Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics Study of Bryostatin 1 in Patients With Alzheimer's Disease

A Randomized, Double-Blind, Placebo-Controlled, Parallel Groups, Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Bryostatin 1 in Patients With Mild to Moderate Alzheimer's Disease

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.

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