TNF-α Treatment of Blast-Induced Tinnitus

February 19, 2026 updated by: Dr. Jinsheng Zhang, Wayne State University

Clinical Trial of Etanercept (TNF-α Blocker) for Treatment of Blast-Induced Tinnitus

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

88

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Florida
      • Celebration, Florida, United States, 34747
      • Coral Gables, Florida, United States, 33124
        • Recruiting
        • University of Miami
        • Principal Investigator:
          • Michael Hoffer, MD
        • Contact:
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Wayne State University
        • Principal Investigator:
          • Jinsheng Zhang, Ph.D.
        • Contact:
      • Farmington Hills, Michigan, United States, 48334
        • Recruiting
        • Michigan Ear Institute
        • Principal Investigator:
          • Robert Hong, MD/Ph.D.
        • Sub-Investigator:
          • Dennis Bojrab
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Etanercept Injection Group
Subjects will receive 2 X 25mg/ 1ml etanercept injection (experimental) weekly for 12 weeks.
Biological: Etanercept
To treat blast or noise induced tinnitus
Other Names:
  • Enbrel
Placebo Comparator: Placebo Injection Group
Subjects will receive 2 X 1ml saline injection (placebo) weekly for 12 weeks.
Other: Saline
Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tinnitus Functional Index (TFI)
Time Frame: 12 Weeks
Self-report questionnaire used to assess the severity and negative impact of tinnitus (tinnitus distress). It uses an 11 point Likert scale with higher scores indicating more severe tinnitus (For example, "How strong or loud was your tinnitus?", 0 (Not at all strong or loud)-10 (Extremely strong or loud).
12 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Audiometric testing
Time Frame: 12 Weeks
Pure tone air conduction (AC) testing; Pure tone bone conduction (BC) testing; Speech recognition threshold (SRT); Tympanometry; Word recognition testing
12 Weeks
Tinnitus Testing
Time Frame: 12 Weeks
Tinnitus loudness matching (1 kHz loudness-matching); Minimum Masking Levels (MMLs)
12 Weeks
Visual Numeric Rating Scale
Time Frame: 12 Weeks
Self-rated visual numeric scale that asks respondents to rate the loudness of their tinnitus on a scale from 0 (No Tinnitus) to 10 (Very Loud). Higher scores indicate louder/more severe tinnitus.
12 Weeks
Tinnitus Primary Function Questionnaire
Time Frame: 12 Weeks
Self-report questionnaire assessing primary activities impaired by tinnitus. The questionnaire uses a self report number scale (1-100) asking respondents to indicate their agreement with each statement on a scale from 0 (completely disagree) to 100 (completely agree). Higher scores indicate worse tinnitus/more functional impairment from tinnitus.
12 Weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exploratory Aim Identify contributing factors that influence the therapeutic effects of Etanercept on blast-induced tinnitus - Age
Time Frame: 36 weeks
Conduct exploratory investigations to if AGE influences the therapeutic effects of Etanercept on blast-induced tinnitus, and leads lead to subgrouping of subjects.
36 weeks
Exploratory Aim Identify contributing factors that influence the therapeutic effects of Etanercept on blast-induced tinnitus - Hearing sensitivity
Time Frame: 36 weeks
Conduct exploratory investigations to if "Hearing sensitivity" influences the therapeutic effects of Etanercept on blast-induced tinnitus, and leads lead to subgrouping of subjects.
36 weeks
Exploratory Aim Identify contributing factors that influence the therapeutic effects of Etanercept on blast-induced tinnitus - History of noise exposure, which can be captured with questionnaires
Time Frame: 36 weeks
Conduct exploratory investigations to if "History of noise exposure, which can be captured with questionnaires" influences the therapeutic effects of Etanercept on blast-induced tinnitus, and leads lead to subgrouping of subjects.
36 weeks
Exploratory Aim Identify contributing factors that influence the therapeutic effects of Etanercept on blast-induced tinnitus - Time since blast exposure (and number of blast exposures)
Time Frame: 36 weeks
Conduct exploratory investigations to if "Time since tinnitus started (tinnitus duration)" influences the therapeutic effects of Etanercept on blast-induced tinnitus, and leads lead to subgrouping of subjects.
36 weeks
Exploratory Aim Identify contributing factors that influence the therapeutic effects of Etanercept on blast-induced tinnitus - Time since military service ended
Time Frame: 36 weeks
Conduct exploratory investigations to if "Time since military service ended" influences the therapeutic effects of Etanercept on blast-induced tinnitus, and leads lead to subgrouping of subjects.
36 weeks
Exploratory Aim Identify contributing factors that influence the therapeutic effects of Etanercept on blast-induced tinnitus - History of traumatic brain injury (TBI)
Time Frame: 36 weeks
Conduct exploratory investigations to if "History of traumatic brain injury (TBI)" influences the therapeutic effects of Etanercept on blast-induced tinnitus, and leads lead to subgrouping of subjects.
36 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wayne State University

Collaborators

University of Miami
Michigan Ear Institute

Investigators

  • Principal Investigator: Jinsheng Zhang, Ph. D., Wayne State University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2022

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

September 1, 2026

Study Registration Dates

First Submitted

July 29, 2019

First Submitted That Met QC Criteria

August 20, 2019

First Posted (Actual)

August 26, 2019

Study Record Updates

Last Update Posted (Actual)

February 23, 2026

Last Update Submitted That Met QC Criteria

February 19, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PR172190

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

In cases where the human subject could possibly benefit medically or otherwise from the information, explain whether or not the results of screening and/or study participation will be shared with human subjects or their primary care provider, to include results from any screening or diagnostic tests performed as part of the study.

The PI plans to disseminate abstracts in National and International Conferences, and the PI plans to publish manuscripts in peer-reviewed journals (national and international) to share the knowledge obtained from the study's data with the research team of this study. Any research team member planning to disseminate results from this study needs the permission of the PI and must follow FDA guidelines.Additionally, data collected during the proposed study period will be shared with the NIH, the Department of Veterans Affairs, the National Science Foundation, and the Department of Health Human.

IPD Sharing Time Frame

Sharing will be available 6 months after the study has concluded and data analysis in completed.

IPD Sharing Access Criteria

To follow FDA and IRB guidelines, as well as obtain permission from the PI.

IPD Sharing Supporting Information Type

  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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