Treatment for tinnitus caused by blast or noise exposure

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

This study is testing if a medication called Etanercept can help reduce the ringing in the ears for people who have tinnitus from noise exposure or brain injuries.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 88 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Wayne State University (Academic / other)
• Drugs / interventions: Cyclophosphamide
• Locations: 4 sites (Celebration, Florida and 3 other locations)
• Trial ID: NCT04066348 on ClinicalTrials.gov

What this trial studies

This multi-site research aims to evaluate the effectiveness of Etanercept in reducing the severity of tinnitus associated with blast or noise exposure, as well as traumatic brain injury (TBI) or concussion. Participants will be randomly assigned to receive either Etanercept or a saline placebo. The primary objectives include measuring changes in tinnitus distress using the Tinnitus Functional Index (TFI) and assessing improvements in hearing. Additionally, the study will explore the sustainability of therapeutic effects over time and the impact on tinnitus loudness.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with moderate to severe tinnitus linked to blast or noise exposure or TBI/concussion.

Not a fit: Patients with profound, bilateral hearing loss who cannot perform tinnitus evaluations may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly alleviate tinnitus symptoms for individuals affected by blast or noise exposure.

How similar studies have performed: While the approach of using Etanercept for tinnitus is novel, similar studies targeting tinnitus with different interventions have shown varying degrees of success.

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.

Where this trial is running

Celebration, Florida and 3 other locations

• Advent Health — Celebration, Florida, United States (Recruiting)
• University of Miami — Coral Gables, Florida, United States (Recruiting)
• Wayne State University — Detroit, Michigan, United States (Recruiting)
• Michigan Ear Institute — Farmington Hills, Michigan, United States (Recruiting)

Study contacts

• Principal investigator: Jinsheng Zhang, Ph. D. — Wayne State University
• Study coordinator: Jamal Chehab

Conditions Tinnitus, Noise Induced; tinnitus; etanercept; tinnitus function index; tinnitus primary function; audiological evaluation