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

TitleA multicenter trial of selegiline transdermal system for HIV-associated cognitive impairment.
Publication TypeJournal Article
Year of Publication2007
AuthorsSchifitto G, Zhang J, Evans SR, Sacktor N, Simpson D, Millar LL, Hung VL, Miller EN, Smith E, Ellis RJ, Valcour V, Singer E, Marra CM, Kolson D, Weihe J, Remmel R, Katzenstein D, Clifford DB
Corporate AuthorsACTG A5090 Team
JournalNeurology
Volume69
Issue13
Pagination1314-21
Date Published2007 Sep 25
ISSN1526-632X
KeywordsAdult, Aged, AIDS Dementia Complex, Antioxidants, Brain, Cytoprotection, Female, Humans, Male, Middle Aged, Nerve Degeneration, Neuroprotective Agents, Neuropsychological Tests, Placebos, Selegiline, Treatment Failure
Abstract

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 (interquartile 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.

DOI10.1212/01.wnl.0000268487.78753.0f
Alternate JournalNeurology
PubMed ID17652642
Grant List5-MO1-RR-00722 / RR / NCRR NIH HHS / United States
A127659 / / PHS HHS / United States
AI046376-05 / AI / NIAID NIH HHS / United States
AI25868 / AI / NIAID NIH HHS / United States
AI25903 / AI / NIAID NIH HHS / United States
AI25915 / AI / NIAID NIH HHS / United States
AI27658 / AI / NIAID NIH HHS / United States
AI27660 / AI / NIAID NIH HHS / United States
AI27664 / AI / NIAID NIH HHS / United States
AI27668 / AI / NIAID NIH HHS / United States
AI27670 / AI / NIAID NIH HHS / United States
AI34853 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI46370 / AI / NIAID NIH HHS / United States
AI46381 / AI / NIAID NIH HHS / United States
AI46386 / AI / NIAID NIH HHS / United States
AI50410 / AI / NIAID NIH HHS / United States
MH64409 / MH / NIMH NIH HHS / United States
NS32228 / NS / NINDS NIH HHS / United States
RR00044 / RR / NCRR NIH HHS / United States
RR00046 / RR / NCRR NIH HHS / United States
RR00052 / RR / NCRR NIH HHS / United States
UO1-AI-35039 / AI / NIAID NIH HHS / United States
UO1-AI-35040 / AI / NIAID NIH HHS / United States
UO1-AI-35041 / AI / NIAID NIH HHS / United States
UO1-AI-35042 / AI / NIAID NIH HHS / United States
UO1-AI-35043 / AI / NIAID NIH HHS / United States
UO1-AI-37613 / AI / NIAID NIH HHS / United States
UO1-AI-37984 / AI / NIAID NIH HHS / United States