TNF-α Treatment of Blast-Induced Tinnitus

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат Etanercept
  To treat blast or noise induced tinnitus
• Другое Saline
  Placebo

Первичные конечные точки

• Tinnitus Functional Index (TFI) [Срок оценки: 12 Weeks]

Вторичные конечные точки (4)

• Audiometric testing [Срок оценки: 12 Weeks]
• Tinnitus Testing [Срок оценки: 12 Weeks]
• Visual Numeric Rating Scale [Срок оценки: 12 Weeks]
• Tinnitus Primary Function Questionnaire [Срок оценки: 12 Weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

• 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.

a) 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 4 центра

• Advent Health — Celebration
• University of Miami — Coral Gables
• Wayne State University — Detroit
• Michigan Ear Institute — Farmington Hills

Публикации

• 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.0b013e3 PMID 22156949
• Lew 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. PMID 18075949
• VBA. 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. PMID 19268281
• Crocetti 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. PMID 19248952
• Hasson 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. PMID 21345187
• Hebert 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. PMID 20561177
• Stevens 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. PMID 17487668

Идентификаторы

NCT: NCT04066348 · PR172190

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗