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

Abstract

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.

• Authors: M Suckfuell, M Canis, S Strieth, H Scherer, A Haisch
• Journal: Acta oto-laryngologica (Acta Otolaryngol) Vol. 127 Issue 9 Pg. 938-42 (Sep 2007) ISSN: 0001-6489 [Print] England
• PMID: 17712672 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)

Chemical References

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

Topics

• 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)