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.

Study Overview

• Status: Unknown
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo; Drug: Bryostatin for Injection

• Study Type: Interventional
• Enrollment (Anticipated): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Chestnut Ridge Center West Virginia University Department of Behavioral Medicine and Psychiatry
      • Contact: Eric Rankin, Ph.D.; Phone Number: 304-293-5323; Email: erankin@hsc.wvu.edu
      • Principal Investigator: James M Stevenson, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; A single one-hour intravenous infusion of placebo on Day 1; Other Names: PET (60/30/10) diluent plus sodium chloride for injection
Experimental: 10 ug/m2 Bryostatin	Drug: Bryostatin for Injection; A single one-hour intravenous infusion of 10 or 15 ug/m2 Bryostatin for Injection on Day 1; Other Names: Bryostatin; Bryostatin 1; NSC 339555; CAS No. 83314-01-6
Experimental: 15 ug/m2 Bryostatin	Drug: Bryostatin for Injection; A single one-hour intravenous infusion of 10 or 15 ug/m2 Bryostatin for Injection on Day 1; Other Names: Bryostatin; Bryostatin 1; NSC 339555; CAS No. 83314-01-6

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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
Severe Impairment Battery	24, 48, and 72 hrs post dose and 4-weeks post dose
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
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
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
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

Collaborators and Investigators

• Sponsor: Blanchette Rockefeller Neurosciences Insitute
• Investigators: Principal Investigator: James M Stevenson, MD, West Virginia University Department of Behavioral Medicine and Psychiatry

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Anticipated): December 1, 2008
• Study Completion (Anticipated): December 1, 2008

Study Registration Dates

• First Submitted: January 21, 2008
• First Submitted That Met QC Criteria: January 21, 2008
• First Posted (Estimate): February 1, 2008

Study Record Updates

• Last Update Posted (Estimate): February 1, 2008
• Last Update Submitted That Met QC Criteria: January 21, 2008
• Last Verified: January 1, 2008

More Information

Terms related to this study

• Keywords: safety; Alzheimer's Disease; pharmacokinetics; efficacy; pharmacodynamics; bryostatin; bryostatin 1; protein kinase C
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Bryostatin 1
• Other Study ID Numbers: BRY-201