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 Preston; Karen 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

doi:10.1212/01.WNL.0000034177.47015.DA

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

60 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 language	English (US)
Pages (from-to)	1568-1573
Number of pages	6
Journal	Neurology
Volume	59
Issue number	10
DOIs	https://doi.org/10.1212/01.WNL.0000034177.47015.DA
State	Published - Nov 26 2002

ASJC Scopus subject areas

Clinical Neurology

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Clifford, D. B., McArthur, J. C., Schifitto, G., Kieburtz, K., McDermott, M. P., Letendre, S., Cohen, B. A., Marder, K., Ellis, R. J., Marra, C. M., Bornemann, H., Brocht, A., Caselli, C. J., Conn, K., De Blieck, E. A., Honsinger, K., Josephson, L., Kamp, C., Orme, C., ... 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

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, H, 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

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title = "A randomized clinical trial of CPI-1189 for HIV-associated cognitive-motor impairment",

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.",

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

year = "2002",

month = nov,

day = "26",

doi = "10.1212/01.WNL.0000034177.47015.DA",

language = "English (US)",

volume = "59",

pages = "1568--1573",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams and Wilkins",

number = "10",

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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, H.

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

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