DHA (Docosahexaenoic Acid), an Omega 3 Fatty Acid, in Slowing the Progression of Alzheimer's Disease (DHA)

A Randomized Double-Blind Placebo-Controlled Trial Of The Effects Of Docosahexaenoic Acid (DHA) In Slowing The Progression Of Alzheimer's Disease

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).

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: DHA (Docosahexaenoic Acid); Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 402
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama, Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer's Institute
    • Sun City, Arizona, United States, 85351
      • Sun Health Research Institute/Arizona Consortium
  • California
    • Irvine, California, United States, 92697
      • University of California Irvine
    • La Jolla, California, United States, 92037
      • UCSD Shiley-Marcos Alzheimer's Research Center
    • Los Angeles, California, United States, 90095
      • UCLA Neurology
    • Los Angeles, California, United States, 90033
      • University of Southern California Psychiatry and Behavioral Sciences
    • Palo Alto, California, United States, 94304
      • Palo Alto Institute for Research & Education
    • Sacramento, California, United States, 95817
      • UC-Davis Alzheimer's Disease Center
    • San Diego, California, United States, 92103
      • Pacific Research Network
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School Of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Georgetown University Medical Center, Dept. of Neurology
    • Washington, District of Columbia, United States, 20060
      • Howard University College of Medicine
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic, Jacksonville
    • Miami Beach, Florida, United States, 33140
      • Wien Center
    • Tampa, Florida, United States, 33617
      • University of South Florida Suncoast Alzheimer's and Gerontology Center
    • Tampa, Florida, United States, 33647
      • Byrd Alzheimer's Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Dept. of Psychiatry
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush Alzheimer's Disease Center
    • Chicago, Illinois, United States, 60611
      • Northwestern University Cognitive Neurology and Alzheimer Disease Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky, Lexington, Sanders-Brown Center on Aging/Neurology
  • Maryland
    • Baltimore, Maryland, United States, 20205
      • Johns Hopkins University Division of Cognitive Neuroscience
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02118
      • Boston University Alzheimer's Disease Clinical and Research Program
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan Dept. of Neurology
    • Grand Rapids, Michigan, United States, 49503
      • Saint Mary's Health Care
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester, Alzheimer's Disease Research Center
  • Missouri
    • St. Louis, Missouri, United States, 63104
      • Saint Louis University, Department of Psychiatry
    • St. Louis, Missouri, United States, 63108
      • Washington University ADRC-Memory and Aging Project
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • Amherst, New York, United States, 14226
      • Dent Neurological Institute
    • Bronx, New York, United States, 10468
      • Mount Sinai School of Medicine
    • New York, New York, United States, 10016
      • New York University Medical Center
    • New York, New York, United States, 10032
      • Columbia University
    • Rochester, New York, United States, 14620
      • University of Rochester Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Services
  • Ohio
    • Cleveland, Ohio, United States, 44120
      • Case Western Reserve University Memory and Aging Center
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University Neurology
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital Neurology
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37208
      • Meharry Medical College
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern-Memory Research Unit
    • Houston, Texas, United States, 77030
      • Baylor University Department of Neurology
  • Vermont
    • Bennington, Vermont, United States, 05201
      • The Memory Clinic
  • Washington
    • Seattle, Washington, United States, 98108
      • University of Washington/Seattle Institute for Biomedical & Clinical Research
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin Department of Medicine

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
• 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2.; Placebo	Drug: Placebo; 2 placebo capsules twice a day for 18 months
Experimental: 1.; DHA	Drug: DHA (Docosahexaenoic Acid); 950 mg soft-gel capsules which contain approximately 510 mg DHA, 2 capsules twice a day for 18 months; Other Names: Neuromins

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Change on the ADAS-Cog 11.	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.	Baseline, 6, 12, 18 months
Rate of Change on CDR-SOB	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.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ADCS-ADL	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.	18 months
Neuropsychiatric Inventory (NPI)	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.	18 months

Collaborators and Investigators

• Sponsor: Alzheimer's Disease Cooperative Study (ADCS)
• Collaborators: National Institute on Aging (NIA); DSM Nutritional Products, Inc.
• Investigators: Principal Investigator: Joseph Quinn, MD, Oregon Health and Science University

Publications and helpful links

General Publications

• Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Wilson RS, Aggarwal N, Schneider J. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol. 2003 Jul;60(7):940-6. doi: 10.1001/archneur.60.7.940.
• Horrocks LA, Farooqui AA. Docosahexaenoic acid in the diet: its importance in maintenance and restoration of neural membrane function. Prostaglandins Leukot Essent Fatty Acids. 2004 Apr;70(4):361-72. doi: 10.1016/j.plefa.2003.12.011.
• Kalmijn S, van Boxtel MP, Ocke M, Verschuren WM, Kromhout D, Launer LJ. Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology. 2004 Jan 27;62(2):275-80. doi: 10.1212/01.wnl.0000103860.75218.a5.
• Suzuki H, Morikawa Y, Takahashi H. Effect of DHA oil supplementation on intelligence and visual acuity in the elderly. World Rev Nutr Diet. 2001;88:68-71. doi: 10.1159/000059767. No abstract available.
• Calon F, Lim GP, Yang F, Morihara T, Teter B, Ubeda O, Rostaing P, Triller A, Salem N Jr, Ashe KH, Frautschy SA, Cole GM. Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model. Neuron. 2004 Sep 2;43(5):633-45. doi: 10.1016/j.neuron.2004.08.013.
• Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, Salem N Jr, Frautschy SA, Cole GM. A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci. 2005 Mar 23;25(12):3032-40. doi: 10.1523/JNEUROSCI.4225-04.2005.
• Yassine HN, Rawat V, Mack WJ, Quinn JF, Yurko-Mauro K, Bailey-Hall E, Aisen PS, Chui HC, Schneider LS. The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer's disease. Alzheimers Res Ther. 2016 Jun 30;8:25. doi: 10.1186/s13195-016-0194-x.
• Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, Galvin JE, Emond J, Jack CR Jr, Weiner M, Shinto L, Aisen PS. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA. 2010 Nov 3;304(17):1903-11. doi: 10.1001/jama.2010.1510.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: February 22, 2007
• First Submitted That Met QC Criteria: February 22, 2007
• First Posted (Estimate): February 26, 2007

Study Record Updates

• Last Update Posted (Estimate): September 25, 2014
• Last Update Submitted That Met QC Criteria: September 15, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: omega-3 fatty acids; EPA; fish oil
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: IA0099; 1RC2AG036535 (U.S. NIH Grant/Contract); ADC-027-DHA