DHA (Docosahexaenoic Acid), an Omega 3 Fatty Acid, in Slowing the Progression of Alzheimer's Disease
- Conditions
- Alzheimer's Disease
- Interventions
- Drug: Placebo
- Registration Number
- NCT00440050
- Lead Sponsor
- Alzheimer's Disease Cooperative Study (ADCS)
- Brief Summary
The purpose of this study is to determine whether chronic DHA (Docosahexaenoic Acid) supplementation slows the progression of cognitive and functional decline in mild to moderate Alzheimer's disease (AD).
- Detailed Description
Preliminary studies have shown a reduced risk of Alzheimer's disease (AD) in people consuming increased amounts of fish in their diets. Many of the health benefits of fish are attributed to the abundance of omega 3 fatty acids. Docosahexaenoic Acid (DHA) is the most abundant omega 3 fatty acid in the brain. Data from several animal models supports the hypothesis that DHA may be an effective treatment for AD by means of anti-amyloid, antioxidant, and neuroprotectant mechanisms.
In this study, 400 individuals with mild to moderate AD will participate at approximately 53 study sites throughout the US for 18 months. Participants will be randomized so that 60% will receive approximately 2 grams of DHA, divided into 4 capsules, 2 capsules taken twice a day, while 40% receive an identical placebo.
Potential participants will go to their study site for a screening visit, where eligibility is determined, and if accepted, for a baseline visit where cognitive status, behavioral status, functional status, and global severity of dementia will be assessed. Vital signs and biomarker labs will also be obtained. Subsequent visits will occur every three months for medication checks and, every 6 months, further assessments, physical exams, and labs.
Some participants will also take part in MRI (magnetic resonance imaging) and/or CSF (cerebrospinal fluid) sub-studies. For the MRI sub-study, scans will be done prior to beginning the study medication, and again after 18 months. Likewise, for the CSF sub-study, a lumbar puncture will be done prior to beginning the study medication, and again after 18 months.
Enrollment is restricted to individuals who consume no more than 200 mg of DHA per day, which is almost 300% of the average daily intake in an American diet. Individuals who take fish oil or omega 3 fatty acid supplements are also not eligible. Each visit will include completion of a very brief food frequency questionnaire to monitor dietary DHA levels.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 402
- Male or female
- 50 years of age or older
- Residing in the community at baseline (includes assisted living facilities, but excludes long-term care nursing facilities)
- MMSE (Mini-Mental State Examination) at screen of 14-26 (inclusive)
- No medical contraindications to study participation
- Fluent in English or Spanish
- Corrected vision and hearing sufficient for compliance with testing procedures
- Supervision available for study medication
- Caregiver/study partner to accompany participant to all visits
- Study partner must have direct contact with the participant more than 2 days/week
- Able to ingest oral medication
- Daily DHA consumption less than or equal to 200 mg/day in prior two months estimated by an abbreviated DHA food frequency questionnaire
- Neuroimaging consistent with the diagnosis of AD at some time after the onset of the memory decline
- Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the investigator
- Stable use of cholinesterase inhibitors and memantine is permitted if doses are stable for 4 months prior to enrollment
- Non-AD dementia
- Residence in a long-term care facility at baseline
- History of clinically significant stroke
- Modified Hachinski Ischemia score ≥ 4
- Current evidence or history in past two years of epilepsy, seizure, focal brain lesion, head injury with loss of consciousness or DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
- Sensory impairment which would prevent subject from participating in or cooperating with the protocol
- Use of another investigational agent within two months
- Evidence of any significant clinical disorder or laboratory finding that renders the participant unsuitable for receiving an investigational new drug including clinically significant or unstable hematologic, hepatic, cardiovascular (including history of ventricular fibrillation or ventricular tachycardia), pulmonary, gastrointestinal, endocrine, metabolic, renal, or other systemic disease or laboratory abnormality
- Active neoplastic disease (skin tumors other than melanoma may be included; participants with stable prostate cancer may be included at the discretion of the Project Director)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1. DHA (Docosahexaenoic Acid) DHA 2. Placebo Placebo
- Primary Outcome Measures
Name Time Method Rate of Change on the ADAS-Cog 11. Baseline, 6, 12, 18 months ADAS-cog 11 = Alzheimer's Disease Assessment Scale, cognitive sub-scale in points per year. This is a psychometric measure sensitive to change in mild to moderate AD. The range of this instrument is 0 to 70 with higher numbers indicating greater impairment.
Rate of Change on CDR-SOB 18 months CDR-SOB = Clinical Dementia Rating, Sum of Boxes. This is a global rating of dementia severity based on the clinician's interpretation of the history and examination. The range of this instrument is 0 to 18 with higher numbers indicating greater impairment.
- Secondary Outcome Measures
Name Time Method Neuropsychiatric Inventory (NPI) 18 months The Neuropsychiatric Inventory quantifies behavioral changes in dementia, including depression, anxiety, psychosis, agitation, sleep change, appetite change, and others. This is a structured questionnaire administered to the subject's caregiver/study partner. The range of this instrument is 0 to 120 with higher numbers indicating greater impairment.
ADCS-ADL 18 months ADCS-ADL = Alzheimer's Disease Cooperative Study Activities of Daily Living Score. This is a structured questionnaire about activities of daily living, administered to the subject's caregiver/study partner. The range of this instrument is 0 to 6 with lower numbers indicating greater impairment.
Trial Locations
- Locations (51)
UCLA Neurology
🇺🇸Los Angeles, California, United States
Emory University Dept. of Psychiatry
🇺🇸Atlanta, Georgia, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
🇺🇸North Charleston, South Carolina, United States
Albany Medical College
🇺🇸Albany, New York, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
Banner Alzheimer's Institute
🇺🇸Phoenix, Arizona, United States
Mount Sinai School of Medicine
🇺🇸Bronx, New York, United States
Georgetown University Medical Center, Dept. of Neurology
🇺🇸Washington, District of Columbia, United States
Saint Mary's Health Care
🇺🇸Grand Rapids, Michigan, United States
Johns Hopkins University Division of Cognitive Neuroscience
🇺🇸Baltimore, Maryland, United States
University of California Irvine
🇺🇸Irvine, California, United States
Rhode Island Hospital Neurology
🇺🇸Providence, Rhode Island, United States
The Memory Clinic
🇺🇸Bennington, Vermont, United States
Northwestern University Cognitive Neurology and Alzheimer Disease Center
🇺🇸Chicago, Illinois, United States
Rush Alzheimer's Disease Center
🇺🇸Chicago, Illinois, United States
Sun Health Research Institute/Arizona Consortium
🇺🇸Sun City, Arizona, United States
UCSD Shiley-Marcos Alzheimer's Research Center
🇺🇸La Jolla, California, United States
Palo Alto Institute for Research & Education
🇺🇸Palo Alto, California, United States
Byrd Alzheimer's Institute
🇺🇸Tampa, Florida, United States
Howard University College of Medicine
🇺🇸Washington, District of Columbia, United States
Columbia University
🇺🇸New York, New York, United States
Washington University ADRC-Memory and Aging Project
🇺🇸St. Louis, Missouri, United States
University of Wisconsin Department of Medicine
🇺🇸Madison, Wisconsin, United States
New York University Medical Center
🇺🇸New York, New York, United States
University of Texas Southwestern-Memory Research Unit
🇺🇸Dallas, Texas, United States
University of Southern California Psychiatry and Behavioral Sciences
🇺🇸Los Angeles, California, United States
Wien Center
🇺🇸Miami Beach, Florida, United States
University of Kentucky, Lexington, Sanders-Brown Center on Aging/Neurology
🇺🇸Lexington, Kentucky, United States
Saint Louis University, Department of Psychiatry
🇺🇸St. Louis, Missouri, United States
Dent Neurological Institute
🇺🇸Amherst, New York, United States
Mayo Clinic, Jacksonville
🇺🇸Jacksonville, Florida, United States
Mayo Clinic Rochester, Alzheimer's Disease Research Center
🇺🇸Rochester, Minnesota, United States
University of Alabama, Birmingham
🇺🇸Birmingham, Alabama, United States
UC-Davis Alzheimer's Disease Center
🇺🇸Sacramento, California, United States
Pacific Research Network
🇺🇸San Diego, California, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
University of South Florida Suncoast Alzheimer's and Gerontology Center
🇺🇸Tampa, Florida, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Boston University Alzheimer's Disease Clinical and Research Program
🇺🇸Boston, Massachusetts, United States
University of Michigan Dept. of Neurology
🇺🇸Ann Arbor, Michigan, United States
Wake Forest University Health Services
🇺🇸Winston-Salem, North Carolina, United States
Case Western Reserve University Memory and Aging Center
🇺🇸Cleveland, Ohio, United States
Baylor University Department of Neurology
🇺🇸Houston, Texas, United States
Oregon Health and Science University Neurology
🇺🇸Portland, Oregon, United States
Meharry Medical College
🇺🇸Nashville, Tennessee, United States
University of Washington/Seattle Institute for Biomedical & Clinical Research
🇺🇸Seattle, Washington, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States