A multicenter trial of selegiline transdermal system for HIV-associated cognitive impairment

被引：58

作者：

Schifitto, G. ^{[1
]}

Zhang, J. ^{[1
]}

Evans, S. R. ^{[1
]}

Sacktor, N. ^{[1
]}

Simpson, D. ^{[1
]}

Millar, L. L. ^{[1
]}

Hung, V. L. ^{[1
]}

Miller, E. N. ^{[1
]}

Smith, E. ^{[1
]}

Ellis, R. J. ^{[1
]}

Valcour, V. ^{[1
]}

Singer, E. ^{[1
]}

Marra, C. M. ^{[1
]}

Kolson, D. ^{[1
]}

Weihe, J. ^{[1
]}

Remmel, R. ^{[1
]}

Katzenstein, D. ^{[1
]}

Clifford, D. B. ^{[1
]}

机构：

[1] Clin Trials Coordinat Ctr, Dept Neurol Movement & Inherited Neurol Disorders, Rochester, NY 14620 USA

来源：

NEUROLOGY | 2007年 / 69卷 / 13期

关键词：

OXIDATIVE STRESS; PROTEIN TAT; METHAMPHETAMINE; MOTONEURONS; INFECTION; DAMAGE; BRAIN; AIDS;

D O I：

10.1212/01.wnl.0000268487.78753.0f

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: Cognitive impairment continues to be a significant neurologic complication of HIV infection and has been associated with oxidative stress-induced neuronal injury. Selegiline is an MAO-B inhibitor with antioxidant and neurotrophic properties. This rationale has led to the design and implementation of this Selegiline Transdermal System (STS) study with the primary aims of assessing safety and tolerability of STS as well as improvement in cognitive performance. Methods: HIV-1 infected individuals with impaired cognitive functioning were enrolled in this placebo-controlled, three-arm study of STS across 17 sites. Cognitive impairment was determined using a standard battery of neuropsychological tests. Subjects were randomized to receive STS 3 mg/24 hours, STS 6 mg/24 hours, or matching placebo patches daily. The primary efficacy endpoint was defined as the change in neuropsychological composite Z-score (NPZ-6) from baseline to week 24. Measures of safety included frequencies of adverse experiences and abnormal results on laboratory tests. Results: A total of 128 subjects (88% men, 51% white) were enrolled, median age 45 years. Most subjects (62%) had mild to moderate AIDS dementia complex. The 24-week NPZ-6 median (inter-quartile range) changes were 0.22 (-0.28, 0.55) for the selegiline 3 mg/24 hours arm, 0.21 (-0.18, 0.62) for the selegiline 6 mg/24 hours arm, and 0.28 (-0.16, 0.64) for the placebo arm (a positive score indicates improvement from baseline) (p = 0.914). Severe laboratory abnormalities were few and occurred in similar proportion among the three treatment arms. Conclusion: Selegiline was safe and well tolerated by HIV-infected individuals with cognitive impairment and mild to moderate immune suppression; however, no cognitive or functional improvement was observed in this phase II study.

引用

页码：1314 / 1321

页数：8

共 49 条

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