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

Neurology. 2002 Nov 26;59(10):1568-73. doi: 10.1212/01.wnl.0000034177.47015.da.

Abstract

Background: CPI-1189 is a compound with antioxidant properties that blocks tumor necrosis factor-alpha (TNFalpha) 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS Dementia Complex / complications
  • AIDS Dementia Complex / drug therapy*
  • AIDS Dementia Complex / psychology*
  • Adult
  • Antioxidants / therapeutic use*
  • Biomarkers
  • Butanes / adverse effects
  • Butanes / therapeutic use*
  • Cognition Disorders / cerebrospinal fluid
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Movement Disorders / cerebrospinal fluid
  • Movement Disorders / etiology*
  • Neurologic Examination
  • Neuropsychological Tests
  • Nitrogen Oxides / adverse effects
  • Nitrogen Oxides / therapeutic use*
  • Patient Compliance
  • Psychometrics
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antioxidants
  • Biomarkers
  • Butanes
  • Nitrogen Oxides
  • Tumor Necrosis Factor-alpha
  • CPI 1189