Vitamin E and memantine in Alzheimer's disease: clinical trial methods and
baseline data.
Author(s): Dysken MW(1), Guarino PD(2), Vertrees JE(3), Asthana S(4), Sano M(5), Llorente
M(6), Pallaki M(7), Love S(8), Schellenberg GD(9), McCarten JR(8), Malphurs
J(10), Prieto S(10), Chen P(7), Loreck DJ(11), Carney S(12), Trapp G(13), Bakshi
RS(13), Mintzer JE(14), Heidebrink JL(15), Vidal-Cardona A(16), Arroyo LM(16),
Cruz AR(17), Kowall NW(18), Chopra MP(18), Craft S(19), Thielke S(19), Turvey
CL(20), Woodman C(20), Monnell KA(21), Gordon K(21), Tomaska J(8), Vatassery
G(8).
Affiliation(s): Author information:
(1)VA Minneapolis Health Care System, Minneapolis, MN, USA. Electronic address:
maurice.dysken@va.gov.
(2)Cooperative Studies Program Coordinating Center, VA Connecticut Healthcare
System, West Haven, CT, USA.
(3)VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center,
Albuquerque, NM, USA.
(4)William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
(5)Bronx Veterans Medical Research Center, New York, NY, USA.
(6)VAMC, Washington, DC, USA.
(7)Louis Stokes Cleveland VAMC, Cleveland, OH, USA.
(8)VA Minneapolis Health Care System, Minneapolis, MN, USA.
(9)University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
(10)VA Miami Healthcare System, Miami, FL, USA.
(11)VA Maryland Healthcare System, University of Maryland Medical School, Department
of Psychiatry, Baltimore, MD, USA.
(12)VA Maryland Healthcare System, Baltimore, MD, USA.
(13)VA North Texas Healthcare System, Dallas, TX, USA.
(14)Ralph H. Johnson VAMC, Medical University of South Carolina, Charleston, SC, USA.
(15)VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.
(16)VA Caribbean Healthcare System, San Juan, PR.
(17)Bay Pines VA Healthcare System, Bay Pines, FL, USA.
(18)VA Boston Healthcare System, Boston, MA, USA.
(19)VA Puget Sound Healthcare System, Department of Psychiatry and Behavioral
Sciences, University of Washington, Seattle, WA, USA.
(20)Iowa City VAMC, University of Iowa, Iowa City, IA, USA.
(21)W.G. (Bill) Hefner VAMC, Salisbury, NC, USA.
Publication date & source: 2014, Alzheimers Dement. , 10(1):36-44
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.
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