Clinical trial NCT00440050: DHA (Docosahexaenoic Acid), an Omega 3 Fatty Acid, in Slowing the Progression of Alzheimer's Disease
Official title: A Randomized Double-Blind Placebo-Controlled Trial Of The Effects Of Docosahexaenoic Acid (DHA) In Slowing The Progression Of Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer's Disease
Keywords: fish oil
omega-3 fatty acids
EPA
Lead sponsor: Alzheimer's Disease Cooperative Study (ADCS)
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: DSM Nutritional Products, Inc.
First posted: 2007-02-26
Enrollment: 402
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Rate of Change on the ADAS-Cog 11.
timeFrame: Baseline, 6, 12, 18 months
measure: Rate of Change on CDR-SOB
timeFrame: 18 months
Secondary outcomes:
measure: ADCS-ADL
timeFrame: 18 months
measure: Neuropsychiatric Inventory (NPI)
timeFrame: 18 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Banner Alzheimer's Institute
state: Arizona
city: Sun City
country: United States
facility: Sun Health Research Institute/Arizona Consortium
state: Arizona
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: La Jolla
country: United States
facility: UCSD Shiley-Marcos Alzheimer's Research Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California Psychiatry and Behavioral Sciences
state: California
city: Los Angeles
country: United States
facility: UCLA Neurology
state: California
city: Palo Alto
country: United States
facility: Palo Alto Institute for Research & Education
state: California
city: Sacramento
country: United States
facility: UC-Davis Alzheimer's Disease Center
state: California
city: San Diego
country: United States
facility: Pacific Research Network
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center, Dept. of Neurology
state: District of Columbia
city: Washington
country: United States
facility: Howard University College of Medicine
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic, Jacksonville
state: Florida
city: Miami Beach
country: United States
facility: Wien Center
state: Florida
city: Tampa
country: United States
facility: University of South Florida Suncoast Alzheimer's and Gerontology Center
state: Florida
city: Tampa
country: United States
facility: Byrd Alzheimer's Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Dept. of Psychiatry
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Cognitive Neurology and Alzheimer Disease Center
state: Illinois
city: Chicago
country: United States
facility: Rush Alzheimer's Disease Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky, Lexington, Sanders-Brown Center on Aging/Neurology
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University Division of Cognitive Neuroscience
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University Alzheimer's Disease Clinical and Research Program
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Dept. of Neurology
state: Michigan
city: Grand Rapids
country: United States
facility: Saint Mary's Health Care
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester, Alzheimer's Disease Research Center
state: Minnesota
city: St. Louis
country: United States
facility: Saint Louis University, Department of Psychiatry
state: Missouri
city: St. Louis
country: United States
facility: Washington University ADRC-Memory and Aging Project
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Amherst
country: United States
facility: Dent Neurological Institute
state: New York
city: Bronx
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Services
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University Memory and Aging Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University Neurology
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital Neurology
state: Rhode Island
city: North Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Meharry Medical College
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern-Memory Research Unit
state: Texas
city: Houston
country: United States
facility: Baylor University Department of Neurology
state: Texas
city: Bennington
country: United States
facility: The Memory Clinic
state: Vermont
city: Seattle
country: United States
facility: University of Washington/Seattle Institute for Biomedical & Clinical Research
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Department of Medicine
state: Wisconsin
Study officials:
affiliation: Oregon Health and Science University
name: Joseph Quinn, MD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1016/j.plefa.2003.12.011.
citation: 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.
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. doi: 10.1001/archneur.60.7.940.
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. doi: 10.1159/000059767. No abstract available.
citation: 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.
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. doi: 10.1523/JNEUROSCI.4225-04.2005.
citation: 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.
citation: 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.