Clinical trial NCT00606164: Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics Study of Bryostatin 1 in Patients With Alzheimer's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Alzheimer's Disease
Keywords: Alzheimer's Disease
bryostatin 1
bryostatin
safety
efficacy
pharmacokinetics
pharmacodynamics
protein kinase C
Lead sponsor: Blanchette Rockefeller Neurosciences Insitute
Sponsor class: OTHER
First posted: 2008-02-01
Enrollment: 9
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Adverse Events
timeFrame: 4-weeks
measure: Alzheimer's Disease Assessment Scale
timeFrame: 4-weeks post dose
measure: Clinician's Interview Based Impression of Change
timeFrame: 4-weeks post dose
Secondary outcomes:
measure: Alzheimer's Disease Assessment Scale
timeFrame: 24, 48, and 72 hrs post dose
measure: Clinician's Interview Based Impression of Change
timeFrame: 24, 48, and 72 hrs post dose
measure: Clinical Dementia Rating Battery
timeFrame: 24, 48, and 72 hrs post dose and 4-weeks post dose
measure: Alzheimer's Disease Cooperative Study - Activities of Daily Living
timeFrame: 24, 48, and 72 hrs post dose and 4-weeks post dose
measure: Severe Impairment Battery
timeFrame: 24, 48, and 72 hrs post dose and 4-weeks post dose
measure: Hopkins Verbal Learning Test-Revised
timeFrame: 24, 48, and 72 hrs post dose and 4-weeks post dose
measure: Temperature
timeFrame: 48 hrs and 4-weeks post dose
measure: Respiratory rate
timeFrame: 48 hrs and 4-weeks post dose
measure: Blood pressure
timeFrame: 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
measure: Heart rate
timeFrame: 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
measure: Electrocardiogram
timeFrame: 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
measure: Physical Exam
timeFrame: 48 hrs and 4-weeks post dose
measure: Hematology
timeFrame: 48 hrs and 4-weeks post dose
measure: Blood chemistry
timeFrame: 48 hrs and 4-weeks post dose
measure: Urinalysis
timeFrame: 48 hrs and 4-weeks post dose
measure: Pharmacokinetics
timeFrame: 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
measure: Protein kinase C activity (pharmacodynamics)
timeFrame: 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
Other outcomes:
Locations:
city: Morgantown
country: United States
facility: Chestnut Ridge Center West Virginia University Department of Behavioral Medicine and Psychiatry
state: West Virginia
Study officials:
affiliation: West Virginia University Department of Behavioral Medicine and Psychiatry
name: James M Stevenson, MD
role: PRINCIPAL_INVESTIGATOR
References: