Clinical trial NCT04066348: TNF-α Treatment of Blast-Induced Tinnitus
Official title: Clinical Trial of Etanercept (TNF-α Blocker) for Treatment of Blast-Induced Tinnitus
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Tinnitus, Noise Induced
Keywords: tinnitus
etanercept
tinnitus function index
tinnitus primary function
audiological evaluation
Lead sponsor: Wayne State University
Sponsor class: OTHER
Collaborators: name: University of Miami
name: Michigan Ear Institute
First posted: 2019-08-26
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this multi-site research study is to determine if Etanercept, compared to a placebo, significantly reduces the severity of tinnitus (ringing in the ears) associated with history of blast and/or noise exposure or associated with Traumatic Brain Injury (TBI) and/or concussion. Individuals who qualify will be randomized into one of two groups: The group receiving the medication Etanercept or the group receiving a saline solution placebo.

Detailed 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 explore whether 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 criteria: 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 for tinnitus: A four-week washout from any other tinnitus 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.
5. 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.
6. Additional tinnitus characteristics:

   a) 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 or intermittent). c) Location of tinnitus perception: Unrestricted. Tinnitus may be unilateral, bilateral, or perceived in the head.

Exclusion Criteria:

1. History or evidence of any of the following: Significant brain malformation; cerebral vascular events (such as strokes); neurodegenerative disorders affecting the brain, such as Parkinson's disease, ALS, or Huntington's disease; multiple sclerosis, Guillain-Barré syndrome, or any other disease involving demyelination disorder or any finding suggesting a demyelination disease or disorder; prior brain surgery.

   a. The following surgical procedures are not exclusionary: Evacuation of subdural hematoma, insertion of intracranial pressure monitor device, craniectomy
2. Active malignant neoplasm such as lymphoma or solid tumors or history of malignant neoplasm, excluding successfully treated squamous cell carcinoma or basal carcinoma of 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 live vaccine within 2 weeks prior to screening visit/procedures.
8. Diagnosis of an auto-immune disease that, in the opinion of the investigator, would cause a weakened immune system.

   a) Autoimmune thyroid disease is not considered an exclusionary autoimmune disease for participation in this study.
9. Diabetes.
10. Ongoing treatment with or plans to begin taking any of the following contraindicated medications: Cyclophosphamide or sulfasalazine; abatacept, anakinra, or any other immunomodulatory biologic therapy; sulfonylureas, meglitinides, or insulin.
11. Subjects who cannot communicate reliably with research team members or who are not likely to be able to complete the requirements of the trial per the discretion of the investigator.
12. Subjects who have participated in a drug clinical trial within the last 30 days before 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 required laboratory tests as assessed by the investigator.

Primary outcomes:
measure: Tinnitus Functional Index (TFI)
timeFrame: 12 Weeks
Secondary outcomes:
measure: Audiometric testing
timeFrame: 12 Weeks
measure: Tinnitus Testing
timeFrame: 12 Weeks
measure: Visual Numeric Rating Scale
timeFrame: 12 Weeks
measure: Tinnitus Primary Function Questionnaire
timeFrame: 12 Weeks
Other outcomes:
Locations:
city: Coral Gables
country: United States
facility: University of Miami
state: Florida
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Farmington Hills
country: United States
facility: Michigan Ear Institute
state: Michigan
Study officials:
affiliation: Wayne State University
name: Jinsheng Zhang, Ph. D.
role: PRINCIPAL_INVESTIGATOR
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