Vitamin E and memantine in Alzheimer's disease: Clinical trial methods and baseline data

被引:34
作者
Dysken, Maurice W. [1 ]
Guarino, Peter D. [2 ]
Vertrees, Julia E. [3 ]
Asthana, Sanjay [4 ]
Sano, Mary [5 ]
Llorente, Maria [6 ]
Pallaki, Muralidhar [7 ]
Love, Susan [1 ]
Schellenberg, Gerard D. [8 ]
McCarten, J. Riley [1 ]
Malphurs, Julie [9 ]
Prieto, Susana [9 ]
Cheng, Peijun [7 ]
Loreck, David J. [10 ]
Carneyk, Sara [11 ]
Trapp, George [12 ]
Bakshi, Rajbir S. [12 ]
Mintzer, Jacobo E. [13 ]
Heidebrink, Judith L. [14 ]
Vidal-Cardona, Ana [15 ]
Arroyo, Lillian M. [15 ]
Cruz, Angel R. [16 ]
Kowall, Neil W. [17 ]
Chopra, Mohit P. [17 ]
Craft, Suzanne [18 ]
Thielke, Stephen [18 ]
Turvey, Carolyn L. [19 ]
Woodman, Catherine [19 ]
Monnell, Kimberly A. [20 ]
Gordon, Kimberly [20 ]
Tomaska, Julie [1 ]
Vatassery, Govind [1 ]
机构
[1] VA Minneapolis Hlth Care Syst, Minneapolis, MN 55417 USA
[2] VA Connecticut Healthcare Syst, Cooperat Studies Program Coordinating Ctr, West Haven, CT USA
[3] Clin Res Pharm Coordinating Ctr, VA Cooperat Studies Program, Albuquerque, NM USA
[4] William S Middleton Mem Vet Adm Med Ctr, New York, NY USA
[5] Bronx Vet Med Res Ctr, New York, NY USA
[6] VAMC, Washington, DC USA
[7] Louis Stokes Cleveland VAMC, Cleveland, OH USA
[8] Univ Penn, Sch Med, Philadelphia, PA 19104 USA
[9] VA Miami Healthcare Syst, Miami, FL USA
[10] Univ Maryland, Sch Med, Dept Psychiat, VA Maorland Healthcare Syst, Baltimore, MD 21201 USA
[11] VA Maryland Healthcare Syst, Baltimore, MD USA
[12] VA NorthTexas Healthcare Syst, Dallas, TX USA
[13] Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA
[14] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA
[15] VA Caribbean Healthcare Syst, San Juan, PR USA
[16] Bay Pines VA Healthcare Syst, Bay Pines, FL USA
[17] VA Boston Healthcare Syst, Boston, MA USA
[18] Univ Washington, Dept Psychiat & Behav Sci, VA Puget Sound Healthcare Syst, Seattle, WA 98195 USA
[19] Univ Iowa, Iowa City VAMC, Iowa City, IA USA
[20] WG Bill Hefner VAMC, Salisbury, NC USA
关键词
Alzheimer's disease; Alpha-tocopherol; Vitamin E; Memantine; Cholinesterase inhibitors; Randomized trials; DOUBLE-BLIND; COGNITIVE DECLINE; PROSTATE-CANCER; CO-MORBIDITY; MODERATE; PLACEBO; SUPPLEMENTATION; PREVENTION; INVENTORY; SELENIUM;
D O I
10.1016/j.jalz.2013.01.014
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: Alzheimer's disease (AD) has been associated with both oxidative stress and excessive glutamate activity. A clinical trial was designed to compare the effectiveness of (i) alpha-tocopherol, a vitamin E antioxidant; (ii) memantine (Namenda), an N-methyl-D-aspartate antagonist; (iii) their combination; and (iv) placebo in delaying clinical progression in AD. Methods: The Veterans Affairs Cooperative Studies Program initiated a multicenter, randomized, double-blind, placebo-controlled trial in August 2007, with enrollment through March 2012 and follow-up continuing through September 2012. Participants with mild-to-moderate AD who were taking an acetylcholinesterase inhibitor were assigned randomly to 2000 IU/day of alpha-tocopherol, 20 mg/day memantine, 2000 IU/day alpha-tocopherol plus 20 mg/day memantine, or placebo. The primary outcome for the study is the Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory. Secondary outcome measures include the Mini-Mental State Examination; the Alzheimer's Disease Assessment Scale, cognitive portion; the Dependence Scale; the Neuropsychiatric Inventory; and the Caregiver Activity Survey. Patient follow-up ranged from 6 months to 4 years. Results: A total of 613 participants were randomized. The majority of the patients were male (97%) and white (86%), with a mean age of 79 years. The mean Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory score at entry was 57 and the mean Mini-Mental State Examination score at entry was 21. Conclusion: This large multicenter trial will address the unanswered question of the long-term safety and effectiveness of alpha-tocopherol, memantine, and their combination in patients with mild-to-moderate AD taking an acetylcholinesterase inhibitor. The results are expected in early 2013. (C) 2014 The Alzheimer's Association. All rights reserved.
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页码:36 / 44
页数:9
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