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


CONCLUSIONS
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.
Schifitto
G
G
Department of Neurology, Movement & Inherited Neurologic Disorders, Clinical Trials Coordination Center, 1351 Mount Hope Avenue, Suite 223, Rochester, NY 14620, USA. giovanni.schifitto@ctcc.rochester.edu
Zhang
J
J
Evans
S R
SR
Sacktor
N
N
Simpson
D
D
Millar
L L
LL
Hung
V L
VL
Miller
E N
EN
Smith
E
E
Ellis
R J
RJ
Valcour
V
V
Singer
E
E
Marra
C M
CM
Kolson
D
D
Weihe
J
J
Remmel
R
R
Katzenstein
D
D
Clifford
D B
DB
D015526:AIDS Dementia Complex / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology / Q000821:virology; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000188:drug therapy / Q000517:prevention & control / Q000821:virology; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D009483:Neuropsychological Tests; D010919:Placebos; D012642:Selegiline / Q000008:administration & dosage* / Q000009:adverse effects; D017211:Treatment Failure
D000975:Antioxidants; D018696:Neuroprotective Agents; D010919:Placebos; D012642:Selegiline