Efficacy and safety of AM-111 in the treatment of acute sensorineural hearing loss: A double-blind, randomized, placebo-controlled phase II study

Otology and Neurotology

Volumn 35, Issue 8, 2014, Pages 1317-1326

  Suckfuell, Markus ^a   Lisowska, Grazyna ^b   Domka, Wojciech ^c   Kabacinska, Anna ^d   Morawski, Krzysztof ^e   Bodlaj, Robert ^f   Klimak, Petr ^g   Kostrica, Rom ^h   Meyer, Thomas ⁱ  

^a Martha und Maria Helfen Krankenhaus Munchen   (Germany)

^b MEDICAL UNIVERSITY OF SILESIA   (Poland)

^c Specialist Hospital   (Poland)

^d POMERANIAN MEDICAL UNIVERSITY   (Poland)

^e MEDICAL UNIVERSITY OF WARSAW   (Poland)

^f Private ENT Practice ^*  (Germany)

^g Department of Pathology Regional Hospital   (Czech Republic)

^h MASARYK UNIVERSITY   (Czech Republic)

ⁱ Auris Medical AG   (Switzerland)

Author keywords

Acute acoustic trauma; Apoptosis; Idiopathic sudden sensorineural hearing loss; Intratympanic treatment; Otoprotection; Spontaneous recovery; Tinnitus.

Indexed keywords

D-JNKI-1; NEUROPROTECTIVE AGENT; PEPTIDE;

ADOLESCENT; ADULT; CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG EFFECTS; EARDRUM; FEMALE; HEARING LOSS, SENSORINEURAL; HEARING LOSS, SUDDEN; HUMAN; MALE; MIDDLE AGED; PHASE 2 CLINICAL TRIAL; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL; TINNITUS; TREATMENT OUTCOME; YOUNG ADULT;

ADOLESCENT; ADULT; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; HEARING LOSS, SENSORINEURAL; HEARING LOSS, SUDDEN; HUMANS; MALE; MIDDLE AGED; NEUROPROTECTIVE AGENTS; PEPTIDES; PROSPECTIVE STUDIES; TINNITUS; TREATMENT OUTCOME; TYMPANIC MEMBRANE; YOUNG ADULT;

EID: 84906085974     PISSN: 15317129     EISSN: 15374505     Source Type: Journal    
DOI: 10.1097/MAO.0000000000000466     Document Type: Article

References (43)

1. Stachler RJ, Chandrasekhar SS, Archer SM, et al. Clinical practice guideline: sudden hearing loss. Otolaryngol Head Neck Surg 2012; 146:S1-35.
2. Wang Y, Hirose K, Liberman MC. Dynamics of noise-induced cellular injury and repair in the mouse cochlea. J Assoc Res Otolaryngol 2002;3:248-68.
3. Henderson D, Hu B, Bielefeld E. Patterns and mechanisms of noiseinduced cochlear pathology. In: Schacht J, Popper AN, Fay RR, eds. Auditory Trauma, Protection, and Repair. New York, NY: Springer, 2008:195-217.
4. Tan WJT, Thorne PR, Vlajkovic SM. Noise-induced cochlear inflammation. World J Otorhinolaryngol 2013;3:89-99.
5. Lefebvre PP, Malgrange B, Lallemend F, et al. Mechanisms of cell death in the injured auditory system: otoprotective strategies. Audiol Neurotol 2002;7:165-70.
6. Puel JL, Ruel J, Gervais d'Aldin C, et al. Excitotoxicity and repair of cochlear synapses after noise-trauma induced hearing loss. Neuroreport 1998;9:2109-14.
7. Lin HW, Furman AC, Kujawa SG, Liberman MC. Primary neural degeneration in the guinea pig cochlea after reversible noise-induced threshold shift. J Assoc Res Otolaryngol 2011;12:605-16.
8. Kujawa SG, Liberman MC. Adding insult to injury: cochlear nerve degeneration after ''temporary'' noise-induced hearing loss. J Neurosci 2009;29:14077-85.
9. Plontke S, Zenner HP. Current aspects of hearing loss from occupational and leisure noise. GMS Curr Top Otorhinolaryngol Head Neck Surg 2004;3:Doc06.
10. Wei BP, Stathopoulos D, O'Leary S. Steroids for idiopathic sudden sensorineural hearing loss. Cochrane Database Syst Rev 2013;7: CD003998.
11. Conlin AE, Parnes LS. Treatment of sudden sensorineural hearing loss: II. A meta analysis. Arch Otolaryngol Head Neck Surg 2007; 133:582-86.
12. Spear SA, Schwartz SR. Intratympanic steroids for sudden sensorineural hearing loss: a systematic review. Otolaryngol Head Neck Surg 2011;145:534-43.
13. Labus J, Breil J, Stützer H, et al. Meta-analysis for the effect of medical therapy vs. placebo on recovery of idiopathic sudden hearing loss. Laryngoscope 2010;120:1863-71.
14. Agarwal L, Pothier DD. Vasodilators and vasoactive substances for idiopathic sudden sensorineural hearing loss. Cochrane Database Syst Rev 2009;4:CD003422.
15. Bennett MH, Kertesz T, Perleth M, et al. Hyperbaric oxygen for idiopathic sudden sensorineural hearing loss and tinnitus. Cochrane Database Syst Rev 2012;10:CD004739.
16. Guideline ''Sudden Deafness'' of the German Society for Otorhinolaryngology, Head and Neck Surgery.
17. Bonny C, Oberson A, Negri S, et al. Cell-permeable peptide inhibitors of JNK: novel blockers of A-cell death. Diabetes 2001; 50:77-82.
18. Manning AM, Davis RJ. Targeting JNK for therapeutic benefit: from JUNK to gold? Nat Rev Drug Discov 2003;2:554-65.
19. Zine A, Van de Water TR. The MAPK/JNK signalling pathway offers potential therapeutic targets for the prevention of acquired deafness. Curr Drug Targets CNS Neurol Disord 2004; 3:325-32.
20. Abi-Hachem RN, Zine A, Van De Water TR. The injured cochlea as a target for inflammatory processes, initiation of cell death pathways and application of related otoprotectives strategies. Recent Pat CNS Drug Discov 2010;5:147-63.
21. Hu BH, Henderson D, Nicotera TM. Involvement of apoptosis in progression of cochlear lesion following exposure to intense noise. Hear Res 2002;166:62-71.
22. Ma C, Billings P, Harris JP, et al. Characterization of an experimentally induced inner ear immune response. Laryngoscope 2000; 110:451-56.
23. Barkdull GC, Hondarrague Y, Meyer T, et al. AM-111 reduces hearing loss in a guinea pig model of acute labyrinthitis. Laryngoscope 2007;117:2174-82.
24. Wang J, Van De Water TR, Bonny C, et al. A peptide inhibitor of c-Jun N-terminal kinase (D-JNKI-1) protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss. J Neurosci 2003;23:8596-607.
25. Wang J, Ruel J, Ladrech S, et al. Inhibition of the JNK-mediated mitochondrial cell death pathway restores auditory function in sound exposed animals. Mol Pharmacol 2007;71:654-66.
26. Coleman JK, Littlesunday C, Jackson R, et al. AM-111 protects against permanent hearing loss from acute acoustic trauma. Hear Res 2007;226:70-8.
27. Grindal TC, Sampson EM, Antonelli PJ. AM-111 prevents hearing loss from semicircular canal injury in otitis media. Laryngoscope 2010;120:178-82.
28. Omotehara Y, Hakuba N, Hato N, et al. Protection against ischemic cochlear damage by intratympanic administration of AM-111. Otol Neurotol 2011;32:1422-7.
29. Eshraghi AA, Gupta C, Van De Water TR, et al. Molecular mechanisms involved in cochlear implantation trauma and the protection of hearing and auditory sensory cells by inhibition of c-Jun-N-terminal kinase signalling. Laryngoscope 2013;123:S1-14.
30. Suckfuell M, Canis M, Strieth S, et al. Intratympanic treatment of acute acoustic trauma with a cell-permeable JNK ligand: a prospective randomized phase I/II study. Acta Otolaryngol 1997;127:938-42.
31. Plontke SK, Bauer M, Meisner C. Comparison of pure-tone audiometry analysis in sudden hearing loss studies: lack of agreement for different outcome measures. Otol Neurotol 2007;28:753-63.
32. Huy PT, Sauvaget E. Idiopathic sudden sensorineural hearing loss is not an otologic emergency. Otol Neurotol 2005;26:896-902.
33. Moher D, Schulz KF, Altman D. The CONSORT statement: revised recommendations for improving the quality of reports of parallelgroup randomized trials. JAMA 2001;285:1987-91.
34. Jerger J, Jerger S. Measurement of hearing in adults. In: Paparella MM, Shumrick DA, eds. Otolaryngology, 2nd ed. Philadelphia, PA: WB Saunders, 1980:1225-49.
35. Cvorović L, Deric D, Probst R, Hegemann S. Prognostic model for predicting hearing recovery in idiopathic sudden sensorineural hearing loss. Otol Neurotol 2008;29:464-9.
36. Rauch SD, Halpin CF, Antonelli PJ, et al. Oral vs intratympanic corticosteroid therapy for idiopathic sudden sensorineural hearing loss: a randomized trial. JAMA 2011;305:2071-9.
37. Nosrati-Zarenoe R, Hultcrantz E. Corticosteroid treatment of idiopathic sudden sensorineural hearing loss: randomized triple-blind placebo-controlled trial. Otol Neurotol 2012;33:523-31.
38. Labatut T, Daza MJ, Alonso A. Intratympanic steroids as primary initial treatment of idiopathic sudden sensorineural hearing loss. Eur Arch Otorhinolaryngol 2013;270:2823-32.
39. Chen C, Halpin C, Rauch S. Oral steroid treatment for sudden sensorineural hearing loss: a ten year retrospective analysis. Otol Neurotol 2003;24:728-33.
40. Halpin C, Rauch SD. Using audiometric thresholds and word recognition in a treatment study. Otol Neurotol 2006;27:110-6.
41. Bogoyevitch MA, Ngoei KRW, Zhao TT. c-Jun N-terminal kinase (JNK) signaling: recent advances and challenges. Biochim Biophys Acta 2010;1804:463-75.
42. Cardozo AK, Buchillier V, Mathieu M, et al. Cell-permeable peptides induce dose- and length-dependent cytotoxic effects. Biochim Biophys Acta 2007;1768:2222-34.
43. Schramm HM. The role of the osteoimmune axis in the inflammation of the inner auditory ear and with regard to the putative anticarcinogenetic principle: part 2. Inflamm Allergy Drug Targets 2010;9:120-9.