A Randomized, Clinical Trial of Vitamin E and Memantine in Alzheimer's Disease (TEAM-AD)
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ClinicalTrials.gov Identifier: NCT00235716 |
Recruitment Status :
Completed
First Posted : October 10, 2005
Results First Posted : January 29, 2014
Last Update Posted : July 23, 2014
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Condition or disease | Intervention/treatment | Phase |
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Alzheimer's Disease | Drug: dl-alpha-tocopherol Drug: Memantine Drug: Placebo | Phase 3 |

Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 613 participants |
Allocation: | Randomized |
Intervention Model: | Factorial Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | CSP #546 - A Randomized, Clinical Trial of Vitamin E and Memantine in Alzheimer's Disease (TEAM-AD) |
Study Start Date : | August 2007 |
Actual Primary Completion Date : | September 2012 |
Actual Study Completion Date : | October 2012 |

Arm | Intervention/treatment |
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Experimental: Arm 1
2,000 IU per day of dl-alpha-tocopherol plus placebo for memantine
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Drug: dl-alpha-tocopherol
Alpha-tocopherol will be given as an oral dose of 1000 IU twice a day (morning and evening). The form of vitamin E that will be used in this study will be hard gel capsules of dl-alpha-tocopheryl acetate ("synthetic") vitamin E.
Other Name: Vitamin E |
Experimental: Arm 2
20 mg per day of memantine plus placebo for dl-alpha-tocopherol
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Drug: Memantine
A moderate-affinity NMDA antagonist. Memantine will be titrated over four weeks to a maintenance dose of 10 mg twice a day. During week 1 patients will take one 5-mg memantine tablet in the morning. During week 2 patients will take one 5-mg memantine tablet in the morning and one in the evening. During week 3 patients will take two 5-mg memantine tablets in the morning and one 5-mg tablet in the evening. Beginning with week 4, participants will take four 5-mg tablets daily, two in the morning and two in the evening.
Other Name: Namenda (R) |
Experimental: Arm 3
Combination of 2,000 IU per day of dl-alpha-tocopherol and 20 mg per day of memantine
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Drug: dl-alpha-tocopherol
Alpha-tocopherol will be given as an oral dose of 1000 IU twice a day (morning and evening). The form of vitamin E that will be used in this study will be hard gel capsules of dl-alpha-tocopheryl acetate ("synthetic") vitamin E.
Other Name: Vitamin E Drug: Memantine A moderate-affinity NMDA antagonist. Memantine will be titrated over four weeks to a maintenance dose of 10 mg twice a day. During week 1 patients will take one 5-mg memantine tablet in the morning. During week 2 patients will take one 5-mg memantine tablet in the morning and one in the evening. During week 3 patients will take two 5-mg memantine tablets in the morning and one 5-mg tablet in the evening. Beginning with week 4, participants will take four 5-mg tablets daily, two in the morning and two in the evening.
Other Name: Namenda (R) |
Placebo Comparator: Arm 4
Matching placebos for dl-alpha-tocopherol and memantine
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Drug: Placebo
Matching placebos for dl-alpha-tocopherol and memantine. |
- Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS/ADL) Inventory Change From Baseline [ Time Frame: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline ]The primary outcome of the study was the Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS/ADL) Inventory. The ADCS/ADL Inventory is designed to assess functional abilities to perform activities of daily living in Alzheimer patients with a broad range of dementia severity. The total score ranges from 0 to 78 with higher scores indicating greater abilities. Outcome analysis is average least square means change from baseline.
- Mini-Mental State Examination Change From Baseline [ Time Frame: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline ]The Mini-Mental State Examination (MMSE) briefly and objectively assess cognitive status in psychiatric patients with cognitive impairment. The MMSE questions are grouped into seven categories, each representing a different cognitive domain. The MMSE yields a total score that ranges from 0 for a patient who gives no correct response to a score of 30 for a patient who makes no errors. Outcome analysis is average least square means change from baseline.
- Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog) Change From Baseline [ Time Frame: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline ]The Alzheimer's Disease Assessment Scale (ADAS) is a 21-item scale designed to assess the severity of cognitive and non-cognitive behavioral impairments in patients with Alzheimer's disease. The cognitive portion of the scale (ADAS-cog) consists of 11 items to assess memory, language, and praxis functions. The ADAS-cog total score ranges from 0 (no errors) to 70 (severe cognitive impairment). Outcome analysis is average least square means change from baseline.
- Neuropsychiatric Inventory Change From Baseline [ Time Frame: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline ]The Neuropsychiatric Inventory (NPI) assesses psychological and behavioral problems in patients with dementia. For each of twelve domains, there are four scores: frequency, severity, total frequency x severity, and caregiver distress. The frequency x severity total scores from each domain are summed for an overall total score that ranges from 0 to 144. The total caregiver distress scores are also summed for an overall total caregiver distress score that ranges from 0 to 60. The secondary endpoint for the trial will be the overall frequency times severity total score. Outcome analysis is average least square means change from baseline.
- Caregiver Activity Survey Change From Baseline [ Time Frame: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline ]The Caregiver Activity Survey (CAS) was developed to measure the time caregivers spend aiding Alzheimer patients with their day-to-day activities. The CAS consists of six items that ask for an estimate in hours and minutes of the time that the caregiver spent during the previous 24 hours performing these particular activities. The six CAS items are as follows: 1) communication with the person, 2) using transportation, 3) dressing, 4) eating, 5) looking after one's appearance, and 6) supervising the person. The more caregiving hours the worse the patient's functioning level. Outcome analysis is average least square means change from baseline.
- Dependence Scale: Time to Event Analysis (Increase of of One Dependence Level) [ Time Frame: Every 6 months to a maximum of 4 years ]The Dependence Scale assesses the level of assistance needed by patients with Alzheimer's disease for activities of daily living. The scale yields six levels of dependence: no assistance required (Level 0); requires occasional reminders (Level 1); requires frequent reminders and/or help with household chores (Level 2); needs daily supervision (Level 3); needs to be dressed, toileted or fed (Level 4); needs to be transferred, diapered or tube fed (Level 5).
- All-cause Mortality [ Time Frame: up to 4 years ]Survival analysis of death from any cause.

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Ages Eligible for Study: | 40 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Diagnoses of possible or probable Alzheimer's disease (NINCDS-ADRDA)
- Presence of a caregiver (friend or relative) who can assume responsibility for medication compliance, can accompany the patient to all visits, and rate patient's condition
- Written informed consent from both the patient (or surrogate) and caregiver
- An MMSE score between 12 and 26 inclusive
- Administration of a maintenance dosage of donepezil (5-10mg/d), rivastigmine (6-12mg/d) or rivastigmine (Exelon) patch (4.6 mg or 9.5 mg), galantamine or galantamine ER (16-24mg/d) for a minimum of 4 weeks prior to randomization
- Agreement not to take vitamin E supplements and/or memantine outside of the study (daily multivitamin is permitted containing up to 100 IU alpha-tocopherol)
Exclusion Criteria:
- A non-Alzheimer primary dementia (e.g., vascular dementia, Lewy body dementia, fronto-temporal dementia, vitamin B-12 deficiency, hypothyroidism)
- Current major depression, delirium, alcohol or psychoactive substance abuse or dependency, schizophrenia, or delusional disorder as defined by DSM-IV
- Presence of any uncontrolled systemic illness that would interfere with participation in the study or a life expectancy of less than one year
- Pregnant or intention to become pregnant
- Enrollment in another interventional clinical trial
- Current prescription with more than one AChE inhibitor
- Current prescription for warfarin
- Use of vitamin E supplements in the past 2 weeks
- Use of memantine in the past 4 weeks or known intolerance
- Estimated creatinine clearance less than 5ml/min (Cockcroft-Gault formula)
- Use of amantadine in the past 2 weeks

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00235716
United States, Florida | |
VA Medical Center, Bay Pines | |
Bay Pines, Florida, United States, 33708 | |
VA Medical Center, Miami | |
Miami, Florida, United States, 33125 | |
United States, Iowa | |
VA Medical Center, Iowa City | |
Iowa City, Iowa, United States, 52246-2208 | |
United States, Maryland | |
VA Maryland Health Care System, Baltimore | |
Baltimore, Maryland, United States, 21201 | |
United States, Massachusetts | |
VA Medical Center, Jamaica Plain Campus | |
Boston, Massachusetts, United States, 02130 | |
United States, Michigan | |
VA Ann Arbor Healthcare System | |
Ann Arbor, Michigan, United States, 48113 | |
United States, Minnesota | |
VA Medical Center, Minneapolis | |
Minneapolis, Minnesota, United States, 55417 | |
United States, North Carolina | |
Salisbury VAMC | |
Salisbury, North Carolina, United States, 28144 | |
United States, Ohio | |
VA Medical Center, Cleveland | |
Cleveland, Ohio, United States, 44106 | |
United States, South Carolina | |
Ralph H Johnson VA Medical Center, Charleston | |
Charleston, South Carolina, United States, 29401-5799 | |
United States, Texas | |
VA North Texas Health Care System, Dallas | |
Dallas, Texas, United States, 75216 | |
United States, Washington | |
VA Puget Sound Health Care System, Seattle | |
Seattle, Washington, United States, 98108 | |
United States, Wisconsin | |
Wlliam S. Middleton Memorial Veterans Hospital, Madison | |
Madison, Wisconsin, United States, 53705 | |
Puerto Rico | |
VA Medical Center, San Juan | |
San Juan, Puerto Rico, 00921 |
Study Chair: | Maurice Dysken | Minneapolis Veterans Affairs Medical Center |
Other Publications:
Responsible Party: | US Department of Veterans Affairs |
ClinicalTrials.gov Identifier: | NCT00235716 |
Other Study ID Numbers: |
546 |
First Posted: | October 10, 2005 Key Record Dates |
Results First Posted: | January 29, 2014 |
Last Update Posted: | July 23, 2014 |
Last Verified: | July 2014 |
Alzheimer's Disease clinical trial randomized controlled trial alpha-tocopherol |
vitamin E Namenda memantine |
Alzheimer Disease Brain Diseases Central Nervous System Diseases Nervous System Diseases Neurodegenerative Diseases Neurocognitive Disorders Mental Disorders Dementia Tauopathies Vitamins Vitamin E Tocopherols Tocotrienols |
alpha-Tocopherol Memantine Micronutrients Physiological Effects of Drugs Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Antiparkinson Agents Anti-Dyskinesia Agents Dopamine Agents Neurotransmitter Agents Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents |