A Randomized, Clinical Trial of Vitamin E and Memantine in Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: dl-alpha-tocopherol; Memantine; dl-alpha-tocopherol; Memantine; Placebo
Intervention description: 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.; 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.; 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.; 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.; Matching placebos for dl-alpha-tocopherol and memantine.
Intervention MeSH terms: Vitamins; Vitamin E; Tocopherols; Tocotrienols; alpha-Tocopherol; Memantine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 613.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: Alzheimer's Disease; clinical trial; randomized controlled trial; alpha-tocopherol; vitamin E; Namenda; memantine

Summary:

      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.
    

Eligibility 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