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
  Purpose

The purpose of this study is to determine whether alpha-tocopherol, memantine (Namenda), or the combination will significantly delay clinical progression in mild to moderately demented patients with Alzheimer's disease compared to placebo.


Condition Intervention Phase
Alzheimer's Disease
Drug: dl-alpha-tocopherol
Drug: Memantine
Drug: Placebo
Phase 3

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
Official Title: CSP #546 - A Randomized, Clinical Trial of Vitamin E and Memantine in Alzheimer's Disease (TEAM-AD)

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Dependence Scale: Time to Event Analysis (Increase of of One Dependence Level) [ Time Frame: Every 6 months to a maximum of 4 years ] [ Designated as safety issue: No ]
    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).


Other Outcome Measures:
  • All-cause Mortality [ Time Frame: up to 4 years ] [ Designated as safety issue: Yes ]
    Survival analysis of death from any cause.


Enrollment: 613
Study Start Date: August 2007
Study Completion Date: October 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
2,000 IU per day of dl-alpha-tocopherol plus placebo for memantine
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
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
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
Drug: Placebo
Matching placebos for dl-alpha-tocopherol and memantine.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnoses of possible or probable Alzheimer's disease (NINCDS-ADRDA)
  2. 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
  3. Written informed consent from both the patient (or surrogate) and caregiver
  4. An MMSE score between 12 and 26 inclusive
  5. 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
  6. 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:

  1. A non-Alzheimer primary dementia (e.g., vascular dementia, Lewy body dementia, fronto-temporal dementia, vitamin B-12 deficiency, hypothyroidism)
  2. Current major depression, delirium, alcohol or psychoactive substance abuse or dependency, schizophrenia, or delusional disorder as defined by DSM-IV
  3. Presence of any uncontrolled systemic illness that would interfere with participation in the study or a life expectancy of less than one year
  4. Pregnant or intention to become pregnant
  5. Enrollment in another interventional clinical trial
  6. Current prescription with more than one AChE inhibitor
  7. Current prescription for warfarin
  8. Use of vitamin E supplements in the past 2 weeks
  9. Use of memantine in the past 4 weeks or known intolerance
  10. Estimated creatinine clearance less than 5ml/min (Cockcroft-Gault formula)
  11. Use of amantadine in the past 2 weeks
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00235716

Locations
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
Sponsors and Collaborators
Forest Laboratories
DSM Nutritional Products, Inc.
Investigators
Study Chair: Maurice Dysken Minneapolis Veterans Affairs Medical Center
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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

Keywords provided by Department of Veterans Affairs:
Alzheimer's Disease
clinical trial
randomized controlled trial
alpha-tocopherol
vitamin E
Namenda
memantine

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Memantine
Vitamin E
Alpha-Tocopherol
Tocopherols
Tocotrienols
Vitamins
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Antioxidants
Protective Agents
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on July 09, 2014