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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2008 by Blanchette Rockefeller Neurosciences Insitute.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
Blanchette Rockefeller Neurosciences Insitute
ClinicalTrials.gov Identifier:
NCT00606164
First received: January 21, 2008
Last updated: NA
Last verified: January 2008
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Alzheimer's Disease
Drug: Bryostatin for Injection
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Blanchette Rockefeller Neurosciences Insitute:

Primary Outcome Measures:
  • Adverse Events [ Time Frame: 4-weeks ] [ Designated as safety issue: Yes ]
  • Alzheimer's Disease Assessment Scale [ Time Frame: 4-weeks post dose ] [ Designated as safety issue: No ]
  • Clinician's Interview Based Impression of Change [ Time Frame: 4-weeks post dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Alzheimer's Disease Assessment Scale [ Time Frame: 24, 48, and 72 hrs post dose ] [ Designated as safety issue: No ]
  • Clinician's Interview Based Impression of Change [ Time Frame: 24, 48, and 72 hrs post dose ] [ Designated as safety issue: No ]
  • Clinical Dementia Rating Battery [ Time Frame: 24, 48, and 72 hrs post dose and 4-weeks post dose ] [ Designated as safety issue: No ]
  • Alzheimer's Disease Cooperative Study - Activities of Daily Living [ Time Frame: 24, 48, and 72 hrs post dose and 4-weeks post dose ] [ Designated as safety issue: No ]
  • Severe Impairment Battery [ Time Frame: 24, 48, and 72 hrs post dose and 4-weeks post dose ] [ Designated as safety issue: No ]
  • Hopkins Verbal Learning Test-Revised [ Time Frame: 24, 48, and 72 hrs post dose and 4-weeks post dose ] [ Designated as safety issue: No ]
  • Temperature [ Time Frame: 48 hrs and 4-weeks post dose ] [ Designated as safety issue: Yes ]
  • Respiratory rate [ Time Frame: 48 hrs and 4-weeks post dose ] [ Designated as safety issue: Yes ]
  • Blood pressure [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  • Heart rate [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  • Electrocardiogram [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  • Physical Exam [ Time Frame: 48 hrs and 4-weeks post dose ] [ Designated as safety issue: Yes ]
  • Hematology [ Time Frame: 48 hrs and 4-weeks post dose ] [ Designated as safety issue: Yes ]
  • Blood chemistry [ Time Frame: 48 hrs and 4-weeks post dose ] [ Designated as safety issue: Yes ]
  • Urinalysis [ Time Frame: 48 hrs and 4-weeks post dose ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Protein kinase C activity (pharmacodynamics) [ Time Frame: 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 9
Study Start Date: April 2008
Estimated Study Completion Date: December 2008
Estimated Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
A single one-hour intravenous infusion of placebo on Day 1
Other Name: 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 1
  • Bryostatin
  • 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 1
  • Bryostatin
  • NSC 339555
  • CAS No. 83314-01-6

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00606164

Locations
United States, West Virginia
Chestnut Ridge Center West Virginia University Department of Behavioral Medicine and Psychiatry Not yet recruiting
Morgantown, West Virginia, United States, 26505
Contact: Eric Rankin, Ph.D.    304-293-5323    erankin@hsc.wvu.edu   
Principal Investigator: James M Stevenson, MD         
Sponsors and Collaborators
Blanchette Rockefeller Neurosciences Insitute
Investigators
Principal Investigator: James M Stevenson, MD West Virginia University Department of Behavioral Medicine and Psychiatry
  More Information

No publications provided

Responsible Party: Mark A. Cochran, Ph.D./CEO and Executive Director, Blanchette Rockefeller Neurosciences Insitute
ClinicalTrials.gov Identifier: NCT00606164     History of Changes
Other Study ID Numbers: BRY-201
Study First Received: January 21, 2008
Last Updated: January 21, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by Blanchette Rockefeller Neurosciences Insitute:
Alzheimer's Disease
bryostatin 1
bryostatin
safety
efficacy
pharmacokinetics
pharmacodynamics
protein kinase C

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Dementia
Tauopathies
Bryostatin 1
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014