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, Howard Eliot Gendelman, L. Sharer, D. Eckstein, A. P. Kerza-Kwiateck

Research output: Contribution to journalArticle

58 Citations (Scopus)

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

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Randomized Controlled Trials
HIV
Placebos
Exanthema
Therapeutics
Safety
Central Nervous System Diseases
CD4 Lymphocyte Count
Cognitive Dysfunction
CPI 1189
Viral Load
Double-Blind Method
Cataract
Animal Models
Tumor Necrosis Factor-alpha
Antioxidants
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Clifford, D. B., McArthur, J. C., Schifitto, G., Kieburtz, K., McDermott, M. P., Letendre, S., ... Kerza-Kwiateck, A. P. (2002). A randomized clinical trial of CPI-1189 for HIV-associated cognitive-motor impairment. Neurology, 59(10), 1568-1573. https://doi.org/10.1212/01.WNL.0000034177.47015.DA

A randomized clinical trial of CPI-1189 for HIV-associated cognitive-motor impairment. / Clifford, David B.; McArthur, Justin C.; Schifitto, Giovanni; Kieburtz, Karl; McDermott, M. P.; Letendre, Scott; Cohen, Bruce A.; Marder, Karen; Ellis, Ronald J.; Marra, C. M.; Bornemann, Heather; Brocht, Alicia; Caselli, Cynthia J.; Conn, Kelly; De Blieck, Elisabeth A.; Honsinger, Katherine; Josephson, Lee; Kamp, Cornelia; Orme, Constance; Preston, Larry; Rothenburgh, Karen; McDermott, Michael; Bausch, January; Clouse, Ronda Friedman; Todak, George; Beltre, Jose; Auran, James; Sacktor, Ned; Selnes, Ola; Hill, Coleman; Berzins, Baiba; Cooper, Catherine; Byers, Elaine; Murphy, Robert; Paella, Frank; Hirschtick, Robert; Cruttenden, Kim; Hickey, Charlyne; Palumbo, Donna; McCarthy, Mary; Meshekow, Marilynn; Kraft-Weinberg, Katherine; Monzones, Jennifer; Childers, Meredith; Marra, Christina; Maenza, Janine; Schwartz, Margot; Perrin, Margot E.; Glicksman, Meredith; Kessells, Lisa; Gould, Mary; McGuire, Kristin H.; Philips, Clara; West, Jamie Sue; Garland, W. A.; Flitter, W. D.; Shoulson, I.; Oakes, D.; Reichman, R.; Jubelt, B.; Barton, B.; Gendelman, Howard Eliot; Sharer, L.; Eckstein, D.; Kerza-Kwiateck, A. P.

In: Neurology, Vol. 59, No. 10, 26.11.2002, p. 1568-1573.

Research output: Contribution to journalArticle

Clifford, DB, McArthur, JC, Schifitto, G, Kieburtz, K, McDermott, MP, Letendre, S, Cohen, BA, Marder, K, Ellis, RJ, Marra, CM, Bornemann, H, Brocht, A, Caselli, CJ, Conn, K, De Blieck, EA, Honsinger, K, Josephson, L, Kamp, C, Orme, C, Preston, L, Rothenburgh, K, McDermott, M, Bausch, J, Clouse, RF, Todak, G, Beltre, J, Auran, J, Sacktor, N, Selnes, O, Hill, C, Berzins, B, Cooper, C, Byers, E, Murphy, R, Paella, F, Hirschtick, R, Cruttenden, K, Hickey, C, Palumbo, D, McCarthy, M, Meshekow, M, Kraft-Weinberg, K, Monzones, J, Childers, M, Marra, C, Maenza, J, Schwartz, M, Perrin, ME, Glicksman, M, Kessells, L, Gould, M, McGuire, KH, Philips, C, West, JS, Garland, WA, Flitter, WD, Shoulson, I, Oakes, D, Reichman, R, Jubelt, B, Barton, B, Gendelman, HE, Sharer, L, Eckstein, D & Kerza-Kwiateck, AP 2002, 'A randomized clinical trial of CPI-1189 for HIV-associated cognitive-motor impairment', Neurology, vol. 59, no. 10, pp. 1568-1573. https://doi.org/10.1212/01.WNL.0000034177.47015.DA
Clifford DB, McArthur JC, Schifitto G, Kieburtz K, McDermott MP, Letendre S et al. A randomized clinical trial of CPI-1189 for HIV-associated cognitive-motor impairment. Neurology. 2002 Nov 26;59(10):1568-1573. https://doi.org/10.1212/01.WNL.0000034177.47015.DA
Clifford, David B. ; McArthur, Justin C. ; Schifitto, Giovanni ; Kieburtz, Karl ; McDermott, M. P. ; Letendre, Scott ; Cohen, Bruce A. ; Marder, Karen ; Ellis, Ronald J. ; Marra, C. M. ; Bornemann, Heather ; Brocht, Alicia ; Caselli, Cynthia J. ; Conn, Kelly ; De Blieck, Elisabeth A. ; Honsinger, Katherine ; Josephson, Lee ; Kamp, Cornelia ; Orme, Constance ; Preston, Larry ; Rothenburgh, Karen ; McDermott, Michael ; Bausch, January ; Clouse, Ronda Friedman ; Todak, George ; Beltre, Jose ; Auran, James ; Sacktor, Ned ; Selnes, Ola ; Hill, Coleman ; Berzins, Baiba ; Cooper, Catherine ; Byers, Elaine ; Murphy, Robert ; Paella, Frank ; Hirschtick, Robert ; Cruttenden, Kim ; Hickey, Charlyne ; Palumbo, Donna ; McCarthy, Mary ; Meshekow, Marilynn ; Kraft-Weinberg, Katherine ; Monzones, Jennifer ; Childers, Meredith ; Marra, Christina ; Maenza, Janine ; Schwartz, Margot ; Perrin, Margot E. ; Glicksman, Meredith ; Kessells, Lisa ; Gould, Mary ; McGuire, Kristin H. ; Philips, Clara ; West, Jamie Sue ; Garland, W. A. ; Flitter, W. D. ; Shoulson, I. ; Oakes, D. ; Reichman, R. ; Jubelt, B. ; Barton, B. ; Gendelman, Howard Eliot ; Sharer, L. ; Eckstein, D. ; Kerza-Kwiateck, A. P. / A randomized clinical trial of CPI-1189 for HIV-associated cognitive-motor impairment. In: Neurology. 2002 ; Vol. 59, No. 10. pp. 1568-1573.
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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.",
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TY - JOUR

T1 - A randomized clinical trial of CPI-1189 for HIV-associated cognitive-motor impairment

AU - Clifford, David B.

AU - McArthur, Justin C.

AU - Schifitto, Giovanni

AU - Kieburtz, Karl

AU - McDermott, M. P.

AU - Letendre, Scott

AU - Cohen, Bruce A.

AU - Marder, Karen

AU - Ellis, Ronald J.

AU - Marra, C. M.

AU - Bornemann, Heather

AU - Brocht, Alicia

AU - Caselli, Cynthia J.

AU - Conn, Kelly

AU - De Blieck, Elisabeth A.

AU - Honsinger, Katherine

AU - Josephson, Lee

AU - Kamp, Cornelia

AU - Orme, Constance

AU - Preston, Larry

AU - Rothenburgh, Karen

AU - McDermott, Michael

AU - Bausch, January

AU - Clouse, Ronda Friedman

AU - Todak, George

AU - Beltre, Jose

AU - Auran, James

AU - Sacktor, Ned

AU - Selnes, Ola

AU - Hill, Coleman

AU - Berzins, Baiba

AU - Cooper, Catherine

AU - Byers, Elaine

AU - Murphy, Robert

AU - Paella, Frank

AU - Hirschtick, Robert

AU - Cruttenden, Kim

AU - Hickey, Charlyne

AU - Palumbo, Donna

AU - McCarthy, Mary

AU - Meshekow, Marilynn

AU - Kraft-Weinberg, Katherine

AU - Monzones, Jennifer

AU - Childers, Meredith

AU - Marra, Christina

AU - Maenza, Janine

AU - Schwartz, Margot

AU - Perrin, Margot E.

AU - Glicksman, Meredith

AU - Kessells, Lisa

AU - Gould, Mary

AU - McGuire, Kristin H.

AU - Philips, Clara

AU - West, Jamie Sue

AU - Garland, W. A.

AU - Flitter, W. D.

AU - Shoulson, I.

AU - Oakes, D.

AU - Reichman, R.

AU - Jubelt, B.

AU - Barton, B.

AU - Gendelman, Howard Eliot

AU - Sharer, L.

AU - Eckstein, D.

AU - Kerza-Kwiateck, A. P.

PY - 2002/11/26

Y1 - 2002/11/26

N2 - 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.

AB - 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.

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