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

被引:21
作者
Harrison, Taylor [1 ]
Miyahara, Sachiko [2 ]
Lee, Anthony [2 ]
Evans, Scott [2 ]
Bastow, Barbara [3 ]
Simpson, David [4 ]
Gilron, Ian [9 ]
Dworkin, Robert [5 ]
Daar, Eric S. [6 ]
Wieclaw, Linda [7 ]
Clifford, David B. [8 ]
机构
[1] Emory Univ, Sch Med, Grady Mem Hosp, Dept Neurol, Atlanta, GA 30303 USA
[2] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA
[3] Social & Sci Syst Inc, Silver Spring, MD USA
[4] Mt Sinai Med Ctr, Dept Neurol, New York, NY 10029 USA
[5] Univ Rochester, Dept Anesthesiol, Rochester, NY USA
[6] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA
[7] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA
[8] Washington Univ, Dept Neurol, St Louis, MO USA
[9] Queens Univ, Kingston, ON, Canada
关键词
HIV; Neuropathic Pain; Antidepressants; Opioids; PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; DISTAL SENSORY POLYNEUROPATHY; PERIPHERAL NEUROPATHIC PAIN; DOUBLE-BLIND; ANTIRETROVIRAL THERAPY; TOXIC NEUROPATHY; MENTAL-HEALTH; RISK-FACTORS; AMITRIPTYLINE;
D O I
10.1111/pme.12084
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
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.
引用
收藏
页码:1039 / 1047
页数:9
相关论文
共 41 条
  • [1] Cannabis in painful HIV-associated sensory neuropathy - A randomized placebo-controlled trial
    Abrams, D. I.
    Jay, C. A.
    Shade, S. B.
    Vizoso, H.
    Reda, H.
    Press, S.
    Kelly, M. E.
    Rowbotham, M. C.
    Petersen, K. L.
    [J]. NEUROLOGY, 2007, 68 (07) : 515 - 521
  • [2] A COMPARATIVE TRIAL OF DIDANOSINE OR ZALCITABINE AFTER TREATMENT WITH ZIDOVUDINE IN PATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION
    ABRAMS, DI
    GOLDMAN, AI
    LAUNER, C
    KORVICK, JA
    NEATON, JD
    CRANE, LR
    GRODESKY, M
    WAKEFIELD, S
    MUTH, K
    KORNEGAY, S
    COHN, DL
    HARRIS, A
    LUSKINHAWK, R
    MARKOWITZ, N
    SAMPSON, JH
    THOMPSON, M
    DEYTON, L
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1994, 330 (10) : 657 - 662
  • [3] 2',3'-DIDEOXYCYTIDINE (DDC) TOXIC NEUROPATHY - A STUDY OF 52 PATIENTS
    BERGER, AR
    AREZZO, JC
    SCHAUMBURG, HH
    SKOWRON, G
    MERIGAN, T
    BOZZETTE, S
    RICHMAN, D
    SOO, W
    [J]. NEUROLOGY, 1993, 43 (02) : 358 - 362
  • [4] Low-dose zalcitabine-related toxic neuropathy: Frequency, natural history, and risk factors
    Blum, AS
    DalPan, GJ
    Feinberg, J
    Raines, C
    Mayjo, K
    Cornblath, DR
    McArthur, JC
    [J]. NEUROLOGY, 1996, 46 (04) : 999 - 1003
  • [5] Use of mental health and substance abuse treatment services among adults with HIV in the United States
    Burnam, MA
    Bing, EG
    Morton, SC
    Sherbourne, C
    Fleishman, JA
    London, AS
    Vitiello, B
    Stein, M
    Bozzette, SA
    Shapiro, MF
    [J]. ARCHIVES OF GENERAL PSYCHIATRY, 2001, 58 (08) : 729 - 736
  • [6] Meta-analysis of the relationship between HIV infection and risk for depressive disorders
    Ciesla, JA
    Roberts, JE
    [J]. AMERICAN JOURNAL OF PSYCHIATRY, 2001, 158 (05) : 725 - 730
  • [7] Mitochondrial alterations with mitochondrial DNA depletion in the nerves of AIDS patients with peripheral neuropathy induced by 2′3′-dideoxycytidine (ddC)
    Dalakas, MC
    Semino-Mora, C
    Leon-Monzon, M
    [J]. LABORATORY INVESTIGATION, 2001, 81 (11) : 1537 - 1544
  • [8] Efficacy and safety of opioid agonists in the treatment of neuropathic pain of nonmalignant origin - Systematic review and meta-analysis of randomized controlled trials
    Eisenberg, E
    McNicol, ED
    Carr, DB
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2005, 293 (24): : 3043 - 3052
  • [9] Clinical validation of the NeuroScreen
    Ellis, RJ
    Evans, SR
    Clifford, DB
    Moo, LR
    McArthur, JC
    Collier, AC
    Benson, C
    Bosch, R
    Simpson, D
    Yiannoutsos, CT
    Yang, YJ
    Robertson, K
    [J]. JOURNAL OF NEUROVIROLOGY, 2005, 11 (06) : 503 - 511
  • [10] Continued High Prevalence and Adverse Clinical Impact of Human Immunodeficiency Virus-Associated Sensory Neuropathy in the Era of Combination Antiretroviral Therapy The CHARTER Study
    Ellis, Ronald J.
    Rosario, Debralee
    Clifford, David B.
    McArthur, Justin C.
    Simpson, David
    Alexander, Terry
    Gelman, Benjamin B.
    Vaida, Florin
    Collier, Ann
    Marra, Christina M.
    Ances, Beau
    Atkinson, J. Hampton
    Dworkin, Robert H.
    Morgello, Susan
    Grant, Igor
    [J]. ARCHIVES OF NEUROLOGY, 2010, 67 (05) : 552 - 558