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

Alzheimer's & Dementia - Tập 10 - Trang 36-44 - 2014
Maurice W. Dysken1, Peter D. Guarino2, Julia E. Vertrees3, Sanjay Asthana4, Mary Sano5, Maria Llorente6, Muralidhar Pallaki7, Susan Love1, Gerard D. Schellenberg8, J. Riley McCarten1, Julie Malphurs9, Susana Prieto9, Peijun Chen7, David J. Loreck10, Sara Carney11, George Trapp12, Rajbir S. Bakshi12, Jacobo E. Mintzer13, Judith L. Heidebrink14, Ana Vidal-Cardona15
1VA Minneapolis Health Care System, Minneapolis, MN, USA
2Cooperative Studies Program Coordinating Center, VA Connecticut Healthcare System, West Haven, CT, USA
3VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, NM, USA
4William S. Middleton Memorial Veterans Hospital, Madison, WI, USA
5Bronx Veterans Medical Research Center, New York, NY, USA
6VAMC, Washington, DC, USA
7Louis Stokes Cleveland VAMC, Cleveland, OH, USA
8University of Pennsylvania School of Medicine Philadelphia, PA, USA
9VA Miami Healthcare System, Miami, FL, USA
10VA Maryland Healthcare System, University of Maryland Medical School, Department of Psychiatry, Baltimore, MD, USA
11VA Maryland Healthcare System, Baltimore, MD, USA
12VA North Texas Healthcare System, Dallas, TX, USA
13Ralph H. Johnson VAMC, Medical University of South Carolina, Charleston, SC, USA
14VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.
15VA Caribbean Healthcare System, San Juan, PR

Tóm tắt

AbstractBackground

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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