title: Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Neurology, Emory University School of Medicine, Grady Memorial Hospital, Atlanta, Georgia 30303, USA. tharri4@emory.edu
authors.forename: Taylor
authors.initials: T
authors.lastname: Harrison
authors.forename: Sachiko
authors.initials: S
authors.lastname: Miyahara
authors.forename: Anthony
authors.initials: A
authors.lastname: Lee
authors.forename: Scott
authors.initials: S
authors.lastname: Evans
authors.forename: Barbara
authors.initials: B
authors.lastname: Bastow
authors.forename: David
authors.initials: D
authors.lastname: Simpson
authors.forename: Ian
authors.initials: I
authors.lastname: Gilron
authors.forename: Robert
authors.initials: R
authors.lastname: Dworkin
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: Linda
authors.initials: L
authors.lastname: Wieclaw
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
mesh_terms: D000328:Adult; D000368:Aged; D000700:Analgesics / Q000009:adverse effects / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use*; D015897:Comorbidity; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D000068736:Duloxetine Hydrochloride; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D008691:Methadone / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010147:Pain Measurement; D018579:Patient Selection; D011115:Polyneuropathies / Q000188:drug therapy* / Q000209:etiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D004338:Drug Combinations; D000068736:Duloxetine Hydrochloride; D008691:Methadone; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes
keywords: Antidepressants; HIV; Neuropathic Pain; Opioids
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