Intratympanic treatment of acute acoustic trauma with a cell-permeable JNK ligand: a prospective randomized phase I/II study

Acta Otolaryngol. 2007 Sep;127(9):938-42. doi: 10.1080/00016480601110212.


Objectives: Intratympanic administration of a cell-permeable JNK ligand has been shown to prevent hearing loss after acute acoustic trauma in animal models.

Conclusions: Functional and morphological analysis of the treated ears revealed that AM-111 had an excellent otoprotective effect, even when administered hours after the noise exposure. Blocking the signal pathway with D-JNKI-1 is therefore a promising way to protect the morphological integrity and physiological function of the inner ear in various conditions involving acute sensorineural hearing loss.

Subjects and methods: For the first application of AM-111 in humans, we organized a clinical phase I/II trial in patients with acute acoustic trauma after exposure to firecrackers in Berlin and Munich on New Year's Eve 2005/2006. We randomly selected 11 patients for intratympanic treatment with AM-111 at a concentration of 0.4 mg/ml or 2 mg/ml within 24 h after noise exposure. Pure tone audiometry and otoacoustic emissions were assessed before treatment and on days 3 and 30 thereafter.

Results: Based on clinical experience and on a calculation using an empirically derived exponential hearing recovery function AM-111 seems to have had a therapeutic effect. A total of 13 adverse events were reported in 5 study participants. None of the adverse events were serious or severe.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Adult
  • Audiometry, Pure-Tone
  • Double-Blind Method
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Hearing Loss, Noise-Induced / prevention & control*
  • Humans
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Male
  • Middle Aged
  • Peptides / therapeutic use*
  • Prospective Studies
  • Recovery of Function / drug effects


  • Enzyme Inhibitors
  • Peptides
  • JNK Mitogen-Activated Protein Kinases
  • D-JNKI-1