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

Maurice W. Dysken; Peter D. Guarino; Julia E. Vertrees; Sanjay Asthana; Mary Sano; Maria Llorente; Muralidhar Pallaki; Susan Love; Gerard D. Schellenberg; J. Riley McCarten; Julie Malphurs; Susana Prieto; Peijun Chen; David J. Loreck; Sara Carney; George Trapp; Rajbir S. Bakshi; Jacobo E. Mintzer; Judith L. Heidebrink; Ana Vidal-Cardona; Lillian M. Arroyo; Angel R. Cruz; Neil W. Kowall; Mohit P. Chopra; Suzanne Craft; Stephen Thielke; Carolyn L. Turvey; Catherine Woodman; Kimberly A. Monnell; Kimberly Gordon; Julie Tomaska; Govind Vatassery

doi:10.1016/j.jalz.2013.01.014

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

Maurice W. Dysken, Peter D. Guarino, Julia E. Vertrees, Sanjay Asthana, Mary Sano, Maria Llorente, Muralidhar Pallaki, Susan Love, Gerard D. Schellenberg, J. Riley McCarten, Julie Malphurs, Susana Prieto, Peijun Chen, David J. Loreck, Sara Carney, George Trapp, Rajbir S. Bakshi, Jacobo E. Mintzer, Judith L. Heidebrink, Ana Vidal-CardonaLillian M. Arroyo, Angel R. Cruz, Neil W. Kowall, Mohit P. Chopra, Suzanne Craft, Stephen Thielke, Carolyn L. Turvey, Catherine Woodman, Kimberly A. Monnell, Kimberly Gordon, Julie Tomaska, Govind Vatassery

Neurology

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English (US)
Pages (from-to)	36-44
Number of pages	9
Journal	Alzheimer's and Dementia
Volume	10
Issue number	1
DOIs	https://doi.org/10.1016/j.jalz.2013.01.014
State	Published - Jan 2014

Bibliographical note

Funding Information:
The VA Trial of Vitamin E and Memantine in Alzheimer's Disease (TEAM-AD)(CSP #546) was funded by the Department of Veterans Affairs Cooperative Studies Program . Forest Research Institute, a Division of Forest Laboratories, Inc., donated the memantine and matching placebo tablets. DSM Nutritional Products, Inc. , donated the dl-alpha-tocopheryl acetate oil and funding for the purchase of the soybean oil from Arista Industries, Inc. The Department of Veterans Affairs Cooperative Studies Program, as sponsor of the trial, participated in the design and oversaw the conduct of the study but had no input into data collection, management, analysis, and interpretation of the data or preparation, review, or approval of the manuscript.

Keywords

Alpha-tocopherol
Alzheimer's disease
Cholinesterase inhibitors
Memantine
Randomized trials
Vitamin E

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Dysken, M. W., Guarino, P. D., Vertrees, J. E., Asthana, S., Sano, M., Llorente, M., Pallaki, M., Love, S., Schellenberg, G. D., McCarten, J. R., Malphurs, J., Prieto, S., Chen, P., Loreck, D. J., Carney, S., Trapp, G., Bakshi, R. S., Mintzer, J. E., Heidebrink, J. L., ... Vatassery, G. (2014). Vitamin e and memantine in Alzheimer's disease: Clinical trial methods and baseline data. Alzheimer's and Dementia, 10(1), 36-44. https://doi.org/10.1016/j.jalz.2013.01.014

Dysken, MW, Guarino, PD, Vertrees, JE, Asthana, S, Sano, M, Llorente, M, Pallaki, M, Love, S, Schellenberg, GD, McCarten, JR, Malphurs, J, Prieto, S, Chen, P, Loreck, DJ, Carney, S, Trapp, G, Bakshi, RS, Mintzer, JE, Heidebrink, JL, Vidal-Cardona, A, Arroyo, LM, Cruz, AR, Kowall, NW, Chopra, MP, Craft, S, Thielke, S, Turvey, CL, Woodman, C, Monnell, KA, Gordon, K, Tomaska, J & Vatassery, G 2014, 'Vitamin e and memantine in Alzheimer's disease: Clinical trial methods and baseline data', Alzheimer's and Dementia, vol. 10, no. 1, pp. 36-44. https://doi.org/10.1016/j.jalz.2013.01.014

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title = "Vitamin e and memantine in Alzheimer's disease: Clinical trial methods and baseline data",

abstract = "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.",

keywords = "Alpha-tocopherol, Alzheimer's disease, Cholinesterase inhibitors, Memantine, Randomized trials, Vitamin E",

author = "Dysken, {Maurice W.} and Guarino, {Peter D.} and Vertrees, {Julia E.} and Sanjay Asthana and Mary Sano and Maria Llorente and Muralidhar Pallaki and Susan Love and Schellenberg, {Gerard D.} and McCarten, {J. Riley} and Julie Malphurs and Susana Prieto and Peijun Chen and Loreck, {David J.} and Sara Carney and George Trapp and Bakshi, {Rajbir S.} and Mintzer, {Jacobo E.} and Heidebrink, {Judith L.} and Ana Vidal-Cardona and Arroyo, {Lillian M.} and Cruz, {Angel R.} and Kowall, {Neil W.} and Chopra, {Mohit P.} and Suzanne Craft and Stephen Thielke and Turvey, {Carolyn L.} and Catherine Woodman and Monnell, {Kimberly A.} and Kimberly Gordon and Julie Tomaska and Govind Vatassery",

note = "Funding Information: The VA Trial of Vitamin E and Memantine in Alzheimer's Disease (TEAM-AD)(CSP #546) was funded by the Department of Veterans Affairs Cooperative Studies Program . Forest Research Institute, a Division of Forest Laboratories, Inc., donated the memantine and matching placebo tablets. DSM Nutritional Products, Inc. , donated the dl-alpha-tocopheryl acetate oil and funding for the purchase of the soybean oil from Arista Industries, Inc. The Department of Veterans Affairs Cooperative Studies Program, as sponsor of the trial, participated in the design and oversaw the conduct of the study but had no input into data collection, management, analysis, and interpretation of the data or preparation, review, or approval of the manuscript. ",

year = "2014",

month = jan,

doi = "10.1016/j.jalz.2013.01.014",

language = "English (US)",

volume = "10",

pages = "36--44",

journal = "Alzheimer's and Dementia",

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TY - JOUR

T1 - Vitamin e and memantine in Alzheimer's disease

T2 - Clinical trial methods and baseline data

AU - Dysken, Maurice W.

AU - Guarino, Peter D.

AU - Vertrees, Julia E.

AU - Asthana, Sanjay

AU - Sano, Mary

AU - Llorente, Maria

AU - Pallaki, Muralidhar

AU - Love, Susan

AU - Schellenberg, Gerard D.

AU - McCarten, J. Riley

AU - Malphurs, Julie

AU - Prieto, Susana

AU - Chen, Peijun

AU - Loreck, David J.

AU - Carney, Sara

AU - Trapp, George

AU - Bakshi, Rajbir S.

AU - Mintzer, Jacobo E.

AU - Heidebrink, Judith L.

AU - Vidal-Cardona, Ana

AU - Arroyo, Lillian M.

AU - Cruz, Angel R.

AU - Kowall, Neil W.

AU - Chopra, Mohit P.

AU - Craft, Suzanne

AU - Thielke, Stephen

AU - Turvey, Carolyn L.

AU - Woodman, Catherine

AU - Monnell, Kimberly A.

AU - Gordon, Kimberly

AU - Tomaska, Julie

AU - Vatassery, Govind

N1 - Funding Information: The VA Trial of Vitamin E and Memantine in Alzheimer's Disease (TEAM-AD)(CSP #546) was funded by the Department of Veterans Affairs Cooperative Studies Program . Forest Research Institute, a Division of Forest Laboratories, Inc., donated the memantine and matching placebo tablets. DSM Nutritional Products, Inc. , donated the dl-alpha-tocopheryl acetate oil and funding for the purchase of the soybean oil from Arista Industries, Inc. The Department of Veterans Affairs Cooperative Studies Program, as sponsor of the trial, participated in the design and oversaw the conduct of the study but had no input into data collection, management, analysis, and interpretation of the data or preparation, review, or approval of the manuscript.

PY - 2014/1

Y1 - 2014/1

N2 - 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.

AB - 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.

KW - Alpha-tocopherol

KW - Alzheimer's disease

KW - Cholinesterase inhibitors

KW - Memantine

KW - Randomized trials

KW - Vitamin E

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

Abstract

Bibliographical note

Keywords

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