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From University of Rochester (G.S.), NY; Harvard School of Public Health (J.Z., S.R.E.), Boston, MA; Johns Hopkins University School of Medicine (N.S.), Baltimore, MD; Mount Sinai School of Medicine (D.S.), New York, NY; Frontier Science and Technology Research Foundation (L.L.M.), Amherst, NY; ACTG Operations Center (V.L.H.), Silver Spring, MD; UCLA Semel Institute for Neuroscience (E.N.M.), Los Angeles, CA; PMB (E. Smith), TRP, DAIDS, NIAID, NIH, Bethesda, MD; University of California at San Diego (R.J.E.); University of Hawaii (V.V.), Honolulu; University of California at Los Angeles (E. Singer); University of Washington (C.M.M.), Seattle; University of Pennsylvania (D. Kolson), Philadelphia; HIV Community Representative (J.W.); University of Minnesota (R.R.), Minneapolis; Stanford University Medical Center (D. Katzenstein), CA; and Washington University School of Medicine (D.B.C.), St. Louis, MO.
Address correspondence and reprint requests to Dr. Giovanni Schifitto, Department of Neurology, Movement & Inherited Neurologic Disorders, Clinical Trials Coordination Center, 1351 Mount Hope Avenue, Suite 223, Rochester, NY 14620 giovanni.schifitto{at}ctcc.rochester.edu
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.
Editorial, see page 1308
Supplemental data at www.neurology.org
e-Pub ahead of print on July 25, 2007, at www.neurology.org.
*See the appendix for a list of Team members.
Supported in part by the Adult AIDS Clinical Trials Group funded by NIAID, AI38858, AI38855, AI27670, AI27668, AI27658, AI34853, AI27660, AI27664, A127659, AI25903, AI25915, AI046376-05, AI46370, AI46381, AI50410, AI25868, AI46386, the Neurologic AIDS Research Consortium funded by the National Institute of Neurologic Diseases and Stroke, NS32228, the National Institute of Mental Health, MH64409, and GCRC Units funded by the NCRR, RR00052, RR00044, RR00046. Normative data for cognitive function were collected by the Multicenter AIDS Cohort Study (MACS) with centers (Principal Investigators) at The Johns Hopkins University Bloomberg School of Public Health (Joseph B. Margolick, Alvaro Muñoz), Howard Brown Health Center and Northwestern University Medical School (John Phair), University of California, Los Angeles (Roger Detels, Beth Jamieson), and University of Pittsburgh (Charles Rinaldo, PhD). The MACS is funded by the National Institute of Allergy and Infectious Diseases, with additional supplemental funding from the National Cancer Institute. UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041.
Disclosure: Dr. Miller is the author and distributor of the CalCAP reaction time program and has a financial interest in this software.
Received September 18, 2006. Accepted in final form April 16, 2007.
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