TNF-α Treatment of Blast-Induced Tinnitus

NCT04066348 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PR172190
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 4

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.

Conditions

Tinnitus, Noise Induced

Keywords

tinnitus; etanercept; tinnitus function index; tinnitus primary function; audiological evaluation

Outcome Measures

Primary Outcomes (1)

• Tinnitus Functional Index (TFI)

  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 Outcomes (4)

• Audiometric testing

  12 Weeks

• Tinnitus Testing

  12 Weeks

• Visual Numeric Rating Scale

  12 Weeks

• Tinnitus Primary Function Questionnaire

  12 Weeks

Study Arms (2)

Etanercept Injection Group

EXPERIMENTAL

Subjects will receive 2 X 25mg/ 1ml etanercept injection (experimental) weekly for 12 weeks.

Biological: Etanercept

Placebo Injection Group

PLACEBO COMPARATOR

Subjects will receive 2 X 1ml saline injection (placebo) weekly for 12 weeks.

Other: Saline

Interventions

Etanercept BIOLOGICAL

To treat blast or noise induced tinnitus

Also known as: Enbrel

Etanercept Injection Group

Saline OTHER

Placebo

Placebo Injection Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Blast- or noise exposure
• Traumatic brain injury (TBI) and/or concussion diagnosed by a health care provider.
• Able to provide written informed consent.
• Age: Minimum 18 years of age at the time of enrollment.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• Diagnosis of congestive heart failure.
• History of diagnosed seizure disorder or epilepsy.
• Diagnosis of myelodysplastic syndrome or aplastic anemia, white blood cell count \< 4000, or platelet count \< 150,000.
• 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.
• Scheduled to receive a live vaccine during study participation or received a live vaccine within 2 weeks prior to screening visit/procedures.
• Diagnosis of an auto-immune disease that, in the opinion of the investigator, would cause a weakened immune system.
• Diabetes.
• 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.
• 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.
• Subjects who have participated in a drug clinical trial within the last 30 days before the start of this one.
• Pregnancy or planned pregnancy during the study.
• Women who are lactating or are of child-bearing-age without use of contraception.

Sponsors & Collaborators

• University of Miami: collaborator
• Michigan Ear Institute: collaborator
• Wayne State University: lead

Study Sites (4)

Advent Health

Celebration, Florida, 34747, United States

RECRUITING

University of Miami

Coral Gables, Florida, 33124, United States

RECRUITING

Wayne State University

Detroit, Michigan, 48201, United States

RECRUITING

Michigan Ear Institute

Farmington Hills, Michigan, 48334, United States

RECRUITING

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MeSH Terms

Conditions

Tinnitus

Interventions

Etanercept; Sodium Chloride

Condition Hierarchy (Ancestors)

Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Jinsheng Zhang, Ph. D.

  Wayne State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jamal Chehab

CONTACT

313-577-5495; tinnitustrial@wayne.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: July 29, 2019
• First Posted: August 26, 2019
• Study Start: July 1, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 23, 2026

Record last verified: 2026-02

Locations

US (4)