Alzheimer's Disease
Conditions
Keywords
Alzheimer's Disease, bryostatin 1, bryostatin, safety, efficacy, pharmacokinetics, pharmacodynamics, protein kinase C
Brief 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.
Interventions
DRUGBryostatin for Injection
A single one-hour intravenous infusion of 10 or 15 ug/m2 Bryostatin for Injection on Day 1
DRUGPlacebo
A single one-hour intravenous infusion of placebo on Day 1
Sponsors
Blanchette Rockefeller Neurosciences Insitute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse Events | 4-weeks |
| Alzheimer's Disease Assessment Scale | 4-weeks post dose |
| Clinician's Interview Based Impression of Change | 4-weeks post dose |
Secondary
| Measure | Time frame |
|---|---|
| Alzheimer's Disease Assessment Scale | 24, 48, and 72 hrs post dose |
| Clinician's Interview Based Impression of Change | 24, 48, and 72 hrs post dose |
| Clinical Dementia Rating Battery | 24, 48, and 72 hrs post dose and 4-weeks post dose |
| Alzheimer's Disease Cooperative Study - Activities of Daily Living | 24, 48, and 72 hrs post dose and 4-weeks post dose |
| Respiratory rate | 48 hrs and 4-weeks post dose |
| Blood pressure | 15, 30, and 60 minutes after start of study drug infusion, and at 1, 2, 4, 8, 12, 24, 48, and 72 hrs post infusion and 4-weeks post infusion |
| Heart rate | 15, 30, and 60 minutes after start of study drug infusion, and at 1, 2, 4, 8, 12, 24, 48, and 72 hrs post infusion and 4-weeks post infusion |
| Severe Impairment Battery | 24, 48, and 72 hrs post dose and 4-weeks post dose |
| Physical Exam | 48 hrs and 4-weeks post dose |
| Hematology | 48 hrs and 4-weeks post dose |
| Blood chemistry | 48 hrs and 4-weeks post dose |
| Urinalysis | 48 hrs and 4-weeks post dose |
| Pharmacokinetics | Blood draws at baseline, during the study drug infusion (15, 30, and 60 minutes after start of infusion), and at 20 minutes, 1 hr, 2 hrs, 6 hrs, 24 hrs, 48 hrs, and 72 hrs post infusion |
| Protein kinase C activity (pharmacodynamics) | Blood draws at baseline, during the study drug infusion (15, 30, and 60 minutes after start of infusion), and at 20 minutes, 1 hr, 2 hrs, 6 hrs, 24 hrs, 48 hrs, and 72 hrs post infusion |
| Electrocardiogram | 15, 30, and 60 minutes after start of study drug infusion, and at 1, 2, 4, 8, 12, and 24 hrs post infusion and 4-weeks post infusion |
| Hopkins Verbal Learning Test-Revised | 24, 48, and 72 hrs post dose and 4-weeks post dose |
| Temperature | 48 hrs and 4-weeks post dose |
Countries
United States
Outcome results
None listed