TNF-α Treatment of Blast-Induced Tinnitus

Overview

This study evaluates the therapeutic effects of Etanercept (Enbrel) on the treatment of blast/noise induced tinnitus in adults. Half of the participants will receive 2 x 25mg/ Entanercept injections, and the other half will receive placebo injections.

Description

The primary objectives are to test if: 1) Etanercept significantly reduces tinnitus distress as measured by Tinnitus Functional Index (TFI); and 2) Etanercept improves hearing. In addition, the investigators will test if: 1) Etanercept treatment leads to sustained therapeutic effects over time;

The secondary objective is to test if: 1) Etanercept reduces tinnitus loudness measured by visual numeric scale (VNS) rating.

Eligibility

Inclusion Criteria:

1. Tinnitus of at least a moderate severity as defined by a score of ≥ 25 points or higher on the Tinnitus Functional Index (TFI) questionnaire associated with one or more of the following:
   1. Blast or noise exposure
   2. Traumatic brain injury (TBI) and/or concussion diagnosed by a health care provider.
2. Able to provide written informed consent.
3. Age: Minimum 18 years of age at the time of enrollment.
4. Other concurrent treatments: A four-week washout from any other tinnitus treatment or management program is required prior to entering this study.
5. Psychological status: Stable enough to complete this study per the opinion of the research team.
6. Hearing function: All degrees of hearing function can be included, recognizing that individuals with profound, bilateral hearing loss will not be able to perform tinnitus evaluations and hearing tests but will be able to rate subjective tinnitus loudness, annoyance and impact on life. This is an important sub-population because of the challenges in treating them with acoustic therapy and the need for a medical intervention.
7. Additional tinnitus characteristics:
   1. Tinnitus history: Onset associated with blast and/or noise exposure or associated with diagnosed TBI and/or concussion. Subjects will have blast exposure, noise exposure, traumatic brain injury (TBI), and/or concussion impact, defined as exposure/impact less than or longer than six months at time of enrollment.

             (i) Participants enrolled with tinnitus associated with TBI and/or concussion must
             have received a diagnosis of TBI and/or concussion by a health care provider.
             b) Stability: Constant (not pulsatile, intermittent, varying to a high degree in
             loudness or changing in location of perception). Fluctuating tinnitus reduces the
             reliability of test-retest measures for loudness.
             c) Location of tinnitus perception: Unrestricted. Tinnitus may be unilateral,
             bilateral, or perceived in the head.
        Exclusion Criteria:
          1. History or evidence of significant brain malformation, cerebral vascular events (such
             as strokes), neurodegenerative disorders affecting the brain (such as Parkinson's
             disease, ALS, Huntington's disease or Multiple sclerosis), or prior brain surgery.
          2. History of Guillain-Barré syndrome.
          3. Active neoplasm such as lymphoma or solid tumors.
          4. History of neoplasm, excluding successfully treated squamous cell carcinoma or basal
             carcinoma of the skin or cervical cancer.
          5. Diagnosis of congestive heart failure.
          6. History of seizures or epileptic activity.
          7. Subjects with cardiac pace makers, other electronic implants (including cochlear
             implants), or intracranial or intraocular metallic particles.
          8. Subjects who currently have an active infection, including tuberculosis, HIV,
             hepatitis B, and/or chicken pox.
          9. Scheduled to receive a live vaccine during study participation or received a live
             vaccine within 2 weeks prior to screening visit/procedures.
         10. Diagnosis of active neurologic disease, auto-immune disease, diabetes, or a weak
             immune system.
               1. For the purposes of this protocol, "active neurologic disease" is defined as
                  multiple sclerosis or any other disease involving demyelination disorder or any
                  finding suggesting a demyelination disease or disorder. Migraines/migraine
                  headaches are not a condition that would exclude a potential patient from
                  participation in the study unless associated with a demyelination disease or
                  disorder.
               2. Autoimmune thyroid disease is not considered an exclusionary autoimmune disease
                  for participation in this study.
         11. Ongoing treatment with one of the following contraindicated medications: abatacept or
             any other biologic therapy, cyclophosphamide or sulfasalazine.
         12. Subjects who cannot communicate reliably with research team members or who are not
             likely to cope with the requirements of the trial.
         13. Subjects who have participated in a drug clinical trial within the last 30 days before
             the start of this one.
         14. Current substance abuse (defined as a score of 2 or greater on the CAGE Substance
             Abuse Screening Tool).
         15. Pregnancy or planned pregnancy during the study.
         16. Women who are lactating or are of child-bearing-age without use of contraception.
         17. Participation in greater than two previous clinical drug-trials for tinnitus.
         18. MMSE score < 24.
         19. Clinically significant out of range laboratory values (contact medical monitor to
             discuss).