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 if Etanercept injections can help adults with noise-induced tinnitus by reducing inflammation. The study aims to see if it can lower tinnitus distress and loudness, and improve hearing.

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 Etanercept generally safe for humans?

Etanercept has been shown to be generally safe in humans, with minor side effects like injection site reactions and upper respiratory infections. However, caution is advised as it may reactivate tuberculosis and there are concerns about a potential link to lymphoma. ^{1 2 3 4 5}

How does the drug Etanercept differ from other treatments for tinnitus?

Etanercept is unique because it is a fusion protein that targets and binds to tumor necrosis factor-alpha (TNF-alpha), a molecule involved in inflammation, which is not a common approach for treating tinnitus. It is typically used for inflammatory conditions like rheumatoid arthritis, and its use for tinnitus is novel, as there are no standard treatments specifically targeting TNF-alpha for this condition. ^{2 3 4 5 6}

What data supports the effectiveness of the drug Etanercept for treating tinnitus?

Etanercept has been shown to be effective in reducing inflammation in conditions like rheumatoid arthritis and psoriatic arthritis by blocking a protein called TNF-alpha, which is involved in inflammation. While there is no direct evidence for tinnitus, its success in other inflammatory conditions suggests potential benefits. ^{3 4 5 7 8}

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

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Etanercept for active Crohn's disease: a randomized, double-blind, placebo-controlled trial. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Construction and purification of the murine p75-murine IgG1 fusion protein. [2016]

3. China 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]. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. [2022]

5. India pubmed.ncbi.nlm.nih.gov

Etanercept in arthritis. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Pharmacodynamic effects of the murine p75-Fc fusion protein in mice. [2016]

7. Italy pubmed.ncbi.nlm.nih.gov

Etanercept and urticaria in patients with juvenile idiopathic arthritis. [2017]

8. England pubmed.ncbi.nlm.nih.gov

Use of etanercept in human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients. [2015]