A Study Assessing Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease
- Registration Number
- NCT02431468
- Lead Sponsor
- Neurotrope Bioscience, Inc.
- Brief Summary
This is a randomized double-blind placebo-controlled study comparing different doses of bryostatin for the treatment of moderately severe to severe Alzheimer's disease. The study is 15 weeks in duration, including a safety and efficacy evaluation 30 days after the last dose of study drug.
- Detailed Description
This study will enroll 150 moderately severe to severe Alzheimer's disease subjects. Subjects will be randomly assigned 1:1:1 to treatment with two different doses of bryostatin 1 or placebo. The primary analysis will take place after 12 weeks of treatment (7 doses).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 147
- Written informed consent from caregiver and subject (if possible) or legally acceptable representative if different from caregiver
- Male and female subjects 55-85 years of age inclusive
- Cognitive deficit present for at least 2 years that meet the diagnostic criteria for probable Alzheimer's
- Mini Mental State Exam (MMSE-2) score of 4-15
- Patients must be able to perform at least one item on the Severe Impairment Battery Scale
- Neuroimaging (computerized tomography (CT) or Magnetic Resonance Imaging (MRI)) within the last 24 months consistent with a diagnosis of probable Alzheimer's disease (AD)
- Reliable caregiver(s) or informant(s) who attends the subject at least an average of 3 hours or more per day for 3 or more days per week
- Adequate vision and motor function to comply with testing
- If taking drugs approved for treatment of Alzheimer's disease (e.g. cholinesterase inhibitors, memantine), must be on a stable dose for at least 3 months prior to entry into study and the dose must not change during the study unless a change is required due to an adverse event or a clinically significant change in the patient's status.
- Dementia due to any condition other than AD, including vascular dementia (Rosen-modified Hachinski lschemic score ≥ 5)
- Evidence of significant central nervous system (CNS) vascular disease on previous neuroimaging including but not limited to: cortical stroke, multiple infarcts, localized single infarcts in the thalamus, angular gyrus, multiple lacunar infarcts or extensive white matter injury
- Clinically significant neurologic disease or condition other than AD, such as cerebral tumor, chronic subdural fluid collections, Huntington's Disease, Parkinson's Disease, normal pressure hydrocephalus, or any other diagnosis that could interfere with assessment of safety and efficacy
- Evidence of clinically significant unstable cardiovascular, pulmonary, renal, hepatic, gastrointestinal, neurologic, or metabolic disease within the 6 months prior to enrollment
- Poorly controlled diabetes, at the discretion of the Principal Investigator
- Creatinine clearance (CL) of <45ml/min
- Use of an active Alzheimer's vaccine within 2 years prior to screening
- Use of a monoclonal antibody for treatment of AD within 1 year prior to screening
- Any medical or psychiatric condition that is likely to require initiation of additional medication or surgical intervention during the course of the study
- Use of an investigational drug within 30 days prior to screening
- Prior exposure to bryostatin, or known sensitivity to bryostatin or any ingredient in the study drug
- Any other concurrent medical condition, which in the opinion of the PI makes the subject unsuitable for the clinical study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo administered IV over 45 minutes every other week after 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1 40ug Bryostatin 1 Bryostatin 40 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 48 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1 20ug Bryostatin 1 Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks.
- Primary Outcome Measures
Name Time Method Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events Baseline through 30 days post end of treatment (up to Day 107) Evaluations of adverse events (AEs), serious adverse events (SAEs), Adverse event of special interest - myalgia
Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS) Primary analysis at Week 13 (day 91) after 12 weeks of treatment (up to day 107) The primary statistical objective for efficacy was to estimate the effect of bryostatin on the mean change in the total SIB score after 12 weeks of treatment, assessed at Week 13 (day 91). Efficacy analyses were conducted according to randomized groups. The SIB is used to assess cognition in subjects with moderate and severe AD. It is divided into nine subscales that include attention, language, orientation, memory, praxis, visuospatial ability, construction, social skills, orienting head to name. Non-verbal responses are allowed, thus decreasing the need for language output. Forty questions are included with a point score range of 0-100. Lower scores indicate greater cognitive impairment.
- Secondary Outcome Measures
Name Time Method Secondary Efficacy Endpoints Week 5, Week 9, Week 13 * Change from baseline in the Severe Impairment Battery (SIB) at Weeks 5 and 9. Assesses cognition. Score range 0-100. Lower scores indicate greater cognitive impairment.
* Change from baseline in Alzheimer Disease Cooperative Study Activities of Daily Living Inventory-Severe Impairment Version (ADCS-ADL-SEV) at Weeks 5, 9,13. A 19-item test of the performance of activities of daily living. Total score range 0-54; lower scores indicate greater functional impairment.
* Change from baseline in MMSE-2 at Weeks 5, 9 and 13. Tests selected aspects of cognition on a scale of 0-30. Lower scores indicate greater cognitive impairment.
* Change from baseline in Neuropsychiatric Inventory (NPI) at Weeks 5, 9,13. Caregiver interview assesses 12 behavioral disturbances. Scores range from 0-144; higher scores indicate greater behavioral disturbances.
* Clinical Global Impression of Improvement (CGI-I) at Weeks 5, 9, 13. A 7-point scale range from (1) very much improved to (7) very much worse.
Trial Locations
- Locations (29)
Atlanta Center for Medical Research
🇺🇸Atlanta, Georgia, United States
J. Gary Booker, MD APMC Clinical Drug Trials
🇺🇸Shreveport, Louisiana, United States
University of Kansas Alzheimer's Disease Center
🇺🇸Fairway, Kansas, United States
ATP Clinical Research, Inc.
🇺🇸Costa Mesa, California, United States
Nader Pharmacology Research Institute
🇺🇸Los Alamitos, California, United States
Alzheimer's Research and Treatment Center
🇺🇸Lake Worth, Florida, United States
San Francisco Clinical Research Center
🇺🇸San Francisco, California, United States
Xenoscience, Inc/ 21st Century Neurology
🇺🇸Phoenix, Arizona, United States
Miami Jewish Health System
🇺🇸Miami, Florida, United States
Alexian Brothers Neurosciences Institute Clinical Research
🇺🇸Elk Grove Village, Illinois, United States
JEM Research
🇺🇸Atlantis, Florida, United States
Brain Matters Research
🇺🇸Delray Beach, Florida, United States
Neuropsychiatric Research Center of South Florida
🇺🇸Fort Myers, Florida, United States
Medical Research Group of Central Florida
🇺🇸Orange City, Florida, United States
Compass Research, LLC
🇺🇸Orlando, Florida, United States
Axiom Clinical Research of Florida
🇺🇸Tampa, Florida, United States
Compass Research
🇺🇸The Villages, Florida, United States
iResearch Atlanta
🇺🇸Decatur, Georgia, United States
Atlantic Neuroscience Institute
🇺🇸Springfield, New Jersey, United States
Millennium Psychiatric Associates
🇺🇸Creve Coeur, Missouri, United States
Neurological Associates of Albany, PC
🇺🇸Albany, New York, United States
Alzheimer's Memory Center
🇺🇸Charlotte, North Carolina, United States
Parker Jewish Institute for Health Care and Rehabilitation
🇺🇸New Hyde Park, New York, United States
Neurobehavioral Clinical Research
🇺🇸Canton, Ohio, United States
Oklahoma Clinical Research Center
🇺🇸Oklahoma City, Oklahoma, United States
Sunstone Clinical Research
🇺🇸Medford, Oregon, United States
The Clinical Trial Center, LLC
🇺🇸Jenkintown, Pennsylvania, United States
Neurology Clinic, PC
🇺🇸Cordova, Tennessee, United States
Lake Charles Clinical Trials
🇺🇸Lake Charles, Louisiana, United States