Experience and Challenges Presented by a Multicenter Crossover Study of Combination Analgesic Therapy for the Treatment of Painful HIV-Associated Polyneuropathies

• Type of Material: Article
• Authors: Taylor Harrison, Emory University; Sachiko Miyahara, Harvard University; Anthony Lee, Harvard University; Scott Evans, Harvard University; Barbara Bastow, Social & Scientific Systems, Inc; David Simpson, Mt Sinai Medical Center; Ian Gilron, Queens University; Robert Dworkin, University of Rochester; Eric S. Daar, Harbor UCLA Medical Center; Linda Wieclaw, Frontier Science & Technology Research Foundation, Inc.; David B. Clifford, Washington University
• Language: English
• Date: 2013-07-01
• Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option D - CC-BY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 American Academy of Pain Medicine
• Final Published Version (URL): http://dx.doi.org/10.1111/pme.12084
• Title of Journal or Parent Work: Pain Medicine
• ISSN: 1526-2375
• Volume: 14
• Issue: 7
• Start Page: 1039
• End Page: 1047
• Grant/Funding Information: Pharmaceutical support (duloxetine study drug and matching placebo) was provided by Eli Lilly.; The project was also supported by the Neurological AIDS Research Consortium, NS32228; and the National Institute of Neurological Diseases and Stroke (NINDS).; The project described was supported by Award Number U01AI068636 from the National Institute of Allergy and Infectious Diseases; and supported by National Institute of Mental Health (NIMH); National Institute of Dental and Craniofacial Research (NIDCR).; Supported in part by grants funded by the National Center for Research Resources.
• Keywords: Antidepressants; Opioids; TOXIC NEUROPATHY; Life Sciences & Biomedicine; Anesthesiology; Science & Technology; General & Internal Medicine; PERIPHERAL NEUROPATHIC PAIN; PLACEBO-CONTROLLED TRIAL; AMITRIPTYLINE; RANDOMIZED CONTROLLED-TRIAL; ANTIRETROVIRAL THERAPY; HIV; DOUBLE-BLIND; RISK-FACTORS; Neuropathic Pain; Medicine, General & Internal; DISTAL SENSORY POLYNEUROPATHY; MENTAL-HEALTH
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Neuroscience

Abstract

Objective: There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared with placebo. Design: This study was a phase II, randomized, double-blind, placebo-controlled, four-period crossover multicenter study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. Results: A total of 15 patients were enrolled from eight study sites and eight patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared with placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study dropout. Conclusions: Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed.