TNF-α Treatment of Blast-Induced Tinnitus

Inclusion Criteria:

1. Tinnitus of at least a moderate severity as defined by a score of ≥ 25 points orhigher on the Tinnitus Functional Index (TFI) questionnaire associated with one ormore of the following:

2. Blast- or noise exposure

3. Traumatic brain injury (TBI) and/or concussion diagnosed by a health careprovider.

4. Able to provide written informed consent.

5. Age: Minimum 18 years of age at the time of enrollment.

6. Other concurrent treatments for tinnitus: A four-week washout from any othertinnitus treatment or management program is required prior to entering this study. a) Hearing aids are permitted if the participant has been wearing them for at least 4 weeks.

7. Hearing function: All degrees of hearing function can be included, recognizing thatindividuals with profound, bilateral hearing loss will not be able to performtinnitus evaluations and hearing tests but will be able to rate subjective tinnitusloudness, annoyance and impact on life. This is an important sub-population becauseof the challenges in treating them with acoustic therapy and the need for a medicalintervention.

8. Additional tinnitus characteristics: a) Tinnitus history: Onset associated with blast and/or noise exposure or associatedwith diagnosed TBI and/or concussion. Subjects will have blast exposure, noiseexposure, traumatic brain injury (TBI), and/or concussion impact, defined asexposure/impact less than or longer than six months at time of enrollment. i. Participants enrolled with tinnitus associated with TBI and/or concussion musthave received a diagnosis of TBI and/or concussion by a health care provider. b) Stability: Constant (not pulsatile or intermittent). c) Location of tinnitusperception: Unrestricted. Tinnitus may be unilateral, bilateral, or perceived in thehead.

Exclusion Criteria:

1. History or evidence of any of the following: Significant brain malformation;cerebral vascular events (such as strokes); neurodegenerative disorders affectingthe brain, such as Parkinson's disease, ALS, or Huntington's disease; multiplesclerosis, Guillain-Barré syndrome, or any other disease involving demyelinationdisorder or any finding suggesting a demyelination disease or disorder; prior brainsurgery. a. The following surgical procedures are not exclusionary: Evacuation of subduralhematoma, insertion of intracranial pressure monitor device, craniectomy

2. Active malignant neoplasm such as lymphoma or solid tumors or history of malignantneoplasm, excluding successfully treated squamous cell carcinoma or basal carcinomaof the skin or cervical cancer.

3. Diagnosis of congestive heart failure.

4. History of diagnosed seizure disorder or epilepsy.

5. Diagnosis of myelodysplastic syndrome or aplastic anemia, white blood cell count < 4000, or platelet count < 150,000.

6. Subjects who currently have an active infection, including tuberculosis, HIV,hepatitis B, and/or chicken pox. a. Patients with latent hepatitis B infection are also excluded from participation.

7. Scheduled to receive a live vaccine during study participation or received a livevaccine within 2 weeks prior to screening visit/procedures.

8. Diagnosis of an auto-immune disease that, in the opinion of the investigator, wouldcause a weakened immune system. a) Autoimmune thyroid disease is not considered an exclusionary autoimmune diseasefor participation in this study.

9. Diabetes.

10. Ongoing treatment with or plans to begin taking any of the following contraindicatedmedications: Cyclophosphamide or sulfasalazine; abatacept, anakinra, or any otherimmunomodulatory biologic therapy; sulfonylureas, meglitinides, or insulin.

11. Subjects who cannot communicate reliably with research team members or who are notlikely to be able to complete the requirements of the trial per the discretion ofthe investigator.

12. Subjects who have participated in a drug clinical trial within the last 30 daysbefore the start of this one.

13. Pregnancy or planned pregnancy during the study.

14. Women who are lactating or are of child-bearing-age without use of contraception.

15. MMSE score < 24.

16. Clinically significant out of range laboratory values for protocol requiredlaboratory tests as assessed by the investigator.