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

Alzheimer's Disease Clinical Trial

— DHA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00440050
• Other study ID #: IA0099
• Secondary ID: 1RC2AG036535ADC-
• Status: Completed
• Phase: Phase 3
• First received: February 22, 2007
• Last updated: September 15, 2014
• Start date: February 2007
• Est. completion date: May 2009

Study information

• Verified date: September 2014
• Source: Alzheimer's Disease Cooperative Study (ADCS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 402
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• DHA (Docosahexaenoic Acid)
950 mg soft-gel capsules which contain approximately 510 mg DHA, 2 capsules twice a day for 18 months
• Placebo
2 placebo capsules twice a day for 18 months

Locations

Country	Name	City	State
United States	Albany Medical College	Albany	New York
United States	Dent Neurological Institute	Amherst	New York
United States	University of Michigan Dept. of Neurology	Ann Arbor	Michigan
United States	Emory University Dept. of Psychiatry	Atlanta	Georgia
United States	Johns Hopkins University Division of Cognitive Neuroscience	Baltimore	Maryland
United States	The Memory Clinic	Bennington	Vermont
United States	University of Alabama, Birmingham	Birmingham	Alabama
United States	Boston University Alzheimer's Disease Clinical and Research Program	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Mount Sinai School of Medicine	Bronx	New York
United States	Northwestern University Cognitive Neurology and Alzheimer Disease Center	Chicago	Illinois
United States	Rush Alzheimer's Disease Center	Chicago	Illinois
United States	Case Western Reserve University Memory and Aging Center	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	University of Texas Southwestern-Memory Research Unit	Dallas	Texas
United States	Saint Mary's Health Care	Grand Rapids	Michigan
United States	Baylor University Department of Neurology	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of California Irvine	Irvine	California
United States	Mayo Clinic, Jacksonville	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	UCSD Shiley-Marcos Alzheimer's Research Center	La Jolla	California
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky, Lexington, Sanders-Brown Center on Aging/Neurology	Lexington	Kentucky
United States	UCLA Neurology	Los Angeles	California
United States	University of Southern California Psychiatry and Behavioral Sciences	Los Angeles	California
United States	University of Wisconsin Department of Medicine	Madison	Wisconsin
United States	Wien Center	Miami Beach	Florida
United States	Meharry Medical College	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	New York University Medical Center	New York	New York
United States	Medical University of South Carolina	North Charleston	South Carolina
United States	Palo Alto Institute for Research & Education	Palo Alto	California
United States	Banner Alzheimer's Institute	Phoenix	Arizona
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University Neurology	Portland	Oregon
United States	Rhode Island Hospital Neurology	Providence	Rhode Island
United States	Mayo Clinic Rochester, Alzheimer's Disease Research Center	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	UC-Davis Alzheimer's Disease Center	Sacramento	California
United States	Pacific Research Network	San Diego	California
United States	University of Washington/Seattle Institute for Biomedical & Clinical Research	Seattle	Washington
United States	Saint Louis University, Department of Psychiatry	St. Louis	Missouri
United States	Washington University ADRC-Memory and Aging Project	St. Louis	Missouri
United States	Sun Health Research Institute/Arizona Consortium	Sun City	Arizona
United States	Byrd Alzheimer's Institute	Tampa	Florida
United States	University of South Florida Suncoast Alzheimer's and Gerontology Center	Tampa	Florida
United States	Georgetown University Medical Center, Dept. of Neurology	Washington	District of Columbia
United States	Howard University College of Medicine	Washington	District of Columbia
United States	Wake Forest University Health Services	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Alzheimer's Disease Cooperative Study (ADCS)	DSM Nutritional Products, Inc., National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

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. Review. — View Citation

Kalmijn S, van Boxtel MP, Ocké 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No