Etanercept for Tinnitus

Recruiting at 9 trial locations

Overseen By Robert Hong, MD/Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wayne State University

Must not be taking: Immunomodulatory biologics, Cyclophosphamide, Sulfonylureas, others

Disqualifiers: Diabetes, Seizure disorder, Auto-immune disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 12 weeks

88 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Etanercept, a TNF receptor fusion protein, can reduce the severity of tinnitus, the constant ringing in the ears. The study compares Etanercept with a placebo to determine its effectiveness. Individuals with persistent tinnitus from loud noise exposure, past traumatic brain injury (TBI), or concussion might be suitable candidates. Participants will receive weekly injections for 12 weeks while maintaining their daily routines. As a Phase 2 trial, this research aims to measure the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires a four-week period without any other tinnitus treatments before starting. Some medications, like cyclophosphamide, sulfasalazine, and certain diabetes and immunomodulatory drugs, are not allowed during the study.

Is there any evidence suggesting that Etanercept is likely to be safe for humans?

Research shows that Etanercept is generally safe, with some minor side effects. The most common issues include injection site reactions and mild colds. Studies have found that Etanercept is usually well-tolerated for other conditions. However, the FDA has not approved Etanercept for treating tinnitus. In one study with tinnitus patients, some felt better, while others saw no change or felt worse. This indicates that while there is potential, effects can vary among individuals. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for tinnitus?

Unlike the standard treatments for tinnitus, which typically include sound therapy and cognitive behavioral therapy, etanercept offers a unique approach by targeting inflammation. Etanercept is a biologic that acts as a TNF inhibitor, potentially reducing inflammation in the auditory pathways that might contribute to tinnitus. Researchers are excited about etanercept because, if effective, it could provide relief in a way that directly addresses an underlying biological process, rather than just managing symptoms. This makes it a promising candidate for offering patients a new avenue of relief.

What evidence suggests that Etanercept might be an effective treatment for tinnitus?

Research has shown that Etanercept, which participants in this trial may receive, might lessen the severity of tinnitus, particularly when caused by loud noise or traumatic brain injuries (TBI). Some patients experienced improvements in ear-related conditions after Etanercept treatment. This treatment reduces inflammation, which might contribute to tinnitus. Although the findings are not yet definitive, early results suggest it could relieve those with ongoing ringing in their ears due to noise exposure or TBI. ^{1 3 4 6 7}

Who Is on the Research Team?

Jinsheng Zhang, Ph.D.

Principal Investigator

Wayne State University

Are You a Good Fit for This Trial?

Adults with moderate to severe tinnitus from noise or blast exposure, or associated with traumatic brain injury (TBI) or concussion. Participants must be stable enough psychologically for the study, not have used other tinnitus treatments in the last four weeks, and able to consent. All hearing levels are included but those with profound loss can't do certain tests.

Inclusion Criteria

Able to provide written informed consent.

People with any level of hearing ability can join the study. However, individuals with severe hearing loss won't be able to do certain hearing tests.

Able to provide written informed consent

Exclusion Criteria

I am not currently taking abatacept, cyclophosphamide, sulfasalazine, or similar medications.

You currently have a problem with drugs or alcohol.

I am a woman of child-bearing age not using contraception or I am breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Etanercept or placebo injections weekly

12 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Exploratory

Exploratory investigations to identify factors influencing therapeutic effects

36 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Etanercept

Trial Overview The trial is testing Etanercept (Enbrel), a medication given through injections, against a placebo (saline solution). The goal is to see if Etanercept can reduce the severity of tinnitus caused by loud noises or blasts. Participants will be randomly assigned to receive either Etanercept or placebo.

How Is the Trial Designed?

Group I: Etanercept Injection Group Experimental Treatment 1 Intervention

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

Group II: Placebo Injection Group Placebo Group 1 Intervention

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

Etanercept is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Enbrel for:

• Moderate to Severe Rheumatoid Arthritis
• Moderate to Severe Polyarticular Juvenile Rheumatoid Arthritis
• Psoriatic Arthritis
• Ankylosing Spondylitis
• Moderate to Severe Plaque Psoriasis

Approved in European Union as Enbrel for:

• Rheumatoid Arthritis
• Juvenile Idiopathic Arthritis
• Psoriatic Arthritis
• Ankylosing Spondylitis
• Plaque Psoriasis

Approved in Canada as Enbrel for:

• Rheumatoid Arthritis
• Juvenile Idiopathic Arthritis
• Psoriatic Arthritis
• Ankylosing Spondylitis
• Plaque Psoriasis

Who Is Running the Clinical Trial?

Wayne State University

Lead Sponsor

Trials

318

Recruited

111,000+

University of Iowa

Collaborator

Trials

486

Recruited

934,000+

United States Naval Medical Center, San Diego

Collaborator

Trials

110

Recruited

24,200+

University of Miami

Collaborator

Trials

976

Recruited

423,000+

Michigan Ear Institute

Collaborator

Trials

1

Recruited

90+

Madigan Army Medical Center

Collaborator

Trials

52

Recruited

17,600+

Portland VA Medical Center

Collaborator

Trials

44

Recruited

7,800+

Published Research Related to This Trial

Etanercept is a fusion protein that acts as a soluble receptor for tumor necrosis factor (TNF), effectively used to treat various chronic inflammatory diseases in humans, such as rheumatoid arthritis and psoriasis.

To study its effects in mouse models, researchers developed a murine version of the soluble p75-TNF receptor, allowing for better understanding of its mechanism in conditions that mimic human granulomatous infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Construction and purification of the murine p75-murine IgG1 fusion protein. Kim, HY., Renshaw-Gegg, LW., Balciunas, AM., et al.[2016]

Etanercept has shown preliminary effectiveness in treating methotrexate-resistant polyarticular juvenile idiopathic arthritis (JIA), suggesting it could be a valuable option for patients who do not respond to standard treatments.

While most side effects of etanercept have been minor, two patients experienced a urticaria-like rash after injections, indicating that while generally safe, some individuals may have specific adverse reactions that need monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etanercept and urticaria in patients with juvenile idiopathic arthritis. Skyttä, E., Pohjankoski, H., Savolainen, A.[2017]

In a randomized, double-blind, placebo-controlled trial involving 234 patients with active rheumatoid arthritis, etanercept demonstrated significant improvements in disease activity over 6 months, with 59% of patients achieving a 20% improvement compared to only 11% in the placebo group.

Etanercept was well tolerated and showed a dose-dependent effect, with no dose-limiting toxic effects, confirming its safety and efficacy as a treatment for rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Moreland, LW., Schiff, MH., Baumgartner, SW., et al.[2022]

Murine p75-Fc, a soluble TNF receptor protein, effectively inhibits TNF-induced IL-6 production in mice, with complete inhibition observed at doses of 5 and 15 mg/kg.

At a lower dose of 1.5 mg/kg, murine p75-Fc still significantly reduced IL-6 production, indicating its potential as a therapeutic agent in managing inflammatory responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamic effects of the murine p75-Fc fusion protein in mice. Hu, YL., Kim, HY., Kohno, T., et al.[2016]

In a study of 43 patients with moderate to severe Crohn's disease, etanercept did not show significant efficacy compared to placebo, with only 39% of patients responding to treatment at week 4.

The safety profile of etanercept was similar to that of placebo, indicating that while it is safe to use, higher doses or more frequent administration may be necessary to achieve a therapeutic effect in Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etanercept for active Crohn's disease: a randomized, double-blind, placebo-controlled trial. Sandborn, WJ., Hanauer, SB., Katz, S., et al.[2022]

Etanercept is an effective and safe treatment for rheumatoid arthritis (RA), significantly reducing disease activity and preventing joint damage, and can be used alone or with methotrexate for enhanced effectiveness.

While generally safe, etanercept requires caution due to potential risks such as re-activating tuberculosis and concerns about lymphoma, and it is recommended for patients who have not responded to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etanercept in arthritis. Scott, DL.[2015]

Preliminary reports suggest that etanercept does not increase morbidity or mortality in patients with HIV, indicating it may be a safe option for managing symptoms associated with HIV/AIDS.

Etanercept may help alleviate symptoms such as aphthous ulcers, cachexia, and fatigue in HIV/AIDS patients, while also managing related rheumatic diseases, but further research is needed to confirm its long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of etanercept in human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients. Ting, PT., Koo, JY.[2015]

In a study involving 12 patients with occupational medicamentosa-like dermatitis, treatment with etanercept significantly reduced the severity of the condition, as indicated by a decrease in the Drug Eruption Area and Severity Index (DASI) score from 56.33 to 0.50 after 4 weeks (P<0.01).

All patients achieved at least a 50% reduction in DASI score, and there were no reported adverse reactions, suggesting that etanercept is both effective and safe for treating this specific dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Recombinant human tumor necrosis factor receptor type Ⅱ-IgG Fc fusion protein for treatment of occupational medicamentosa-like dermatitis induced by trichloroethylene]. Lv, LL., Yan, ZH., Shi, X., et al.[2019]

Citations

1. adventhealth.com adventhealth.com/medical/adventhealthmd/news/adventhealth-research-institute-offers-phase-ii-clinical-trial-etanercept-treatment-blast-induced

AdventHealth Research Institute Offers Phase II Clinical ... The purpose of this research study is to determine if etanercept, compared to a placebo, significantly reduces the severity of tinnitus (ringing in the ears)

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/11568668/

Etanercept therapy for immune-mediated cochleovestibular ... The condition of one patient improved dramatically at first but deteriorated after 5 months. The patient's hearing was rescued and stabilized with the addition ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04066348

NCT04066348 | TNF-α 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 ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04066348/tnf-a-treatment-of-blast-induced-tinnitus

TNF-α 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.

5. withpower.com withpower.com/trial/phase-3-tinnitus-6-2021-925a0

Etanercept for Tinnitus · Recruiting Participants for Phase ... This trial tests if Etanercept injections can help adults with noise-induced tinnitus by reducing inflammation. The study aims to see if it can lower tinnitus ...

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/48/NCT04066348/ICF_003.pdf

Clinical Trial of Etanercept (TNF-α Blocker) for Treatment of ... The FDA has not approved Etanercept for the treatment of tinnitus; therefore, the use of this medication for treatment of tinnitus in this study is considered ...

7. acrjournals.onlinelibrary.wiley.com acrjournals.onlinelibrary.wiley.com/doi/abs/10.1002/art.21179

Etanercept therapy for immune‐mediated cochleovestibular ... Of 21 patients with tinnitus, this symptom improved in 7 (33%), was unchanged in 10 (48%), and worsened in 3 (13%). Of 16 patients with vertigo, ...