Abstract
Objective: We conducted a study of minocycline to assess its safety, tolerability, and efficacy for the treatment of HIV-associated cognitive impairment. Methods: HIV-1-infected individuals with progressive neurocognitive decline were enrolled in a double-blind, placebo-controlled study of minocycline. Participants were randomized to receive minocycline 100mgor matching placebo orally every 12 hours. The primary efficacy measure was change in a neuropsychological test composite z score (NPZ-8) from baseline to week 24. Measures of safety included the frequency of adverse events and changes over time in laboratory tests. After 50% of participants completed the double-blind phase, an interim analysis of futility for the primary outcome measure was performed, and our Data and Safety Monitoring Board recommended early study termination. Results: A total of 107 HIV-1-infected individuals with cognitive impairment were enrolled. The minocycline group did not show improvement in the primary outcome measure (NPZ-8) (mean 24-week change = 0.12) compared to placebo (mean 24-week change = 0.17) (95% confidence interval = [-0.26, 0.39], p = 0.70). There were few severe adverse events or laboratory abnormalities in either treatment group. Conclusion: Minocycline was safe and well-tolerated in individuals with HIV-associated cognitive impairment, but cognitive improvement was not observed. Classification of evidence. This interventional study provides Class II evidence for the safety, tolerability, and efficacy of minocycline for the treatment of HIV-associated cognitive impairment.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1135-1142 |
| Number of pages | 8 |
| Journal | Neurology |
| Volume | 77 |
| Issue number | 12 |
| DOIs | |
| State | Published - Sep 20 2011 |
| Externally published | Yes |
ASJC Scopus subject areas
- Clinical Neurology
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Minocycline treatment for HIV-associated cognitive impairment : Results from a randomized trial. / Sacktor, N.; Miyahara, S.; Deng, L.; Evans, S.; Schifitto, G.; Cohen, B. A.; Paul, R.; Robertson, K.; Jarocki, B.; Scarsi, K.; Coombs, R. W.; Zink, M. C.; Nath, A.; Smith, E.; Ellis, R. J.; Singer, E.; Weihe, J.; McCarthy, S.; Hosey, L.; Clifford, D. B.
In: Neurology, Vol. 77, No. 12, 20.09.2011, p. 1135-1142.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Minocycline treatment for HIV-associated cognitive impairment
T2 - Results from a randomized trial
AU - Sacktor, N.
AU - Miyahara, S.
AU - Deng, L.
AU - Evans, S.
AU - Schifitto, G.
AU - Cohen, B. A.
AU - Paul, R.
AU - Robertson, K.
AU - Jarocki, B.
AU - Scarsi, K.
AU - Coombs, R. W.
AU - Zink, M. C.
AU - Nath, A.
AU - Smith, E.
AU - Ellis, R. J.
AU - Singer, E.
AU - Weihe, J.
AU - McCarthy, S.
AU - Hosey, L.
AU - Clifford, D. B.
N1 - Funding Information: Dr. Sacktor receives support from the NIH (NIMH, NINDS, NIA, NIDA, Fogerty Institute, NIAID). Dr. Miyahara receives support from the NIH (NINDS, NIAID). L. Deng is supported by grants for the Neurologic AIDS Research Consortium (NINDS, NIH), the Statistical and Data Management Center of the Adult AIDS Clinical Trials Group (NIAID, NIH), and the Oral HIV/AIDS Research Alliance (NIDCR, NIH). Dr. Evans serves on data monitoring committees/scientific advisory boards for the FDA, NIH (NIAID and NICHD), Massachusetts General Hospital, Boston University, HIV Neurobehavioral Research Center (University of California at San Diego), Pfizer Inc, Genentech, Inc., Roche, CIS Biotech, Inc., InterMune, FzioMed, Inc., Alcon, Millennium Pharmaceuticals, Inc., and Averion International Corp.; and receives research support from the NIH (NINDS, NIAID, NIAID, NIMH, and NIDCR). Dr. Schifitto served as a consultant for Pfizer, Novartis, and Tibotec Therapeutics; received funding for travel from Biogen Idec; and receives research support from NIH. Dr. Cohen served as a consultant for Acorda Therapeutics Inc., Genzyme Corporation, Novartis, Pfizer Inc, and Astellas Pharma Inc.; served on speakers' bureaus for Bayer Schering Pharma, EMD Serono, Inc., and Teva Pharmaceutical Industries Ltd.; and received research support from Biogen Idec, Bristol-Myers Squibb, EMD Serono, Inc., Novartis, sanofi-aventis, and the NIH (NINDS, NIAID). Dr. Paul receives research support from the NIH. Dr. Robertson serves on scientific advisory boards for and has received funding for travel or speaker honoraria from GlaxoSmithKline, Abbott, and Tibotec Therapeutics; and receives research support from the NIH (NIMH, NIAID, and NINDS). B. Jarocki reports no disclosures. Dr. Scarsi receives research and salary support from the NIH (NIAID and Fogarty International Center) and the Department of Health and Human Services; and receives research support from the Ralph and Marion Falk and the Society of Infectious Diseases Pharmacists. Dr. Coombs received an honorarium for serving as an adjudicator for a Merck-sponsored study; served on a scientific advisory board for Abbott; serves as a consultant for NexBio, Inc.; and receives research support from the NIH (NIAID/DAIDS). Dr. Zink serves on the editorial board of the Journal of Neurovirology ; serves as a consultant for AkaRx, Inc.; and receives research support from the NIH. Dr. Nath serves on scientific advisory boards for Biogen Idec and DioGenix, Inc.; serves as an Associate Editor for the Journal of Neurovirology ; may accrue revenue on patents re: Tat as an immunogen; Diosgenin for treatment of neurodegenerative diseases; Role of Kv channels in neuroregeneration and protection; Role of limonoid compounds as neuroprotective agents; and Tat ELISA; has served as a consultant for N DioGenix, Inc. and Elan Corporation; receives research support from the NIH (NINDS, NIMH); and has provided expert advice in medico-legal cases. Dr. Smith is employed by NIAID, NIH, and DHHS and has no other disclosure. Dr. Ellis has served on the speakers' bureaus for and received speaker honoraria from Abbott and GlaxoSmithKline; served on the editorial board of the Journal of Neuroimmune Pharmacology ; has received research support from the NIH; and his spouse holds stock in Abbott. Dr. Singer has received funding for travel from Biogen Idec and Pfizer Inc; and receives research support from Pfizer Inc and the NIH (NIMH, NCI, NINDS, NIDA). Dr. Weihe, S. McCarthy, and L. Hosey report no disclosures. Dr. Clifford serves/has served on scientific advisory boards for Biogen Idec, Elan Corporation, Roche, Forest Laboratories, Inc., Genentech, Inc., GlaxoSmithKline, Millennium Pharmaceuticals, Inc., Schering-Plough Corp., Bristol-Meyers Squibb, and Genzyme Corporation; received speaker honoraria and funding for travel from GlaxoSmithKline, Millennium Pharmaceuticals, Inc., and Genentech Inc.; has received research support from Pfizer Inc, Schering-Plough Corp., Bavarian Nordic, NeurogesX, GlaxoSmithKline, Tibotec Therapeutics, Boehringer Ingelheim, and Gilead Sciences, Inc.; and receives research support from the NIH (NIMH, NINDS, NIAID, and Fogarty Institutes). Funding Information: Supported in part by the AIDS Clinical Trials Group (ACTG) (full protocol available from the ACTG upon request) funded by: NIAID, AI38858, AI38855, AI27670, AI27668, AI27658, AI34853, AI127660, AI27664, AI27659, AI25903, AI25915, AI046376, AI46370, AI46381, AI50410, AI25868, AI46386, CFAR AI 127757 , the Neurologic AIDS Research Consortium , NS32228 , the National Institute of Mental Health , MH71150, MH64409, AI 068634 , and GCRC Units funded by the National Center for Research Resources (NCRR) , RR00052, RR00044, RR00046 . The NCT number for this study is NCT 00361257 . This study is registered in ClinicalTrials.gov . Participating site ACTG Clinical Trials Unit (CTU) grant numbers include the following: University of California, San Diego Antiviral Research CTU Grant AI069432 , Johns Hopkins University CTU Grant AI069465 , CTSA Grant UL1 RR025005 , UCLA School of Medicine CTU Grant AI069424 , Washington University (St. Louis) CTU Grant AI069495 , The Research & Education Group-Portland CRS CTU Grant AI069503 , Henry Ford Hospital CRS CTU Grant AI069503 , Massachusetts General Hospital CTU Grant AI069472 , NYU/NYC HHC at Bellevue CTU Grant AI069532 , University of Colorado Hospital CTU Grant AI069450 , Northwestern University CTU Grant AI069471 , Virginia Commonwealth University Medical Center CRS CTU Grant AI069503 , University of Washington (Seattle) CTU Grant AI069434 , University of North Carolina CTU Grant AI069423 , University of Rochester Medical Center CTU Grant AI069511 , Emory University, The Ponce de Leon Center CTU Grant AI069452 , University of Pennsylvania, Philadelphia CTU Grant AI069467–04 . Manufacture of the minocycline and matching placebo was funded with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under contract no. N01-AI-05414 . The project described was supported by Award AI068636 from the National Institute of Allergy and Infectious Diseases , National Institute of Mental Health (NIMH), and National Institute of Dental and Craniofacial Research (NIDCR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.
PY - 2011/9/20
Y1 - 2011/9/20
N2 - Objective: We conducted a study of minocycline to assess its safety, tolerability, and efficacy for the treatment of HIV-associated cognitive impairment. Methods: HIV-1-infected individuals with progressive neurocognitive decline were enrolled in a double-blind, placebo-controlled study of minocycline. Participants were randomized to receive minocycline 100mgor matching placebo orally every 12 hours. The primary efficacy measure was change in a neuropsychological test composite z score (NPZ-8) from baseline to week 24. Measures of safety included the frequency of adverse events and changes over time in laboratory tests. After 50% of participants completed the double-blind phase, an interim analysis of futility for the primary outcome measure was performed, and our Data and Safety Monitoring Board recommended early study termination. Results: A total of 107 HIV-1-infected individuals with cognitive impairment were enrolled. The minocycline group did not show improvement in the primary outcome measure (NPZ-8) (mean 24-week change = 0.12) compared to placebo (mean 24-week change = 0.17) (95% confidence interval = [-0.26, 0.39], p = 0.70). There were few severe adverse events or laboratory abnormalities in either treatment group. Conclusion: Minocycline was safe and well-tolerated in individuals with HIV-associated cognitive impairment, but cognitive improvement was not observed. Classification of evidence. This interventional study provides Class II evidence for the safety, tolerability, and efficacy of minocycline for the treatment of HIV-associated cognitive impairment.
AB - Objective: We conducted a study of minocycline to assess its safety, tolerability, and efficacy for the treatment of HIV-associated cognitive impairment. Methods: HIV-1-infected individuals with progressive neurocognitive decline were enrolled in a double-blind, placebo-controlled study of minocycline. Participants were randomized to receive minocycline 100mgor matching placebo orally every 12 hours. The primary efficacy measure was change in a neuropsychological test composite z score (NPZ-8) from baseline to week 24. Measures of safety included the frequency of adverse events and changes over time in laboratory tests. After 50% of participants completed the double-blind phase, an interim analysis of futility for the primary outcome measure was performed, and our Data and Safety Monitoring Board recommended early study termination. Results: A total of 107 HIV-1-infected individuals with cognitive impairment were enrolled. The minocycline group did not show improvement in the primary outcome measure (NPZ-8) (mean 24-week change = 0.12) compared to placebo (mean 24-week change = 0.17) (95% confidence interval = [-0.26, 0.39], p = 0.70). There were few severe adverse events or laboratory abnormalities in either treatment group. Conclusion: Minocycline was safe and well-tolerated in individuals with HIV-associated cognitive impairment, but cognitive improvement was not observed. Classification of evidence. This interventional study provides Class II evidence for the safety, tolerability, and efficacy of minocycline for the treatment of HIV-associated cognitive impairment.
UR - http://www.scopus.com/inward/record.url?scp=80555157650&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80555157650&partnerID=8YFLogxK
U2 - 10.1212/WNL.0b013e31822f0412
DO - 10.1212/WNL.0b013e31822f0412
M3 - Article
C2 - 21900636
AN - SCOPUS:80555157650
VL - 77
SP - 1135
EP - 1142
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 12
ER -