Clinical trial NCT00000173 (phase 3, status: completed)
Conditions: alzheimer disease
ICD codes: G30.8, G30.9, G30.0, G30.1
Drugs: donepezil, vitamin e
SMILES: O=S(=O)(C1=CC=CC=C1)C1=CN=C2C(C=CC=C2N2CCNCC2)=C1, CC(C)CCC[C@@H](C)CCC[C@@H](C)CCC[C@]1(C)CCC2=C(O1)C(C)=C(C)C(O)=C2C
Eligibility criteria:

        Inclusion Criteria:

          -  Memory complaints and memory difficulties which are verified by an informant.

          -  Abnormal memory function documented by scoring below the education adjusted cutoff on
             the Logical Memory II subscale (Delayed Paragraph Recall) from the Wechsler Memory
             Scale - Revised (the maximum score is 25): a) less than or equal to 8 for 16 or more
             years of education, b) less than or equal to 4 for 8-15 years of education, c) less
             than or equal to 2 for 0-7 years of education.

          -  Mini-Mental Exam score between 24 and 30 (inclusive) (Exceptions may be made for
             subjects with less than 8 years of education at the discretion of the project
             director.).

          -  Clinical Dementia Rating = 0.5. Memory Box score must be at least 0.5.

          -  General cognition and functional performance sufficiently preserved such that a
             diagnosis of Alzheimer's disease cannot be made by the site physician at the time of
             the screening visit.

          -  No significant cerebrovascular disease: Modified Hachinski score of less than or equal
             to 4.

          -  Age between 55 and 90 (inclusive).

          -  Permitted medications stable for at least 1 month prior to screening. In particular:
             a) Subjects may take stable doses of antidepressants lacking significant
             anticholinergic side effects (if they are not currently depressed and do not have a
             history of major depression within the past 2 years). b) Estrogen replacement therapy
             is permissible. c) Ginkgo biloba is permissible, but discouraged.

          -  Hamilton Depression rating scale score of less than or equal to 12 on the 17-item
             scale.

          -  Informant is available who has frequent contact with the subject (e.g. an average of
             10 hours per week or more), agrees to monitor administration of study drug, observe
             for adverse events, and accompany the subject to all clinic visits for the duration of
             the protocol.

          -  CT or MRI scans within 12 months prior to screening without evidence of infection,
             infarction, or other focal lesions and without clinical symptoms suggestive of
             intervening neurological disease. A lacune in a non-critical brain area which is not
             believed to contribute to the subject's cognitive impairment is permissible.

          -  Adequate visual and auditory acuity to allow neuropsychological testing.

          -  Good general health with no additional diseases expected to interfere with the study.

          -  Normal B12, RPR, and Thyroid Function Tests or without any clinically significant
             abnormalities that would be expected to interfere with the study.

          -  ECG without clinically significant abnormalities that would be expected to interfere
             with the study.

          -  Subject is not pregnant, lactating, or of childbearing potential (i.e. women must be
             two years post-menopausal or surgically sterile).

          -  Agreement not to take other vitamin supplements (including Vitamin E), multivitamins,
             other than those provided by the study.

        Exclusion Criteria:

          -  Any significant neurologic disease other than suspected incipient Alzheimer's disease,
             such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal
             pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder,
             subdural hematoma, multiple sclerosis, or history of significant head trauma followed
             by persistent neurologic defaults or known structural brain abnormalities.

          -  Major depression or another major psychiatric disorder as described in DSM IV within
             the past 2 years.

          -  Psychotic features, agitation or behavioral problems within the last 3 months which
             could lead to difficulty complying with the protocol.

          -  History of alcohol or substance abuse or dependence within the past 2 years (DSM IV
             criteria).

          -  History of schizophrenia (DSM IV criteria).

          -  Any significant systemic illness or unstable medical condition which could lead to
             difficulty complying with the protocol including: a) History of systemic cancer within
             the last 5 years (non-metastatic skin cancers are acceptable). b) History of
             myocardial infarction within the past year or unstable or severe cardiovascular
             disease including angina or CHF with symptoms at rest. c) Clinically significant
             obstructive pulmonary disease or asthma. d) Clinically significant and unstable
             gastrointestinal disorder such as ulcer disease or a history of active or occult
             gastrointestinal bleeding within two years. e) Clinically significant laboratory test
             abnormalities on the battery of screening tests (hematology, prothrombin time,
             chemistry, urinalysis, ECG). f) Insulin-requiring diabetes or uncontrolled diabetes
             mellitus. g) Uncontrolled hypertension (systolic BP greater than 170 or diastolic
             greater than 100). h) History of clinically significant liver disease, coagulopathy,
             or vitamin K deficiency within the past 2 years.

          -  Medications a) Use of centrally active beta-blockers, narcotics, methyldopa and
             clonidine within 4 weeks prior to screening. b) Use of anti-Parkinsonian medications
             (e.g. Sinemet, amantadine, bromocriptine, pergolide and selegiline) within 2 months
             prior to screening. c) Use of neuroleptics or narcotic analgesics within 4 weeks prior
             to screening. d) Use of long-acting benzodiazepines or barbituates within 4 weeks
             prior to screening. e) Use of short-acting anxiolytics or sedative hypnotics more
             frequently than 2 times per week within 4 weeks prior to screening (note: sedative
             agents should not be used within 72 hours of screening).

             f) Initiation or change in dose of an antidepressant lacking significant cholinergic
             side effects within the 4 weeks prior to screening (use of stable doses of
             antidepressants for at least 4 weeks prior to screening is acceptable). g) Use of
             systemic corticosteroids within 3 months prior to screening. h) Medications with
             significant cholinergic or anticholinergic side effects (e.g. pyridostigmine,
             tricyclic antidepressants, meclizine, and oxybutynin) within 4 weeks prior to
             screening. i) Use of anti-convulsants (e.g. Phenytoin, Phenobarbital, Carbamazepine)
             within 2 months prior to screening. j) Use of warfarin (Coumadin) within 4 weeks prior
             to screening.

          -  Vitamin Supplements a) Use of vitamin supplements other than standard multivitamin
             included as part of the treatment intervention used in this protocol within 2 weeks
             prior to screening.

          -  Any prior use of any FDA approved medications for the treatment of Alzheimer's disease
             (e.g. tacrine, donepezil, or other newly approved medications).

          -  Use of any investigational drugs within 30 days or 5 half-lives, whichever is longer,
             prior to screening.

          -  Subjects who, in the investigator's opinion, will not comply with study procedures.