A randomized, double-blind, placebo-controlled study of histone deacetylase type 6 inhibition for the treatment of painful diabetic peripheral neuropathy
David Michelson,
William W. Chin,
Robert H. Dworkin,
Roy Freeman,
David N. Herrmann,
Ralph Mazitschek,
Rodica Pop-Busui,
Aziz Shaibani,
James Vornov,
Melissa Jones,
Matthew Jarpe,
Brittany Hader,
Theresa Viera,
Michelle Hylan,
Tim Kachmar,
Simon Jones
Affiliations
David Michelson
a Regenacy Pharmaceuticals, Inc, Waltham, MA, USA
William W. Chin
a Regenacy Pharmaceuticals, Inc, Waltham, MA, USA
Robert H. Dworkin
b University of Rochester, Rochester, NY, USA
Roy Freeman
c Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
David N. Herrmann
b University of Rochester, Rochester, NY, USA
Ralph Mazitschek
d Massachusetts General Hospital, Harvard University, Boston, MA, USA
Rodica Pop-Busui
e Department of Internal Medicine, Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, USA
Aziz Shaibani
f Baylor College of Medicine, Houston, TX, USA
James Vornov
g Medpace, Inc. and Johns Hopkins School of Medicine, Baltimore, MD, USA
Abstract. Introduction:. Current treatments for painful diabetic peripheral neuropathy (DPN) are insufficiently effective for many individuals and do not treat nonpain signs and symptoms. The enzyme histone deacetylase type 6 (HDAC6) may play a role in the pathophysiology of painful DPN, and inhibition of HDAC6 has been proposed as a potential treatment. Objectives:. To assess the efficacy and safety of the novel HDAC6 inhibitor ricolinostat for the treatment of painful diabetic peripheral neuropathy. Methods:. We conducted a 12-week randomized, double-blind, placebo-controlled phase 2 study of the efficacy of ricolinostat, a novel selective HDAC6 inhibitor, in 282 individuals with painful DPN. The primary outcome was the change in the patient-reported pain using a daily diary, and a key secondary outcome was severity of nonpain neuropathic signs using the Utah Early Neuropathy Scale (UENS) score. Results:. At the 12-week assessment, changes in average daily pain and UENS scores were not different between the ricolinostat and placebo groups. Conclusion:. These results do not support the use of the HDAC6 inhibitor ricolinostat as a treatment for neuropathic pain in DPN for periods up to 12 weeks.
