Age-Related Eye Disease Study 2 (AREDS2)
- Conditions
- CataractAge-related Macular Degeneration
- Interventions
- Dietary Supplement: Lutein/zeaxanthinDietary Supplement: DHA/EPADrug: Lutein/zeaxanthin and DHA/EPA
- Registration Number
- NCT00345176
- Lead Sponsor
- National Eye Institute (NEI)
- Brief Summary
Oral supplementation with the Age-Related Eye Disease Study (AREDS) formulation (antioxidant vitamins C and E, beta carotene, and zinc) has been shown to reduce the risk of progression to advanced age-related macular degeneration (AMD). Observational data suggest that increased dietary intake of lutein + zeaxanthin (carotenoids), omega-3 long-chain polyunsaturated fatty acids (docosahexaenoic acid \[DHA\] + eicosapentaenoic acid \[EPA\]), or both might further reduce this risk. AREDS2 was designed to test whether adding lutein + zeaxanthin, DHA + EPA, or lutein + zeaxanthin and DHA + EPA to the AREDS formulation might further reduce the risk of progression to advanced AMD. A secondary goal was to test the effects of eliminating beta carotene and reducing zinc dose in the AREDS formulation.
- Detailed Description
AREDS2 was a randomized, double-masked, placebo-controlled, 2x2 factorial trial evaluating the risks and benefits of adding lutein (10 mg) + zeaxanthin (2 mg), DHA (350 mg) + EPA (650 mg), or both to the AREDS formulation, which consisted of vitamins C (500 mg), vitamin E (400 international units), beta carotene (15 mg), zinc (80 mg as zinc oxide), and copper (2 mg as cupric oxide) for the treatment of progression to advanced AMD. The study enrolled 4,203 participants aged 50 to 85 years, with sufficiently clear ocular media to allow accurate assessment of AMD from fundus photographs. Subjects were enrolled on the basis of the AREDS Simplified Severity Scale for defining risk categories for development of advanced age-related macular degeneration. All participants were offered additional treatment with the original AREDS formulation (now considered standard of care) and 3 variations of this formula. These are: (1) no beta-carotene; (2) lower amount of zinc (25 mg); and (3) no beta-carotene and lower amount of zinc (25 mg). Eligible participants were followed for a minimum of five years.
Multiple ancillary studies were conducted using the parent study (AREDS2) data to explore:
1. Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin, zinc, and beta-carotene on cognitive function
1. Outcome is measured with a battery of tests administered over the telephone at baseline, and at years 2 and 4 of the study.
2. Primary outcome is the change in the composite score for the results of the cognitive function testing from baseline over time.
2. Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on cardiovascular disease
a. Primary measure of cardiovascular morbidity and mortality
3. Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on the peripheral retina
a. Primary outcome is the development of peripheral drusen, geographic atrophy, reticular pigmentary changes, and pseudoreticular drusen.
4. Association of genotype polymorphisms with age-related macular degeneration and cataract
a. Whole genome sequencing will be completed. Evaluation of association genetic associations with disease will be conducted using AREDS controls.
5. Association of genotype polymorphisms with progression of age-related macular degeneration
a. Whole genome sequencing is conducted. Progression from early to late and severe stages of AMD will be examined with the genotype data to evaluate the risks of progression associated with the genotype polymorphisms.
6. Association of genotype polymorphisms with dietary intake a. Whole genome sequencing is conducted. Progression from early to late and severe stages of AMD will be examined regarding potential interaction of the dietary intake with the genotype data to evaluate the risks of progression.
7. Association of genotype polymorphisms with AREDS2 supplements a. Interaction of genetic polymorphisms with AREDS2 supplements for progression to late AMD will be evaluated using the data from the whole genome sequencing project.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 4203
- Men and women between the ages of 50 and 85 years
- Macular status ranges from large drusen in both eyes or large drusen in one eye and advanced AMD (neovascular AMD or geographic atrophy) in the fellow eye
- Ocular media not clear enough to allow good fundus photography
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lutein/Zeaxanthin Lutein/zeaxanthin lutein (10mg)/zeaxanthin (2 mg) DHA/EPA DHA/EPA DHA (350 mg)/EPA (650 mg) Lutein/Zeaxanthin + DHA/EPA Lutein/zeaxanthin and DHA/EPA lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
- Primary Outcome Measures
Name Time Method Development of Advanced AMD in People at Moderate to High Risk for Progression. 5 years of follow-up Defined as central geographic atrophy or retinal features of choroidal neovascularization detected on central grading of the stereoscopic fundus photographs or a history of treatment for advanced AMD after study enrollment.
- Secondary Outcome Measures
Name Time Method Adverse Events 5 years of follow-up Safety outcomes included serious adverse events and mortality.
Progression to Cataract Surgery 5 years of follow-up The study examined the effects of lutein/zeaxanthin on progression to cataract surgery with data collected during regular telephone contacts and the annual study visits.
Progression to Moderate Vision Loss 5 years of follow-up Loss defined as \>/= 3 lines of letters from baseline or treatment for choroidal neovascularization
Trial Locations
- Locations (84)
Retina Associates of Cleveland
🇺🇸Youngstown, Ohio, United States
Massachusetts Eye and Ear Infirmary
🇺🇸Boston, Massachusetts, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Southern California Desert Retina Consultants, MC
🇺🇸Palm Springs, California, United States
Center for Retina and Macular Disease
🇺🇸Winter Haven, Florida, United States
VA Northern California Health Care System
🇺🇸Martinez, California, United States
Ophthalmic Consultants of Boston
🇺🇸Boston, Massachusetts, United States
University of Rochester Eye Institute
🇺🇸Rochester, New York, United States
Retina-Vitreous Associates Medical Group
🇺🇸Beverly Hills, California, United States
University Health Care - Mason Eye Institute
🇺🇸Columbia, Missouri, United States
UMDNJ
🇺🇸Newark, New Jersey, United States
Jules Stein Eye Institute
🇺🇸Los Angeles, California, United States
Loma Linda University
🇺🇸Loma Linda, California, United States
Manhattan Eye, Ear and Throat Hospital
🇺🇸New York, New York, United States
Retina Group of Florida
🇺🇸Ft. Lauderdale, Florida, United States
Georgia Retina, PC
🇺🇸Decatur, Georgia, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Eldorado Retina Associates, PC
🇺🇸Louisville, Colorado, United States
Emory University Eye Center
🇺🇸Atlanta, Georgia, United States
The University of Illinois
🇺🇸Chicago, Illinois, United States
Retina Consultants, PLLC
🇺🇸Slingerlands, New York, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
NorthShore University HealthSystems
🇺🇸Glenview, Illinois, United States
The Retina Institute
🇺🇸St Louis, Missouri, United States
Ingalls Memorial Hospital
🇺🇸Harvey, Illinois, United States
Ophthalmic Consultants of Long Island
🇺🇸Lynbrook, New York, United States
The Research Foundation of SUNY/Stony Brook
🇺🇸Stony Brook, New York, United States
Texas Retina Associates
🇺🇸Lubbock, Texas, United States
Retina Center Northwest
🇺🇸Silverdale, Washington, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Retina Consultants of Houston
🇺🇸Houston, Texas, United States
Bascom Palmer Eye Institute
🇺🇸Miami, Florida, United States
Duke University
🇺🇸Durham, North Carolina, United States
West Coast Retina Medical Group, Inc
🇺🇸San Francisco, California, United States
Pacific Eye Associates
🇺🇸San Francisco, California, United States
Vanderbilt Eye Institute
🇺🇸Nashville, Tennessee, United States
John Moran Eye Center
🇺🇸Salt Lake City, Utah, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Colorado Retina Associates
🇺🇸Denver, Colorado, United States
Kresge Eye Institute
🇺🇸Detroit, Michigan, United States
Dean McGee Eye Institute
🇺🇸Oklahoma City, Oklahoma, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Henry Ford Health System - Eye Care Services
🇺🇸Detroit, Michigan, United States
Devers Eye Institute
🇺🇸Portland, Oregon, United States
Retina Northwest, PC
🇺🇸Portland, Oregon, United States
The Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
National Eye Institute
🇺🇸Bethesda, Maryland, United States
Paducah Retinal Center
🇺🇸Paducah, Kentucky, United States
Retina Associates of Kentucky
🇺🇸Lexington, Kentucky, United States
The Retina Group of Washington
🇺🇸Fairfax, Virginia, United States
Western Carolina Retinal Associates
🇺🇸Asheville, North Carolina, United States
Pennsylvania Retina Specialists, PC
🇺🇸Camp Hill, Pennsylvania, United States
Scheie Eye Institute
🇺🇸Philadelphia, Pennsylvania, United States
Penn State M.S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Palmetto Retina Center
🇺🇸Columbia, South Carolina, United States
Retina Vitreous Consultants
🇺🇸Pittsburgh, Pennsylvania, United States
Sarasota Retina Institute
🇺🇸Sarasota, Florida, United States
University of Florida
🇺🇸Jacksonville, Florida, United States
Vision Research Foundation
🇺🇸Traverse City, Michigan, United States
Washington University School of Medicine
🇺🇸St. Louis, Missouri, United States
New York Eye and Ear Infirmary
🇺🇸New York, New York, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Shiley Eye Center - UCSD
🇺🇸La Jolla, California, United States
Doheny Eye Institute
🇺🇸Los Angeles, California, United States
Charlotte Eye Ear Nose and Throat Associates
🇺🇸Charlotte, North Carolina, United States
Scott and White Memorial Hospital
🇺🇸Temple, Texas, United States
Wills Eye Hospital/Mid Atlantic Retina
🇺🇸Philadelphia, Pennsylvania, United States
Fletcher Allen Health Care
🇺🇸Burlington, Vermont, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Wake Forest University Eye Center
🇺🇸Winston-Salem, North Carolina, United States
Eye Foundation of Kansas City
🇺🇸Kansas City, Missouri, United States
UNC Department of Ophthalmology
🇺🇸Chapel Hill, North Carolina, United States
Mid-America Retina Consultants, PA
🇺🇸Kansas City, Missouri, United States
Yale University Eye Center
🇺🇸New Haven, Connecticut, United States
University of California, Davis
🇺🇸Sacramento, California, United States
Jones Eye Institute - UAMS
🇺🇸Little Rock, Arkansas, United States
Elman Retina Group
🇺🇸Baltimore, Maryland, United States
Wilmer Eye Institute, Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Delaware Valley Retina Associates
🇺🇸Lawrenceville, New Jersey, United States
Carolina Retina Center
🇺🇸Columbia, South Carolina, United States
Southeastern Retina Associates, PC
🇺🇸Knoxville, Tennessee, United States
University of Tennessee
🇺🇸Memphis, Tennessee, United States