Age-Related Eye Disease Study 2 (AREDS2)

NCT ID: NCT00345176

Last Updated: 2015-05-05

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

4203 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-09-30

Study Completion Date

2012-10-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Age-related Macular Degeneration Cataract

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Lutein/Zeaxanthin

lutein (10mg)/zeaxanthin (2 mg)

Group Type ACTIVE_COMPARATOR

Lutein/zeaxanthin

Intervention Type DIETARY_SUPPLEMENT

10 mg lutein and 2 mg zeaxanthin (1 tablet) Placebo-DHA/EPA (2 soft-gel capsules)

DHA/EPA

DHA (350 mg)/EPA (650 mg)

Group Type ACTIVE_COMPARATOR

DHA/EPA

Intervention Type DIETARY_SUPPLEMENT

Placebo-lutein/zeaxanthin (1 tablet) 350 mg DHA and 650 mg EPA (2 soft-gel capsules)

Lutein/Zeaxanthin + DHA/EPA

lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)

Group Type ACTIVE_COMPARATOR

Lutein/zeaxanthin and DHA/EPA

Intervention Type DRUG

10 mg lutein and 2 mg zeaxanthin (1 tablet) 350 mg DHA and 650 mg EPA (2 soft-gel capsules)

Placebo/Control

Considered control because all participants received the AREDS formulation

Group Type PLACEBO_COMPARATOR

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Lutein/zeaxanthin

10 mg lutein and 2 mg zeaxanthin (1 tablet) Placebo-DHA/EPA (2 soft-gel capsules)

Intervention Type DIETARY_SUPPLEMENT

DHA/EPA

Placebo-lutein/zeaxanthin (1 tablet) 350 mg DHA and 650 mg EPA (2 soft-gel capsules)

Intervention Type DIETARY_SUPPLEMENT

Lutein/zeaxanthin and DHA/EPA

10 mg lutein and 2 mg zeaxanthin (1 tablet) 350 mg DHA and 650 mg EPA (2 soft-gel capsules)

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

docosahexaenoic acid; eicosapentaenoic acid

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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

Exclusion Criteria

* Ocular media not clear enough to allow good fundus photography
Minimum Eligible Age

50 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Office of Dietary Supplements (ODS)

NIH

Sponsor Role collaborator

National Center for Complementary and Integrative Health (NCCIH)

NIH

Sponsor Role collaborator

National Eye Institute (NEI)

NIH

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Emily Y Chew, MD

Role: STUDY_CHAIR

National Eye Institute, National Institutes of Health

John Paul SanGiovanni, Sc.D.

Role: STUDY_DIRECTOR

National Eye Institute, National Institutes of Health

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Jones Eye Institute - UAMS

Little Rock, Arkansas, United States

Site Status

Retina-Vitreous Associates Medical Group

Beverly Hills, California, United States

Site Status

Shiley Eye Center - UCSD

La Jolla, California, United States

Site Status

Loma Linda University

Loma Linda, California, United States

Site Status

Doheny Eye Institute

Los Angeles, California, United States

Site Status

Jules Stein Eye Institute

Los Angeles, California, United States

Site Status

VA Northern California Health Care System

Martinez, California, United States

Site Status

Southern California Desert Retina Consultants, MC

Palm Springs, California, United States

Site Status

University of California, Davis

Sacramento, California, United States

Site Status

West Coast Retina Medical Group, Inc

San Francisco, California, United States

Site Status

Pacific Eye Associates

San Francisco, California, United States

Site Status

Colorado Retina Associates

Denver, Colorado, United States

Site Status

Eldorado Retina Associates, PC

Louisville, Colorado, United States

Site Status

Yale University Eye Center

New Haven, Connecticut, United States

Site Status

Retina Group of Florida

Fort Lauderdale, Florida, United States

Site Status

University of Florida

Jacksonville, Florida, United States

Site Status

Bascom Palmer Eye Institute

Miami, Florida, United States

Site Status

Sarasota Retina Institute

Sarasota, Florida, United States

Site Status

Center for Retina and Macular Disease

Winter Haven, Florida, United States

Site Status

Emory University Eye Center

Atlanta, Georgia, United States

Site Status

Georgia Retina, PC

Decatur, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

The University of Illinois

Chicago, Illinois, United States

Site Status

NorthShore University HealthSystems

Glenview, Illinois, United States

Site Status

Ingalls Memorial Hospital

Harvey, Illinois, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

Retina Associates of Kentucky

Lexington, Kentucky, United States

Site Status

Paducah Retinal Center

Paducah, Kentucky, United States

Site Status

Elman Retina Group

Baltimore, Maryland, United States

Site Status

Wilmer Eye Institute, Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

National Eye Institute

Bethesda, Maryland, United States

Site Status

The Retina Group of Washington

Chevy Chase, Maryland, United States

Site Status

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, United States

Site Status

Ophthalmic Consultants of Boston

Boston, Massachusetts, United States

Site Status

Kresge Eye Institute

Detroit, Michigan, United States

Site Status

Henry Ford Health System - Eye Care Services

Detroit, Michigan, United States

Site Status

Vision Research Foundation

Grand Rapids, Michigan, United States

Site Status

Vision Research Foundation

Royal Oak, Michigan, United States

Site Status

Vision Research Foundation

Traverse City, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

University Health Care - Mason Eye Institute

Columbia, Missouri, United States

Site Status

Eye Foundation of Kansas City

Kansas City, Missouri, United States

Site Status

Mid-America Retina Consultants, PA

Kansas City, Missouri, United States

Site Status

The Retina Institute

St Louis, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Delaware Valley Retina Associates

Lawrenceville, New Jersey, United States

Site Status

UMDNJ

Newark, New Jersey, United States

Site Status

Ophthalmic Consultants of Long Island

Lynbrook, New York, United States

Site Status

New York Eye and Ear Infirmary

New York, New York, United States

Site Status

Manhattan Eye, Ear and Throat Hospital

New York, New York, United States

Site Status

University of Rochester Eye Institute

Rochester, New York, United States

Site Status

Retina Consultants, PLLC

Slingerlands, New York, United States

Site Status

The Research Foundation of SUNY/Stony Brook

Stony Brook, New York, United States

Site Status

Western Carolina Retinal Associates

Asheville, North Carolina, United States

Site Status

UNC Department of Ophthalmology

Chapel Hill, North Carolina, United States

Site Status

Charlotte Eye Ear Nose and Throat Associates

Charlotte, North Carolina, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Wake Forest University Eye Center

Winston-Salem, North Carolina, United States

Site Status

Case Western Reserve University

Cleveland, Ohio, United States

Site Status

Retina Associates of Cleveland

Cleveland, Ohio, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

Retina Associates of Cleveland

Middleburg Heights, Ohio, United States

Site Status

Retina Associates of Cleveland

Youngstown, Ohio, United States

Site Status

Dean McGee Eye Institute

Oklahoma City, Oklahoma, United States

Site Status

Devers Eye Institute

Portland, Oregon, United States

Site Status

Retina Northwest, PC

Portland, Oregon, United States

Site Status

Pennsylvania Retina Specialists, PC

Camp Hill, Pennsylvania, United States

Site Status

Penn State M.S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Scheie Eye Institute

Philadelphia, Pennsylvania, United States

Site Status

Wills Eye Hospital/Mid Atlantic Retina

Philadelphia, Pennsylvania, United States

Site Status

Retina Vitreous Consultants

Pittsburgh, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Palmetto Retina Center

Columbia, South Carolina, United States

Site Status

Carolina Retina Center

Columbia, South Carolina, United States

Site Status

Southeastern Retina Associates, PC

Knoxville, Tennessee, United States

Site Status

University of Tennessee

Memphis, Tennessee, United States

Site Status

Vanderbilt Eye Institute

Nashville, Tennessee, United States

Site Status

Texas Retina Associates

Arlington, Texas, United States

Site Status

Texas Retina Associates

Dallas, Texas, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Retina Consultants of Houston

Houston, Texas, United States

Site Status

Texas Retina Associates

Lubbock, Texas, United States

Site Status

Scott and White Memorial Hospital

Temple, Texas, United States

Site Status

John Moran Eye Center

Salt Lake City, Utah, United States

Site Status

Fletcher Allen Health Care

Burlington, Vermont, United States

Site Status

The Retina Group of Washington

Fairfax, Virginia, United States

Site Status

Retina Center Northwest

Silverdale, Washington, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

The Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev. 2023 Sep 13;9(9):CD000254. doi: 10.1002/14651858.CD000254.pub5.

Reference Type DERIVED
PMID: 37702300 (View on PubMed)

Bhandari S, Vitale S, Agron E, Clemons TE, Chew EY; Age-Related Eye Disease Study 2 Research Group. Cataract Surgery and the Risk of Developing Late Age-Related Macular Degeneration: The Age-Related Eye Disease Study 2 Report Number 27. Ophthalmology. 2022 Apr;129(4):414-420. doi: 10.1016/j.ophtha.2021.11.014. Epub 2021 Nov 16.

Reference Type DERIVED
PMID: 34793832 (View on PubMed)

Keenan TD, Agron E, Mares JA, Clemons TE, van Asten F, Swaroop A, Chew EY; AREDS and AREDS2 Research Groups. Adherence to a Mediterranean diet and cognitive function in the Age-Related Eye Disease Studies 1 & 2. Alzheimers Dement. 2020 Jun;16(6):831-842. doi: 10.1002/alz.12077. Epub 2020 Apr 13.

Reference Type DERIVED
PMID: 32285590 (View on PubMed)

Chew EY, Clemons TE, Agron E, Launer LJ, Grodstein F, Bernstein PS; Age-Related Eye Disease Study 2 (AREDS2) Research Group. Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial. JAMA. 2015 Aug 25;314(8):791-801. doi: 10.1001/jama.2015.9677.

Reference Type DERIVED
PMID: 26305649 (View on PubMed)

Writing Group for the AREDS2 Research Group; Bonds DE, Harrington M, Worrall BB, Bertoni AG, Eaton CB, Hsia J, Robinson J, Clemons TE, Fine LJ, Chew EY. Effect of long-chain omega-3 fatty acids and lutein + zeaxanthin supplements on cardiovascular outcomes: results of the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA Intern Med. 2014 May;174(5):763-71. doi: 10.1001/jamainternmed.2014.328.

Reference Type DERIVED
PMID: 24638908 (View on PubMed)

Age-Related Eye Disease Study 2 (AREDS2) Research Group; Chew EY, Clemons TE, Sangiovanni JP, Danis RP, Ferris FL 3rd, Elman MJ, Antoszyk AN, Ruby AJ, Orth D, Bressler SB, Fish GE, Hubbard GB, Klein ML, Chandra SR, Blodi BA, Domalpally A, Friberg T, Wong WT, Rosenfeld PJ, Agron E, Toth CA, Bernstein PS, Sperduto RD. Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3. JAMA Ophthalmol. 2014 Feb;132(2):142-9. doi: 10.1001/jamaophthalmol.2013.7376.

Reference Type DERIVED
PMID: 24310343 (View on PubMed)

Domalpally A, Danis RP, Chew EY, Clemons TE, Reed S, Sangiovanni JP, Ferris FL 3rd; Age-Related Eye Disease Study 2 Research Group. Evaluation of optimized digital fundus reflex photographs for lens opacities in the age-related eye disease study 2: AREDS2 report 7. Invest Ophthalmol Vis Sci. 2013 Sep 5;54(9):5989-94. doi: 10.1167/iovs.13-12301.

Reference Type DERIVED
PMID: 23887802 (View on PubMed)

Toy BC, Krishnadev N, Indaram M, Cunningham D, Cukras CA, Chew EY, Wong WT. Drusen regression is associated with local changes in fundus autofluorescence in intermediate age-related macular degeneration. Am J Ophthalmol. 2013 Sep;156(3):532-542.e1. doi: 10.1016/j.ajo.2013.04.031. Epub 2013 Jul 3.

Reference Type DERIVED
PMID: 23830564 (View on PubMed)

Age-Related Eye Disease Study 2 (AREDS2) Research Group; Chew EY, SanGiovanni JP, Ferris FL, Wong WT, Agron E, Clemons TE, Sperduto R, Danis R, Chandra SR, Blodi BA, Domalpally A, Elman MJ, Antoszyk AN, Ruby AJ, Orth D, Bressler SB, Fish GE, Hubbard GB, Klein ML, Friberg TR, Rosenfeld PJ, Toth CA, Bernstein P. Lutein/zeaxanthin for the treatment of age-related cataract: AREDS2 randomized trial report no. 4. JAMA Ophthalmol. 2013 Jul;131(7):843-50. doi: 10.1001/jamaophthalmol.2013.4412.

Reference Type DERIVED
PMID: 23645227 (View on PubMed)

Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA. 2013 May 15;309(19):2005-15. doi: 10.1001/jama.2013.4997.

Reference Type DERIVED
PMID: 23644932 (View on PubMed)

Danis RP, Domalpally A, Chew EY, Clemons TE, Armstrong J, SanGiovanni JP, Ferris FL 3rd; AREDS2 Study Group. Methods and reproducibility of grading optimized digital color fundus photographs in the Age-Related Eye Disease Study 2 (AREDS2 Report Number 2). Invest Ophthalmol Vis Sci. 2013 Jul 8;54(7):4548-54. doi: 10.1167/iovs.13-11804.

Reference Type DERIVED
PMID: 23620429 (View on PubMed)

Bernstein PS, Ahmed F, Liu A, Allman S, Sheng X, Sharifzadeh M, Ermakov I, Gellermann W. Macular pigment imaging in AREDS2 participants: an ancillary study of AREDS2 subjects enrolled at the Moran Eye Center. Invest Ophthalmol Vis Sci. 2012 Sep 14;53(10):6178-86. doi: 10.1167/iovs.12-10275.

Reference Type DERIVED
PMID: 22879423 (View on PubMed)

Hubbard LD, Danis RP, Neider MW, Thayer DW, Wabers HD, White JK, Pugliese AJ, Pugliese MF; Age-Related Eye Disease 2 Research Group. Brightness, contrast, and color balance of digital versus film retinal images in the age-related eye disease study 2. Invest Ophthalmol Vis Sci. 2008 Aug;49(8):3269-82. doi: 10.1167/iovs.07-1267. Epub 2008 Apr 17.

Reference Type DERIVED
PMID: 18421079 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

http://www.nei.nih.gov/areds2/

NEI Website: Age-Related Eye Disease Study 2

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

N01-EY-5-0007

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

HHS-N-260-2005-00007-C

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

CC-070025

Identifier Type: OTHER

Identifier Source: secondary_id

07-EI-0025

Identifier Type: OTHER

Identifier Source: secondary_id

NEI-120

Identifier Type: -

Identifier Source: org_study_id

NCT00409513

Identifier Type: -

Identifier Source: nct_alias

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Age-Related Eye Disease Study (AREDS) Follow-Up
NCT00594672 ACTIVE_NOT_RECRUITING