safety, efficacy, pharmacokinetics, and pharmacodynamics study of bryostatin 1 in patients with alzheimer's disease

Conditions: Alzheimer's Disease

Summary: the main purpose of this study is find out how safe a single dose of bryostatin 1 is in patients with alzheimer's disease (ad). this study is also being done 1) to determine how effective a single dose of bryostatin 1 is in the treatment of ad, 2) to find out what happens to bryostatin 1 once it enters the body by measuring the levels of bryostatin 1 in blood, and 3) to measure a substance in the blood (protein kinase c) that may help to better understand how bryostatin 1 works.


Eligibility criteria:
inclusion criteria: * male or female, age 50 yrs or older. females must be of non-childbearing potential (surgically sterilized or at least 2 yrs post-menopausal) * must have a cognitive deficit present for at least 1 yr \& meet dsm-iv-trtm criteria for ad \& meet nincds/adrda criteria for the presence of probable ad * severity of ad must be mild to moderate, documented with a mmse score of 12-26 * has a ct scan or mri scan within the prior 12 months, which is compatible with a diagnosis of probable ad * ability to walk, at least with an assistive device * vision \& hearing sufficient to comply with testing * normal cognitive \& social functioning prior to onset of dementia * consistent caregiver to accompany patient to assessment visits * sufficient basic education to be able to complete the cognitive assessments * living outside an institution * informed consent signed \& dated by patient or legal representative * has provided written authorization for the use \& disclosure of protected health information exclusion criteria: * dementia due to any condition other than ad, including vascular dementia (modified hachinski ischemic scale ≥ 5; positive ninds-airen criteria) * evidence of clinically significant unstable cardiovascular, renal, hepatic, gastrointestinal, neurological, or metabolic disease within the past 6 months (as determined by medical history, ecg results, chest x-ray, or physical examination) * use of any drug within 14 days prior to randomization unless the dose of the drug \& the condition being treated have been stable for at least 30 days \& are expected to remain stable during the study \& neither the drug nor the condition being treated is expected to interfere with the study endpoints * any medical or psychiatric condition that may require medication or surgical treatment during the study * life expectancy less than 6 months * any other screening laboratory values outside the normal ranges that are deemed clinically significant by the investigator * use of an investigational drug within 30 days prior to the screening visit or during the entire study * significant neurological disease other than ad, including cerebral tumor, huntington's disease, parkinson's disease, normal pressure hydrocephalus, \& other entities * major depression according to dsm-iv * psychotic episodes requiring hospitalization or antipsychotic therapy for more than 2 weeks within the past 10 yrs, not linked to ad * agitation sufficient to preclude participation in this trial * alcohol or drug dependence diagnosed within the past 10 yrs * epilepsy or anti-epileptic drug therapy * abnormal laboratory tests that might point to another etiology for dementia: serum b12, folate, thyroid functions, electrolytes, syphilis serology * musculoskeletal diseases that could interfere with assessment * acute or poorly controlled medical illness: blood pressure\> 180 mmhg systolic or 100 mmhg diastolic; myocardial infarction within 6 months; uncompensated congestive heart failure (nyha class iii or iv), severe renal, hepatic or gastrointestinal disease that could alter drug pharmacokinetics; blood glucose \> 180 mg/dl on repeated testing at entry into study or need for insulin therapy * previous randomization in this trial or participation in another investigational trial \< 2 months prior to randomization * likelihood, according to clinical judgment, of being transferred to a nursing home within 6 months * change in dosage of any concomitant antidepressant within 30 days prior to randomization * lack of caregiver * pregnant or lactating females * patients who in the judgment of the investigator may be unreliable or uncooperative with the evaluation procedures outlined in this protocol * hiv positive * hepatitis b or c positive * concomitant use of medications other than ad or antidepressant medications for which the dose regimens are stabilized for at least 30 days prior to enrollment in study

Keywords: alzheimer's disease bryostatin 1 bryostatin safety efficacy pharmacokinetics pharmacodynamics protein kinase c