A randomized clinical trial of CPI-1189 for HIV-associated cognitive-motor impairment
A randomized clinical trial of CPI-1189 for HIV-associated cognitive-motor impairment
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DOI：
10.1212/01.wnl.0000034177.47015.da
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发表时间：
2002-11-26
期刊：
影响因子：
9.9
通讯作者：
Marra, CM
中科院分区：
文献类型：
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作者：
Clifford, DB;McArthur, JC;Marra, CM
背景：CPI-1189是一种具有抗氧化特性的化合物，可在动物模型中阻断肿瘤坏死因子-α(TNFpha)的作用。在HIV相关神经毒性的模型系统中，它具有神经保护特性，因此是HIV相关中枢神经系统疾病人类神经保护治疗的候选药物。目的：评价CPI-1189治疗HIV相关性认知运动障碍的耐受性和安全性。方法：64名与HIV相关的轻度到中度认知运动障碍的受试者被随机分为安慰剂或每天50或100毫克的CPI-1189，除最佳的HIV治疗外。受试者被前瞻性地进行了为期10周的双掩蔽研究。初步评估是该化合物的耐受性和安全性。次要目标检查了与这种治疗相关的神经心理和功能变化。结果：研究化合物的耐受性良好，接受CPI-1189治疗的受试者中有91%完成试验，而接受安慰剂治疗的受试者中有76%完成试验。皮疹在安慰剂组和活动组中同样可见，但仅在CPI-1189治疗的受试者中因皮疹而停用的研究(n=2)。一名受试者因服用药物(100毫克/天)而患上白内障。在整个试验过程中，所有组的CD4淋巴细胞计数和血浆HIV病毒载量保持稳定。8项神经心理量表(NPZ-8)的综合Z评分变化均未见明显疗效。凹槽钉板测试(非优势)显示，CPI-1189在每天100毫克时的表现有所改善(p=0.01)，但其他神经心理或功能指标没有显著改善。结论：有认知运动障碍的HIV患者对CPI-1189耐受性良好。这项研究并不能最终确定疗效，也没有显示与治疗相关的认知或功能指标的持续改善。
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.