Skip to main content
SpringerLink
Log in

Implementation and Outcomes of Clinical Trials in Immune-Mediated Hearing Loss and Other Rare Diseases

  • Chapter
  • First Online:
Inflammatory Mechanisms in Mediating Hearing Loss

  • 451 Accesses

Abstract

Clinical trials for rare diseases can be challenging to design, meet targeted enrollment, and obtain sufficient evidence of efficacy for FDA labeling of new drugs to treat these orphan diseases. Autoimmune inner ear disease, and related diseases of immune mediated hearing loss are yet to be classified orphan diseases. In this chapter, we have addressed some of the unique challenges in designing clinical trials for Autoimmune Inner Ear Disease, Sudden Sensorineural Hearing Loss, Meniere’s Disease and Autoinflammatory Diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Angeli SI, Abi-Hachem RN, Vivero RJ, Telischi FT, Machado JJ. L-N-Acetylcysteine treatment is associated with improved hearing outcome in sudden idiopathic sensorineural hearing loss. Acta Otolaryngol. 2012;132:369–76.

    Article  CAS  PubMed  Google Scholar 

  • Arriaga MA, Goldman S. Hearing results of intratympanic steroid treatment of endolymphatic hydrops. Laryngoscope. 1998;108:1682–5.

    Article  CAS  PubMed  Google Scholar 

  • Barrs DM, Keyser JS, Stallworth C, McElveen JT Jr. Intratympanic steroid injections for intractable Meniere’s disease. Laryngoscope. 2001;111:2100–4.

    Article  CAS  PubMed  Google Scholar 

  • Broughton SS, Meyerhoff WE, Cohen SB. Immune mediated inner ear disease: 10-year experience. Semin Arthritis Rheum. 2004;34:544–8.

    Article  CAS  PubMed  Google Scholar 

  • Chen CH, Young YH. N-acetylcysteine as a single therapy for sudden deafness. Acta Otolaryngol. 2016;137(1):58–62.

    Article  CAS  PubMed  Google Scholar 

  • Cohen S, Shoup A, Weisman MH, Harris J. Etanercept treatment for autoimmune inner ear disease: results of a pilot placebo-controlled study. Otol Neurotol. 2005;26:903–7.

    Article  PubMed  Google Scholar 

  • Goldbach-Mansky R, et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med. 2006;355:581–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harris JP, Weissman MH, Derebery JM, et al. Treatment of corticosteroid-responsive autoimmune inner ear disease with methotrexate: a randomized controlled trial. JAMA. 2003;290:1875–83.

    Article  CAS  PubMed  Google Scholar 

  • Hietikko E, Sorri M, Mannikko M, Kotimaki J. Higher prevalence of autoimmune diseases and longer spells of vertigo in patients affected with familial Meniere’s disease: a clinical comparison of familial and sporadic Meniere’s disease. Am J Audiol. 2014;23:232–7.

    Article  PubMed  Google Scholar 

  • Hughes GB, Freedman MA, Haberkamp TJ, Guay ME. Sudden sensorineural hearing loss. Otolaryngol Clin N Am. 1996;29:393–405.

    CAS  Google Scholar 

  • Kuemmerle-Deschner JB, et al. Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes. Ann Rheum Dis. 2011;70:2095–102.

    Article  CAS  PubMed  Google Scholar 

  • Kuemmerle-Deschner JB, et al. Hearing loss in Muckle-Wells syndrome. Arthritis Rheum. 2013;65:824–31.

    Article  CAS  PubMed  Google Scholar 

  • Kuemmerle-Deschner JB, Koitschev A, Tyrrell PN, et al. Early detection of sensorineural hearing loss in Muckle-Wells-syndrome. Pediatr Rheumatol Online J. 2015;13:43.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lambert PR, Carey J, Mikulec AA, LeBel C, Otonomy Meniere’s Study, G. Intratympanic sustained-exposure dexamethasone thermosensitive gel for symptoms of Meniere’s disease: randomized phase 2b safety and efficacy trial. Otol Neurotol. 2016;37(10):1669–76.

    Article  PubMed  PubMed Central  Google Scholar 

  • Matteson EL, Choi HK, Poe DS, Wise C, Lowe VJ, McDonald TJ, Rahman MU. Etanercept therapy for immune-mediated cochleovestibular disorders: a multicenter, open-label, pilot study. Arthritis Rheum. 2005;53:337–42.

    Article  CAS  PubMed  Google Scholar 

  • McCabe BF. Autoimmune sensorineural hearing loss. Ann Otol Rhinol Laryngol. 1979;88:585–9.

    Article  CAS  PubMed  Google Scholar 

  • Mirault T, Launay D, Cuisset L, Hachulla E, Lambert M, Queyrel V, Quemeneur T, Morell-Dubois S, Hatron PY. Recopvery from deafness in a patient with Muckle-wells syndrome treated with anakinra. Arthritis Rheum. 2006;54:1697–700.

    Article  PubMed  Google Scholar 

  • Nakagawa T, et al. A randomized controlled clinical trial of topical insulin-like growth factor-1 therapy for sudden deafness refractory to systemic corticosteroid treatment. BMC Med. 2014;12:219.

    Article  PubMed  PubMed Central  Google Scholar 

  • O’Connor JC, et al. Regulation of IGF-I function by proinflammatory cytokines: at the interface of immunology and endocrinology. Cell Immunol. 2008;252:91–110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ombrello MJ, Kastner DL. Autoinflammation in 2010: expanding clinical spectrum and broadening therapeutic horizons. Nat Rev Rheumatol. 2011;7:82–4.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pathak S, Stern C, Vambutas A. N-Acetylcysteine attenuates tumor necrosis factor alpha levels in autoimmune inner ear disease patients. Immunol Res. 2015;63:236–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rauch SD, et al. Oral vs intratympanic corticosteroid therapy for idiopathic sudden sensorineural hearing loss: a randomized trial. JAMA. 2011;305:2071–9.

    Article  CAS  PubMed  Google Scholar 

  • Silverstein H, Isaacson JE, Olds MJ, Rowan PT, Rosenberg S. Dexamethasone inner ear perfusion for the treatment of Meniere’s disease: a prospective, randomized, double-blind, crossover trial. Am J Otol. 1998;19:196–201.

    PubMed  CAS  Google Scholar 

  • Stahle J, Stahle C, Arenberg IK. Incidence of Meniere’s disease. Arch Otolaryngol. 1978;104:99–102.

    Article  CAS  PubMed  Google Scholar 

  • Suckfuell M, Lisowska G, Domka W, et al. Efficacy and safety of AM-111 in the treatment of acute sensorineural hearing loss: a double-blind, randomized, placebo-controlled phase II study. Otol Neurotol. 2014;35:1317–26.

    Article  PubMed  Google Scholar 

  • Vambutas A, Pathak S. AAO: Autoimmune and Autoinflammatory (Disease) in Otology: what is new in immune-mediated hearing loss. Laryngoscope Investig Otolaryngol. 2016;1(5):110–5.

    Article  PubMed  PubMed Central  Google Scholar 

  • Vambutas A, et al. Early efficacy trial of anakinra in corticosteroid-resistant autoimmune inner ear disease. J Clin Invest. 2014;124:4115–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wellman-Labadie O, Zhou Y. The US orphan drug act: rare disease research stimulator or commercial opportunity? Health Policy. 2010;95:216–28.

    Article  PubMed  Google Scholar 

  • Wilson WR, Byl FM, Laird N. The efficacy of steroids in the treatment of idiopathic sudden hearing loss. A double-blind clinical study. Arch Otolaryngol. 1980;106:772–6.

    Article  CAS  PubMed  Google Scholar 

  • Yamazaki T, Masumoto J, Agematsu K, Sawai N, Kobayashi S, Shigemura T, Yasui K, Koike K. Anakinra improves sensory deafness in a japanese patient with Muckle-Wells syndrome, possibly inhibiting the cryopyrin inflammasome. Arthritis Rheum. 2008;58:864–8.

    Article  CAS  PubMed  Google Scholar 

  • Yin F, Jiang T, Cadenas E. Metabolic triad in brain aging: mitochondria, insulin/IGF-1 signalling and JNK signalling. Biochem Soc Trans. 2013;41:101–5.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Otolaryngology and Molecular Medicine, Barbara and Donald Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA

    Andrea Vambutas

  2. Biostatistics Unit, Feinstein Institute for Medical Research, Manhasset, NY, USA

    Martin L. Lesser

  3. Department of Molecular Medicine and Population Health, Barbara and Donald Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA

    Martin L. Lesser

Authors
  1. Andrea Vambutas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martin L. Lesser
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrea Vambutas .

Editor information

Editors and Affiliations

  1. Department of Pharmacology, School of Medicine, Southern Illinois University, Springfield, Illinois, USA

    Vickram Ramkumar

  2. Division of Otolaryngology, Department of Surgery, School of Medicine, Southern Illinois University, Springfield, Illinois, USA

    Leonard P. Rybak

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Vambutas, A., Lesser, M.L. (2018). Implementation and Outcomes of Clinical Trials in Immune-Mediated Hearing Loss and Other Rare Diseases. In: Ramkumar, V., Rybak, L. (eds) Inflammatory Mechanisms in Mediating Hearing Loss. Springer, Cham. https://doi.org/10.1007/978-3-319-92507-3_11

Download citation

Publish with us

Policies and ethics

Search

Navigation