Tinnitus, Noise InducedPhase 2NCT04066348
TNF-α Treatment of Blast-Induced Tinnitus
A Phase 2 study testing Etanercept and Saline in people with Tinnitus, Noise Induced, run by Wayne State University at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tinnitus, Noise Induced
- What is being tested?
- Etanercept and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 4 sitesUnited States
- Study dates
- 1 Jul 2022to Feb 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 12Show fewer
- 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:
- 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.
- 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.
- Stability: Constant (not pulsatile or intermittent). c) Location of tinnitus perception: Unrestricted. Tinnitus may be unilateral, bilateral, or perceived in the head.
Who cannot join
- 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.
- The following surgical procedures are not exclusionary: Evacuation of subdural hematoma, insertion of intracranial pressure monitor device, craniectomy
- 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.
Show all 19Show fewer
- Subjects who currently have an active infection, including tuberculosis, HIV, hepatitis B, and/or chicken pox.
- 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.
- Autoimmune thyroid disease is not considered an exclusionary autoimmune disease for participation in this study.
- 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.
- MMSE score < 24.
- Clinically significant out of range laboratory values for protocol required laboratory tests as assessed by the investigator.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Advent Health
Celebration, Florida, 34747
University of Miami
Coral Gables, Florida, 33124
Wayne State University
Detroit, Michigan, 48201
Michigan Ear Institute
Farmington Hills, Michigan, 48334
About this study
Official title: 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.
Read the 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.
- Conditions
- Tinnitus, Noise Induced
- Being tested
- Etanercept, Saline
- Keywords
- tinnitus, etanercept, tinnitus function index, tinnitus primary function, audiological evaluation
- Medical subject headings
- Tinnitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtanerceptBiological
Also called Enbrel
To treat blast or noise induced tinnitus
SalineOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Etanercept Injection Group | Experimental | Subjects will receive 2 X 25mg/ 1ml etanercept injection (experimental) weekly for 12 weeks. Receives: Biological: Etanercept |
| Placebo Injection Group | Placebo comparator | Subjects will receive 2 X 1ml saline injection (placebo) weekly for 12 weeks. Receives: Other: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 12 Weeks
Secondary outcomes (4)
Audiometric testing
Pure tone air conduction (AC) testing; Pure tone bone conduction (BC) testing; Speech recognition threshold (SRT); Tympanometry; Word recognition testing
Measured: 12 Weeks
Tinnitus Testing
Tinnitus loudness matching (1 kHz loudness-matching); Minimum Masking Levels (MMLs)
Measured: 12 Weeks
Visual Numeric Rating Scale
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.
Measured: 12 Weeks
Tinnitus Primary Function Questionnaire
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.
Measured: 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2019
- Study start1 Jul 2022
- Primary completionDec 2026 (estimated)
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (65)Papers the sponsor has linked to this study.
- Other trials for Tinnitus, Noise InducedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 88 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wayne State University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Miami, Michigan Ear Institute
- Responsible party
- Principal investigator, Dr. Jinsheng Zhang, Wayne State University
- Investigators
- Jinsheng Zhang, Ph. D., Principal investigator, Wayne State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04066348
- Sponsor's protocol ID
- PR172190
- Status last verified
- Oct 2026
- First submitted
- 29 Jul 2019
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Meikle MB, Henry JA, Griest SE, Stewart BJ, Abrams HB, McArdle R, Myers PJ, Newman CW, Sandridge S, Turk DC, Folmer RL, Frederick EJ, House JW, Jacobson GP, Kinney SE, Martin WH, Nagler SM, Reich GE, Searchfield G, Sweetow R, Vernon JA. The tinnitus functional index: development of a new clinical measure for chronic, intrusive tinnitus. Ear Hear. 2012 Mar-Apr;33(2):153-76. doi: 10.1097/AUD.0b013e31822f67c0.
PubMed 22156949Lew HL, Jerger JF, Guillory SB, Henry JA. Auditory dysfunction in traumatic brain injury. J Rehabil Res Dev. 2007;44(7):921-8. doi: 10.1682/jrrd.2007.09.0140.
PubMed 18075949VBA. VA Annual Benefits Report: Fiscal Year 2012. In: VA US, ed. 810 Vermont Avenue N. W. , Washington, D.C., 20420: Veterans Benefits Administration, 2013:82.
Hesser H, Westin V, Hayes SC, Andersson G. Clients' in-session acceptance and cognitive defusion behaviors in acceptance-based treatment of tinnitus distress. Behav Res Ther. 2009 Jun;47(6):523-8. doi: 10.1016/j.brat.2009.02.002. Epub 2009 Feb 10.
PubMed 19268281Crocetti A, Forti S, Ambrosetti U, Bo LD. Questionnaires to evaluate anxiety and depressive levels in tinnitus patients. Otolaryngol Head Neck Surg. 2009 Mar;140(3):403-5. doi: 10.1016/j.otohns.2008.11.036.
PubMed 19248952Hasson D, Theorell T, Wallen MB, Leineweber C, Canlon B. Stress and prevalence of hearing problems in the Swedish working population. BMC Public Health. 2011 Feb 23;11:130. doi: 10.1186/1471-2458-11-130.
PubMed 21345187Hebert S, Fullum S, Carrier J. Polysomnographic and quantitative electroencephalographic correlates of subjective sleep complaints in chronic tinnitus. J Sleep Res. 2011 Mar;20(1 Pt 1):38-44. doi: 10.1111/j.1365-2869.2010.00860.x.
PubMed 20561177Stevens C, Walker G, Boyer M, Gallagher M. Severe tinnitus and its effect on selective and divided attention. Int J Audiol. 2007 May;46(5):208-16. doi: 10.1080/14992020601102329.
PubMed 17487668Rossiter S, Stevens C, Walker G. Tinnitus and its effect on working memory and attention. J Speech Lang Hear Res. 2006 Feb;49(1):150-60. doi: 10.1044/1092-4388(2006/012).
PubMed 16533080Namas R, Ghuma A, Hermus L, Zamora R, Okonkwo DO, Billiar TR, Vodovotz Y. The acute inflammatory response in trauma / hemorrhage and traumatic brain injury: current state and emerging prospects. Libyan J Med. 2009 Sep 1;4(3):97-103. doi: 10.4176/090325.
PubMed 21483522Eyre H, Baune BT. Neuroplastic changes in depression: a role for the immune system. Psychoneuroendocrinology. 2012 Sep;37(9):1397-416. doi: 10.1016/j.psyneuen.2012.03.019. Epub 2012 Apr 21.
PubMed 22525700Beattie EC, Stellwagen D, Morishita W, Bresnahan JC, Ha BK, Von Zastrow M, Beattie MS, Malenka RC. Control of synaptic strength by glial TNFalpha. Science. 2002 Mar 22;295(5563):2282-5. doi: 10.1126/science.1067859.
PubMed 11910117Steinmetz CC, Turrigiano GG. Tumor necrosis factor-alpha signaling maintains the ability of cortical synapses to express synaptic scaling. J Neurosci. 2010 Nov 3;30(44):14685-90. doi: 10.1523/JNEUROSCI.2210-10.2010.
PubMed 21048125Stellwagen D, Malenka RC. Synaptic scaling mediated by glial TNF-alpha. Nature. 2006 Apr 20;440(7087):1054-9. doi: 10.1038/nature04671. Epub 2006 Mar 19.
PubMed 16547515Schaette R, Kempter R. Computational models of neurophysiological correlates of tinnitus. Front Syst Neurosci. 2012 May 8;6:34. doi: 10.3389/fnsys.2012.00034. eCollection 2012.
PubMed 22586377