A Randomized, Clinical Trial of Vitamin E and Memantine in Alzheimer's Disease (TEAM-AD)

This study has been completed.
Sponsor:
Collaborators:
Forest Laboratories
DSM Nutritional Products, Inc.
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00235716
First received: October 6, 2005
Last updated: January 23, 2014
Last verified: January 2014
Results First Received: December 6, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Factorial Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Alzheimer's Disease
Interventions: Drug: dl-alpha-tocopherol
Drug: Memantine
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment initiated in August, 2007 and concluded in March, 2012. Enrollment took place at 14 VA medical centers.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Vitamin E Alpha-tocopherol (vitamin E in the form of dl-alpha-tocopheryl acetate), 2000 international units (IU) per day, taken as one 1000 IU hard-gelatin, liquid-filled capsules twice a day plus matching memantine placebos.
Memantine (Namenda) Memantine 20 mg per day, titrated over four weeks to a maintenance dosage of 10 mg pills taken twice a day plus matching vitamin E placebo.
Vitamin E + Memantine 2000 IU of Alpha-tocopherol (vitamin E) per day plus 20 mg memantine per day.
Placebo Matching placebo pills for vitamin E and memantine

Participant Flow:   Overall Study
    Vitamin E     Memantine (Namenda)     Vitamin E + Memantine     Placebo  
STARTED     152     155     154     152  
COMPLETED     90     88     89     90  
NOT COMPLETED     62     67     65     62  
Death                 26                 39                 32                 31  
Withdrawal by Subject                 23                 19                 17                 18  
Lost to Follow-up                 12                 7                 14                 10  
Adverse Event                 1                 1                 1                 0  
Physician Decision                 0                 1                 1                 3  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Vitamin E Alpha-tocopherol (vitamin E in the form of dl-alpha-tocopheryl acetate), 2000 international units (IU) per day, taken as one 1000 IU hard-gelatin, liquid-filled capsules twice a day plus matching memantine placebos.
Memantine (Namenda) Memantine 20 mg per day, titrated over four weeks to a maintenance dosage of 10 mg pills taken twice a day plus matching vitamin E placebo.
Vitamin E + Memantine 2000 IU of Alpha-tocopherol (vitamin E) per day plus 20 mg memantine per day.
Placebo Matching placebo pills for vitamin E and memantine
Total Total of all reporting groups

Baseline Measures
    Vitamin E     Memantine (Namenda)     Vitamin E + Memantine     Placebo     Total  
Number of Participants  
[units: participants]
  152     155     154     152     613  
Age  
[units: years]
Mean ± Standard Deviation
  78.6  ± 7.2     78.8  ± 7.2     78.3  ± 7.0     79.4  ± 7.0     78.8  ± 7.1  
Gender  
[units: participants]
         
Female     6     6     4     3     19  
Male     146     149     150     149     594  
Ethnicity (NIH/OMB)  
[units: participants]
         
Hispanic or Latino     17     15     15     19     66  
Not Hispanic or Latino     135     140     139     133     547  
Unknown or Not Reported     0     0     0     0     0  
Race (NIH/OMB)  
[units: participants]
         
American Indian or Alaska Native     0     0     0     1     1  
Asian     0     1     0     0     1  
Native Hawaiian or Other Pacific Islander     0     1     0     0     1  
Black or African American     21     21     18     20     80  
White     130     132     136     131     529  
More than one race     1     0     0     0     1  
Unknown or Not Reported     0     0     0     0     0  
Region of Enrollment  
[units: participants]
         
United States     152     155     154     152     613  
Education  
[units: participants]
         
<High School Graduation     41     41     26     29     137  
High School Graduation     46     48     57     56     207  
Some College     27     38     37     33     135  
College Graduation or Advanced Degree     38     28     34     34     134  
Apolipoprotein E ε4 status [1]
[units: participants]
         
Non-carriers     47     48     59     55     209  
One ε4 allele     39     44     44     38     165  
Two ε4 alleles     10     13     8     10     41  
Not Tested     56     50     43     49     198  
Concomitant Medications Acetylcholinesterase Inhibitors (AChEI)  
[units: participants]
         
Donepezil     104     100     100     96     400  
Galantamine     43     47     49     55     194  
Rivastigmine     5     8     4     1     18  
None     0     0     1     0     1  
Weeks from AChEI Initiation to Randomization  
[units: participants]
         
≤ 12 weeks     46     36     49     37     168  
> 12 weeks     105     119     104     115     443  
Missing     1     0     1     0     2  
Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory  
[units: units on a scale]
Mean ± Standard Deviation
  56.6  ± 14.9     57.3  ± 14.2     56.4  ± 14.0     56.8  ± 13.7     56.8  ± 14.2  
Mini-Mental State Examination  
[units: units on a scale]
Mean ± Standard Deviation
  21.3  ± 3.3     20.8  ± 3.8     21.3  ± 3.4     20.8  ± 3.8     21.0  ± 3.6  
Alzheimer's Disease Assessment Scale - Cognitive portion  
[units: units on a scale]
Mean ± Standard Deviation
  18.5  ± 8.8     19.5  ± 7.9     18.0  ± 8.4     19.1  ± 8.4     18.8  ± 8.4  
Neuropsychiatric Inventory  
[units: units on a scale]
Mean ± Standard Deviation
  12.2  ± 13.3     12.1  ± 13.1     12.3  ± 13.3     13.5  ± 14.2     12.5  ± 13.4  
Caregiver Activity Survey  
[units: hours per day]
Mean ± Standard Deviation
  7.3  ± 14.3     6.7  ± 9.0     6.6  ± 10.5     6.5  ± 9.2     6.8  ± 10.9  
Dependence Scale [2]
[units: participants]
         
Level 0     5     6     8     3     22  
Level 1     8     6     8     5     27  
Level 2     85     91     80     79     335  
Level 3     31     35     31     37     134  
Level 4     4     7     10     8     29  
Level 5     19     10     17     20     66  
[1] Data collected through genetic sub-study with separate informed consent.
[2] Higher the level the more dependence / less independence.



  Outcome Measures
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1.  Primary:   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 ]

2.  Primary:   Mini-Mental State Examination Change From Baseline   [ Time Frame: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline ]

3.  Primary:   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 ]

4.  Primary:   Neuropsychiatric Inventory Change From Baseline   [ Time Frame: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline ]

5.  Primary:   Caregiver Activity Survey Change From Baseline   [ Time Frame: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline ]

6.  Secondary:   Dependence Scale: Time to Event Analysis (Increase of of One Dependence Level)   [ Time Frame: Every 6 months to a maximum of 4 years ]

7.  Other Pre-specified:   All-cause Mortality   [ Time Frame: up to 4 years ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Peter Guarino, PhD, Director WH-CSPCC
Organization: Dept. of Veterans Affairs Cooperative Stduies Program
phone: 203-932-5711 ext 3780
e-mail: peter.guarino@va.gov


Publications:
Publications automatically indexed to this study:

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00235716     History of Changes
Other Study ID Numbers: 546
Study First Received: October 6, 2005
Results First Received: December 6, 2013
Last Updated: January 23, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration