A randomized clinical trial of CPI-1189 for HIV-associated cognitive-motor impairment

David B. Clifford, Justin C. McArthur, Giovanni Schifitto, Karl Kieburtz, M. P. McDermott, Scott Letendre, Bruce A. Cohen, Karen Marder, Ronald J. Ellis, C. M. Marra, Heather Bornemann, Alicia Brocht, Cynthia J. Caselli, Kelly Conn, Elisabeth A. De Blieck, Katherine Honsinger, Lee Josephson, Cornelia Kamp, Constance Orme, Larry PrestonKaren Rothenburgh, Michael McDermott, January Bausch, Ronda Friedman Clouse, George Todak, Jose Beltre, James Auran, Ned Sacktor, Ola Selnes, Coleman Hill, Baiba Berzins, Catherine Cooper, Elaine Byers, Robert Murphy, Frank Paella, Robert Hirschtick, Kim Cruttenden, Charlyne Hickey, Donna Palumbo, Mary McCarthy, Marilynn Meshekow, Katherine Kraft-Weinberg, Jennifer Monzones, Meredith Childers, Christina Marra, Janine Maenza, Margot Schwartz, Margot E. Perrin, Meredith Glicksman, Lisa Kessells, Mary Gould, Kristin H. McGuire, Clara Philips, Jamie Sue West, W. A. Garland, W. D. Flitter, I. Shoulson, D. Oakes, R. Reichman, B. Jubelt, B. Barton, H. Gendelman, L. Sharer, D. Eckstein, A. P. Kerza-Kwiateck

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Background: CPI-1189 is a compound with antioxidant properties that blocks tumor necrosis factor-α (TNFα) effects in animal models. It has neuroprotective properties in model systems for HIV-associated neurotoxicity and thus is a candidate for neuroprotective therapy in humans with HIV-associated CNS disease. Objective: To assess the tolerability and safety of CPI-1189 in treating HIV-associated cognitive-motor impairment. Methods: Sixty-four subjects with mild to moderate HIV-associated cognitive-motor impairment were randomized to receive either placebo or 50 or 100 mg daily of CPI-1189 in addition to optimal HIV therapy. Subjects were followed prospectively in a double-masked study for 10 weeks. The primary assessment was tolerability and safety of the compound. Secondary objectives examined neuropsychological and functional change associated with this treatment. Results: The study compound was well tolerated, with 91% of CPI-1189-treated subjects and 76% of placebo-treated subjects completing the trial. Skin rash was seen equally in placebo and active arms, but the only study withdrawals due to skin rash occurred in CPI-1189-treated subjects (n = 2). One subject developed a cataract on drug (100 mg/day). CD4 lymphocyte counts and plasma HIV viral load remained stable in all groups throughout the trial. No significant treatment effects were observed on the change in composite Z-scores for eight neuropsychologic measures (NPZ-8). The Grooved Pegboard Test (nondominant) showed improved performance with CPI-1189 at 100 mg/day (p = 0.01), but no other neuropsychometric or functional measures demonstrated significant improvement. Conclusions: CPI-1189 was well tolerated in HIV subjects with cognitive-motor disorder. This study was not powered to conclusively determine efficacy and showed no consistent treatment-associated improvement in cognitive or functional measures.

Original languageEnglish
Pages (from-to)1568-1573
Number of pages6
JournalNeurology
Volume59
Issue number10
DOIs
StatePublished - Nov 26 2002

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