TY - JOUR
T1 - Selegiline and oxidative stress in HIV-associated cognitive impairment
AU - Schifitto, G.
AU - Yiannoutsos, C. T.
AU - Ernst, T.
AU - Navia, B. A.
AU - Nath, A.
AU - Sacktor, N.
AU - Anderson, C.
AU - Marra, C. M.
AU - Clifford, D. B.
N1 - Funding Information:
A5114, NCT00027040 was supported in part by the AIDS Clinical Trials Group funded by the National Institute of Allergy and Infectious Diseases grants AI38858, AI68636, AI68634, AI069465, AI-069511-02, AI 069434, AI 69432, and AI27660 ; the Neurologic AIDS Research Consortium funded by the National Institute of Neurologic Diseases and Stroke , NS32228 ; the General Clinical Research Center Units funded by the National Center for Research Resources grants RR025005, 5-MO1 RR00044, and UO1-AI 032783-14; CFAR grants 5-P30-AI-045008-09, P30 MH075673, and 2-P01 MH064570-05 ; and the National Institute of Mental Health , MH64409 .
Funding Information:
Dr. Schifitto receives research support from the NIH [MH64409 (PI)]. Dr. Yiannoutsos has received honoraria from the National Cancer Institute, the Susan G. Komen Breast Cancer Foundation, and the Annals of Surgery ; and received research support from the NIH [NIAID 5U01AI069911 (PI), NCI 5U01AI069911 supplement (PI), NICHD 5U01AI069911 supplement (PI), NIMH 5 U01 MH083545-02 (PI), and NINDS 5R01NS036524 (Coinvestigator)]. Dr. Ernst receives research support from NRI Inc., the NIH [NIDA 5K02DA016991-03 (PI), NIMH 2R01MH061427-04-A1 (Coinvestigator), NINDS 2R01NS036524 (Coinvestigator), NIDA 1R01DA021016-03 (Coinvestigator), NCRR 1P20RR011091-14 (Coinvestigator), NCRR G12RR003061-23 (Coinvestigator), NINDS 1U54NS056883-01 (Coinvestigator), NIDA 1R01DA021146 (PI)], and Queen's Medical Center. Dr. Navia receives research support from the NIH [NINDS NS36524 (PI)]. Dr. Nath serves as Associate Editor of the Journal of Neurovirology ; may accrue revenue from the following pending patents: Tat as an Immunogen [Filed: 4/2002]; Diosgenin for Treatment of Neurodegenerative Diseases [JHU Ref 4382 (Filed: 2004)], Role of Kv Channels in Neuroregeneration and Protection [JHU Ref 4986 (Filed: 2006)], Role of Lominoid Compounds as Neuroprotective Agents [JHU Ref 5038 (Filed: 2006)], and Tat ELISA [JHU Ref 5087 (Filed: 2006)]; served as a consultant to and received stock options from Nerveda Inc.; and receives research support from the NIH [NINDS R01NS039253 (PI), NINDS R01AI058842-01A2 (PI), P30 MH075673-01 (PI), R01NS056884 (PI), R25MH080661 (PI), NIDA R01DA024593 (PI), and NINDS R01NS055628 (PI)]. Dr. Sacktor receives research support from the NIH [NIAID AI-35042 (Coinvestigator), NIMH N01MH22005 (Coinvestigator), NIMH MH71150 (PI), NINDS U01-NS32228 (PI), NIMH P30-MH075673 (Core PI), NIMH MH058076 (Coinvestigator), and NIMH MH083465 (PI)]. Ms. Anderson reports no disclosures. Dr. Marra receives royalties from publishing an article in UpToDate (current to date) and from the textbook Infections of the Central Nervous System , 3rd ed. (Lippincott Williams & Wilkins, 2004); and receives research support from the NIH [1R01 NS/AI 34235 (PI), N01 MH22005 (Coinvestigator), and U01 NS 32228 (Site PI)]. Dr. Clifford has served on scientific advisory boards or as a consultant for Biogen Idec, Elan Corporation, Roche, Forest Laboratories, Inc., Genentech, Inc., GlaxoSmithKline ($2500) Millennium Pharmaceuticals, Inc., Schering-Plough Corp., regarding HIV 2007 ($300) Bristol-Myers Squibb, and Genzyme Corporation; received a speaker honorarium from GlaxoSmithKline; receives research support from Pfizer Inc., Schering-Plough Corp., Bavarian Nordic, NeurogesX, GlaxoSmithKline, Tibotec Therapeutics, Boehringer Ingelheim, Gilead Sciences, Inc., and Biogen Idec; and receives research support from the NIH [UO1 NS32228 (PI), UO1 AI69495 (PI), NIMH 22005 CHARTER Project (Site PI), NIDA RO3 DA022137(Coinvestigator), NIMH MH058076 (Site PI), and R21 3857-53187 (PI)].
PY - 2009/12
Y1 - 2009/12
N2 - OBJECTIVE:: To assess the effectiveness of the selegiline transdermal system (STS) in reversing HIV-induced metabolic brain injury (as measured by proton magnetic resonance spectroscopy [MRS]) and in decreasing oxidative stress, measured by CSF protein carbonyl concentration. METHODS:: Sixty-two subjects with HIV-associated cognitive impairment were coenrolled in a 24-week placebo-controlled study (AIDS Clinical Trial Group protocol A5090) and were randomly assigned to receive STS 3 mg/24 h, STS 6 mg/24 h, or matching placebo. Cognitive performance was evaluated using the neuropsychological z score (NPZ)-8 and NPZ-6, as well as cognitive domain scores. Subjects underwent proton MRS at study entry and weeks 12 and 24. CSF protein carbonyl was measured at baseline and week 24. RESULTS:: A slight increase in N-acetyl aspartate/creatine from baseline to week 24 was found in the basal ganglia (p = 0.023) and centrum semiovale (p = 0.072) of the placebo group compared with the STS groups; however, there were no significant changes when the absolute metabolite concentrations were analyzed. The levels of choline/creatine in the midfrontal cortex were also significantly higher during the week 12 visit in the combined STS groups. This persisted to the week 24 visit (p = 0.002). Evaluation of the change in NPZ-8, NPZ-6, and cognitive domain scores from baseline to weeks 12 and 24 revealed no significant differences between treatment arms. Protein carbonyl analysis revealed no significant changes among the groups. CONCLUSION:: In this 24-week study, the selegiline transdermal system (STS) had no effect on either magnetic resonance spectroscopy (MRS) metabolites or oxidative stress, as measured by CSF protein carbonyl concentration. The lack of effect on these biomarkers is also reflected in the lack of cognitive improvement in the STS groups compared to placebo. LEVEL OF EVIDENCE:: This study provides Class II evidence that STS had no effect on either MRS metabolites or oxidative stress, as measured by CSF protein carbonyl concentration over a period of 24 weeks.
AB - OBJECTIVE:: To assess the effectiveness of the selegiline transdermal system (STS) in reversing HIV-induced metabolic brain injury (as measured by proton magnetic resonance spectroscopy [MRS]) and in decreasing oxidative stress, measured by CSF protein carbonyl concentration. METHODS:: Sixty-two subjects with HIV-associated cognitive impairment were coenrolled in a 24-week placebo-controlled study (AIDS Clinical Trial Group protocol A5090) and were randomly assigned to receive STS 3 mg/24 h, STS 6 mg/24 h, or matching placebo. Cognitive performance was evaluated using the neuropsychological z score (NPZ)-8 and NPZ-6, as well as cognitive domain scores. Subjects underwent proton MRS at study entry and weeks 12 and 24. CSF protein carbonyl was measured at baseline and week 24. RESULTS:: A slight increase in N-acetyl aspartate/creatine from baseline to week 24 was found in the basal ganglia (p = 0.023) and centrum semiovale (p = 0.072) of the placebo group compared with the STS groups; however, there were no significant changes when the absolute metabolite concentrations were analyzed. The levels of choline/creatine in the midfrontal cortex were also significantly higher during the week 12 visit in the combined STS groups. This persisted to the week 24 visit (p = 0.002). Evaluation of the change in NPZ-8, NPZ-6, and cognitive domain scores from baseline to weeks 12 and 24 revealed no significant differences between treatment arms. Protein carbonyl analysis revealed no significant changes among the groups. CONCLUSION:: In this 24-week study, the selegiline transdermal system (STS) had no effect on either magnetic resonance spectroscopy (MRS) metabolites or oxidative stress, as measured by CSF protein carbonyl concentration. The lack of effect on these biomarkers is also reflected in the lack of cognitive improvement in the STS groups compared to placebo. LEVEL OF EVIDENCE:: This study provides Class II evidence that STS had no effect on either MRS metabolites or oxidative stress, as measured by CSF protein carbonyl concentration over a period of 24 weeks.
UR - http://www.scopus.com/inward/record.url?scp=73349099696&partnerID=8YFLogxK
U2 - 10.1212/WNL.0b013e3181c51a48
DO - 10.1212/WNL.0b013e3181c51a48
M3 - Article
C2 - 19890073
AN - SCOPUS:73349099696
VL - 73
SP - 1975
EP - 1981
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 23
ER -