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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):
VA Office of Research and Development
ClinicalTrials.gov Identifier:
NCT00235716
First received: October 6, 2005
Last updated: July 14, 2014
Last verified: July 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 
Overall Participants Analyzed 
[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 
[1] Data collected through genetic sub-study with separate informed consent.
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 [1] 
[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] Higher the level the more dependence / less independence.


  Outcome Measures
  Show All Outcome Measures

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


  Limitations and Caveats
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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.


  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.


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 of Results:
Other Publications:

Responsible Party: VA Office of Research and Development
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: July 14, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration