hearing aids and noise generators have been shown to provide limited clinical
benefits when used in tinnitus management programs (Hiller & Haerkotter, 2005; Moffat et
al., 2009), and these technologies are further limited by problems with user acceptability.
Many tinnitus sufferers report that they find hearing aids intolerable to wear due to their
decreased sound tolerance together with the unpredictability of amplified ambient sounds.
Similarly, many people fitted with noise generators find the sound they produce unpleasant
to listen to for the extended periods each day for which their use is recommended. As a
result, for both hearing aids and noise generators, return-for-credit and
"left-unused-in-the-drawer" rates are very high (J.A. Henry, Schecthter, Nagler, & Fausti,
2002; Hiller & Haerkotter, 2005).

Recent research into the pathogenesis of tinnitus has emphasized the role of neurological
changes that result from damage to the auditory system (Tyler, 2005). These changes include
the brain's adaptive response to auditory starvation (leading to increased sensitivity in
the system), the initial perception of sound, and the systems within the brain that
determine the person's attention and reaction to it.

The Neuromonics Tinnitus Treatment Program (NTTP) takes into account the neural plasticity
that underlies tinnitus and targets the neurological changes that cause it. It utilizes an
acoustic stimulus that combines music with an embedded neural stimulus, which are spectrally
modified and customized for each patient's hearing and tinnitus profile. By accounting for a
patient's hearing loss, the NTTP provides a broadband neural stimulus to stimulate the
neural pathways that are "starved" due to auditory damage and/or hearing loss. The NTTP
stimulus also positively engages the limbic system to reduce the stress caused by the
tinnitus.

A key benefit of the customization process is that it allows the stimulus to be used at a
comfortably low listening level. By allowing for intermittent, momentary perception of the
tinnitus within a pleasant and relaxing listening experience, it desensitizes the patient's
reaction to the tinnitus, thereby leading to long-term reduction in tinnitus disturbance.

The NTTP has been clinically proven in civilian populations to : (1) reduce symptoms early
in treatment, in particular, provide relief from the disturbing effects of the condition,
(2) treat the neurological causes associated with tinnitus, (3) provide long-term relief and
improvements in quality of life, and (4) be convenient and noninvasive.

The NTTP has been the subject of a series of published clinical studies with civilian
subjects (P. B. Davis, 2005; P. B. Davis, Paki, & Hanley, 2007; P.B. Davis, Wilde, & Steed,
2002; P. B. Davis, Wilde, Steed, & Hanley, 2008; Hanley, Davis, Paki, Quinn, & Bellekom,
2008), which have demonstrated that it yields better results, more quickly, more
consistently, and with an intervention that is more acceptable to the patient than prior
approaches. Included among these clinical studies was a comparative study (P. B. Davis et
al., 2008) that showed that the Neuromonics Tinnitus Treatment generates significantly
greater and more consistent improvements in tinnitus symptoms than a treatment comprised of
counseling plus broad band noise ('white noise') and better outcomes than counseling-alone.

While the efficacy of the NTTP has been demonstrated, it remains an expensive and somewhat
time-consuming treatment strategy. A previous study (Karch, Hill, Casto, Nedostup, & Staton,
2014) indicated that a COTS sound therapy may also be an effective way to treat tinnitus.
Preliminary analysis of subjective tinnitus measures from Karch (2014) indicates that the
NTTP strategies were effective at reducing the negative effects of tinnitus (i.e. reduction
in subjective effects of tinnitus as measured by the Tinnitus Reaction Questionnaire (TRQ),
tinnitus awareness time, and tinnitus disturbance time). Similar results were seen with a
COTS group, with statistically significant differences in pre- and post-treatment measures
of TRQ and tinnitus awareness. Analysis of clinical measures associated with tinnitus
suggest no differences between pre- and post-treatment on the masking level required to
cover tinnitus or the level of loudness discomfort associated with tinnitus for either
group. However, due to the small sample size and unequal groups, comparisons between the
treatments in the Karch et al. study (2014) should be made cautiously.

MILITARY RELEVANCE

Tinnitus is among the most prevalent medical complaints soldiers have when returning from
Operation Iraqi Freedom/ Operation Enduring Freedom (OIF/OEF). Soldiers with clinically
significant levels of tinnitus often suffer from anxiety, depression, sleep disruption, and
difficulty concentrating. Currently, there is no standard tinnitus treatment protocol in the
military system and limited clinical efficacy on the NTTP and COTS tinnitus treatment
supported by a controlled study. The proposed research will attempt to definitively
establish the value of the NTTP in a military setting.

The study stresses the return-to-duty of Soldiers experiencing severe tinnitus that might
otherwise prevent these Soldiers from deploying with their units. Retention of a fit force
and improved quality of life for active-duty Soldiers are important issues associated with a
successful approach to the treatment of tinnitus.

OBJECTIVES/SPECIFIC AIMS/RESEARCH QUESTIONS

The objective of the study is to determine the effectiveness of individualized sound stimuli
used in a FDA classified tinnitus masker device, the Neuromonics, Inc. Oasis™.

Research Question: Is there a difference in clinical outcomes for tinnitus patients treated
with the NTTP compared with the same treatment using a placebo-control device? The
placebo-control device is otherwise identical to the NTTP device except that the sound
stimuli are not matched to the patients' audiograms and tinnitus profile and are not
specifically designed to promote relaxation. Assignment of tinnitus patients to the
treatment and placebo groups is performed off site and the experimenters have no information
on group assignment.

Hypothesis: In the Active Duty, Reserve, and National Guard military and recently separated
veteran populations with complaints of tinnitus, the NTTP group will have significantly
improved tinnitus clinical outcomes in comparison to placebo-control group at 6 months.
Clinical outcomes are described in Section B5.4 and Table 1 below.

Null Hypothesis: In the Active Duty, Reserve, and National Guard military and recently
separated veteran populations with complaints of tinnitus, the NTTP group will have tinnitus
clinical outcomes statistically indistinguishable from the placebo-control group at 6
months.

Inclusion Criteria:

- If an active duty military personnel, must be between the ages of 18 to 60 years at
the time of enrollment.

- If a veteran, must be between the ages of 19 to 60 years at the time of enrollment

- Tinnitus disturbance determined at the initial pre-enrollment assessment to be
clinically significant, as denoted by a score on the TRQ of 17-70; and

- Four frequency (0.5, 1, 2, and 4 kHz) pure tone average in one ear (0.5, 1, 2, and 4
kHz) is equal to or less than 50dB HL, as determined by audiometry performed at the
initial pre-enrollment assessment; and

- Cognitive, comprehension and manual dexterity abilities sufficient to self-administer
treatment, and ability to travel to attend appointments, as necessary, as determined
at the initial pre-enrollment assessment; and

- Motivated to pursue treatment and has appropriate expectations as to treatment
outcomes (including the possibility of being assigned to the placebo group), as
determined at the initial pre-enrollment assessment.

- Must have access to healthcare for follow-up care for the six month study period

Exclusion Criteria:

- Refusal to give consent

- Significant psychological disturbance [defined as any rating other than 0 on Question
Number 24 the TRQ (suicidal ideology) or a score of more than 78 on the Tinnitus
Handicap Inventory (THI)] that may interfere with the treatment as assessed by the
treating clinician and/or referring physician;

- Complicating medical conditions such as acute/unstable Meniere's disease as inferred
by responses on the Tinnitus History Questionnaire (THQ);

- Ongoing use of ototoxic medications (THQ);

- Pulsatile tinnitus (THQ);

- Continued excessive noise exposure without effective hearing protection (THQ);

- After all elements of informed consent are completed and the TRQ has been scored, a
score of less than 17 will exclude the volunteer from participation.