Nefiracetam in the Treatment of Alzheimer's Disease

You may be eligible if

• Study subjects will satisfy NINCDS-ADRDA criteria for probable AD. Dementia severity will be in the mild to moderate range, as evidenced by a Mini-Mental State Examination total score of 12-25 which is roughly equivalent to Alzheimer's Disease Assessment Scale Cognitive (ADAS-Cog) scores of 30 to 11, will include deficits in at least 2 areas of cognition, will have been present at least 1 year, and will have progressed gradually since onset. Patients must be between the ages of 50-90 with onset of dementia after age 40. The modified Hachinski Ischemia Score must be less than 4 and the brain MRI within 2 years of enrollment must be consistent with the diagnosis of AD.
• Patients must have had a brain MRI since the onset of dementia symptoms that is consistent with the diagnosis of AD.
• Patients must have an acceptable nutritional status (i.e., body weight within 20% of desirable weight for height).
• Patients must be surgically sterile.
• Patients must be post-menopausal or practicing adequate contraception.
• Physical and laboratory exams must be normal, or the abnormalities must be attributed to the dementing illness or judged clinically unimportant to the safe conduct of this trial.
• Chest X-ray within 1 year of enrollment must show no active disease.
• No history or clinical diagnosis of stroke within 1 year before or concurrent with onset of dementia; hydrocephalus, subdural hematoma, or mass lesion on screening MRI; current seizure disorder; head trauma with loss of consciousness and hospitalization within 1 year before or concurrent with onset of dementia; dementia onset within 1 year following cardiac arrest or surgery; Parkinson's disease (onset prior to or concurrent with dementia), Wilson's, Huntington's, Creutzfeldt-Jakob disease, Pick's disease, or Wernicke's encephalopathy; chronic CNS infection (positive RPR and/or FTA-ABS acceptable if luetic brain disease excluded by documented studies and/or treatment).
• No COPD or asthma requiring hospital treatment within 1 year before enrollment (treatment of acute respiratory infections is acceptable).
• No acute systemic infection.
• No hypothyroidism (TSH greater than 6.0 mclU/ml).
• No folic acid (less than 0.9 ng/ml) or B12 deficiency (less than 100 pg/ml) within 1 year before study enrollment.
• No recent or acute HAV or HBV infection, or chronic HBV infection by immuno-assays.
• No insulin dependent diabetes or poorly controlled non-insulin dependent diabetes.
• No history of leukopenia, neutropenia, or thrombocytopenia, cancer (except treated, non-recurrent skin cancer) within 2 years before enrollment.
• No severe renal insufficiency (Clcr less than 25 ml/min, BUN greater than 30 mg/dl, or creatinine greater than 2.0 mg/dl), hepatic insufficiency (as indicated by: ASAT (SGOT) 3 x ULN, ALAT (SGPT) 3 x ULN, or total bilirubin greater than 2.0 mg/dl).
• No homocysteinemia (greater than 14 micromol/L).
• No past history of schizophrenia.
• No substance use disorder within 1 year of dementia onset.
• No depression requiring medical treatment within the past 30 days.
• No administration of tacrine (Cognex) or donezepil (Aricept), investigational drugs, or nutritional supplements used as neurotransmitter precursors for cognitive enhancement within 30 days before enrollment.
• No use of anticonvulsants, psychostimulants, centrally acting anticholinergics and agents known to inhibit or be metabolized by CYP 3A4 (e.g., erythromycin, chlarythromycin, troleandomycin, fluconazole, miconazole, ketoconazole, itraconazole and grapefruit juice) within 2 weeks prior to enrollment.
• No hepatic, cardiovascular, gastrointestinal, or hematological illness which could interfere with drug absorption, distribution, metabolism, or excretion.
• No medical condition that contraindicates cholinergics.
• No known hypersensitivity to nefiracetam.
• Must be able to swallow/retain tablets.
• No history of medical noncompliance.
• Must have significant other person or caregiver to assure compliance.
• No uncorrectable loss of hearing or eyesight that precludes psychometric testing.
• Ability to comprehend instructions or respond to test items of the ADAS and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) during baseline administration.
• No male patients interested in conceiving children given the potential adverse effects on spermatogenesis.