Original Research Article
Experience and Challenges Presented by a Multicenter Crossover Study of Combination Analgesic Therapy for the Treatment of Painful HIV-Associated Polyneuropathies
Conflict of Interest/Disclosure:
Taylor Harrison: Funding support from the National Institute of Neurological Diseases and Stroke (NINDS)/National Institute of Health (NIH).
Sachiko Miyahara: Funding support from NINDS/NIH and National Institute of Allergy and Infectious Disease (NIAID)/NIH.
Anthony Lee: Funding support from NIAID/NIH.
Scott Evans: Funding support from NIAID/NIH.
Barbara Bastow: No funding support for this project.
David Simpson: Funding support from NINDS/NIH.
Ian Gilron: No funding support for this project.
Robert Dworkin: No funding support for this project.
Eric Daar: Funding support from the NIAID and National Institute of Mental Health (NIMH) (NIH).
Linda Wieclaw: Funding support from the NIAID (NIH).
David Clifford: Funding support from NINDS and NIAID (NIH).
Reprint requests to: Taylor Harrison, MD, Department of Neurology, Emory University School of Medicine, Grady Memorial Hospital, 80 Jesse Hill Jr. Drive Box 036, Atlanta, GA 30303, USA. Tel: 404-616-4013; Fax: 404-659-0849; E-mail: firstname.lastname@example.org.
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.
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.
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.
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.