Age-Related Eye Disease Study 2 (AREDS2)

Cataract Clinical Trial

— AREDS2  

Official title:

Age-Related Eye Disease Study 2 (AREDS2): A Multi-center, Randomized Trial of Lutein, Zeaxanthin and Omega-3 Long-Chain Polyunsaturated Fatty Acids (Docosahexaenoic Acid [DHA] and Eicosapentaenoic Acid [EPA]) in Age-Related Macular Degeneration

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00345176
• Other study ID #: NEI-120
• Secondary ID: N01-EY-5-0007HHS
• Status: Completed
• Phase: Phase 3
• First received: June 14, 2006
• Last updated: April 13, 2015
• Start date: September 2006
• Est. completion date: October 2012

Study information

• Verified date: April 2015
• Source: National Eye Institute (NEI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00409513

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4203
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 85 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Age-related Macular Degeneration
• Cataract
• Eye Diseases
• Macular Degeneration

Intervention

Dietary Supplement:
• Lutein/zeaxanthin
10 mg lutein and 2 mg zeaxanthin (1 tablet) Placebo-DHA/EPA (2 soft-gel capsules)
• DHA/EPA
Placebo-lutein/zeaxanthin (1 tablet) 350 mg DHA and 650 mg EPA (2 soft-gel capsules)

Drug:
• 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)

Locations

Country	Name	City	State
United States	Texas Retina Associates	Arlington	Texas
United States	Western Carolina Retinal Associates	Asheville	North Carolina
United States	Emory University Eye Center	Atlanta	Georgia
United States	Elman Retina Group	Baltimore	Maryland
United States	Wilmer Eye Institute, Johns Hopkins Hospital	Baltimore	Maryland
United States	National Eye Institute	Bethesda	Maryland
United States	Retina-Vitreous Associates Medical Group	Beverly Hills	California
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	Fletcher Allen Health Care	Burlington	Vermont
United States	Pennsylvania Retina Specialists, PC	Camp Hill	Pennsylvania
United States	UNC Department of Ophthalmology	Chapel Hill	North Carolina
United States	Charlotte Eye Ear Nose and Throat Associates	Charlotte	North Carolina
United States	The Retina Group of Washington	Chevy Chase	Maryland
United States	Northwestern University	Chicago	Illinois
United States	The University of Illinois	Chicago	Illinois
United States	Case Western Reserve University	Cleveland	Ohio
United States	Retina Associates of Cleveland	Cleveland	Ohio
United States	Carolina Retina Center	Columbia	South Carolina
United States	Palmetto Retina Center	Columbia	South Carolina
United States	University Health Care - Mason Eye Institute	Columbia	Missouri
United States	Ohio State University	Columbus	Ohio
United States	Texas Retina Associates	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Georgia Retina, PC	Decatur	Georgia
United States	Colorado Retina Associates	Denver	Colorado
United States	Henry Ford Health System - Eye Care Services	Detroit	Michigan
United States	Kresge Eye Institute	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	The Retina Group of Washington	Fairfax	Virginia
United States	Retina Group of Florida	Ft. Lauderdale	Florida
United States	NorthShore University HealthSystems	Glenview	Illinois
United States	Vision Research Foundation	Grand Rapids	Michigan
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Penn State M.S. Hershey Medical Center	Hershey	Pennsylvania
United States	Baylor College of Medicine	Houston	Texas
United States	Retina Consultants of Houston	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	University of Florida	Jacksonville	Florida
United States	Eye Foundation of Kansas City	Kansas City	Missouri
United States	Mid-America Retina Consultants, PA	Kansas City	Missouri
United States	Southeastern Retina Associates, PC	Knoxville	Tennessee
United States	Shiley Eye Center - UCSD	La Jolla	California
United States	Delaware Valley Retina Associates	Lawrenceville	New Jersey
United States	Retina Associates of Kentucky	Lexington	Kentucky
United States	Jones Eye Institute - UAMS	Little Rock	Arkansas
United States	Loma Linda University	Loma Linda	California
United States	Doheny Eye Institute	Los Angeles	California
United States	Jules Stein Eye Institute	Los Angeles	California
United States	Eldorado Retina Associates, PC	Louisville	Colorado
United States	Texas Retina Associates	Lubbock	Texas
United States	Ophthalmic Consultants of Long Island	Lynbrook	New York
United States	University of Wisconsin	Madison	Wisconsin
United States	VA Northern California Health Care System	Martinez	California
United States	University of Tennessee	Memphis	Tennessee
United States	Bascom Palmer Eye Institute	Miami	Florida
United States	Retina Associates of Cleveland	Middleburg Heights	Ohio
United States	The Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt Eye Institute	Nashville	Tennessee
United States	Yale University Eye Center	New Haven	Connecticut
United States	Manhattan Eye, Ear and Throat Hospital	New York	New York
United States	New York Eye and Ear Infirmary	New York	New York
United States	UMDNJ	Newark	New Jersey
United States	Dean McGee Eye Institute	Oklahoma City	Oklahoma
United States	Paducah Retinal Center	Paducah	Kentucky
United States	Southern California Desert Retina Consultants, MC	Palm Springs	California
United States	Scheie Eye Institute	Philadelphia	Pennsylvania
United States	Wills Eye Hospital/Mid Atlantic Retina	Philadelphia	Pennsylvania
United States	Retina Vitreous Consultants	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Devers Eye Institute	Portland	Oregon
United States	Retina Northwest, PC	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester Eye Institute	Rochester	New York
United States	Vision Research Foundation	Royal Oak	Michigan
United States	University of California, Davis	Sacramento	California
United States	John Moran Eye Center	Salt Lake City	Utah
United States	Pacific Eye Associates	San Francisco	California
United States	West Coast Retina Medical Group, Inc	San Francisco	California
United States	Sarasota Retina Institute	Sarasota	Florida
United States	Retina Center Northwest	Silverdale	Washington
United States	Retina Consultants, PLLC	Slingerlands	New York
United States	The Retina Institute	St Louis	Missouri
United States	Washington University School of Medicine	St. Louis	Missouri
United States	The Research Foundation of SUNY/Stony Brook	Stony Brook	New York
United States	Scott and White Memorial Hospital	Temple	Texas
United States	Vision Research Foundation	Traverse City	Michigan
United States	Wake Forest University Eye Center	Winston-Salem	North Carolina
United States	Center for Retina and Macular Disease	Winter Haven	Florida
United States	Retina Associates of Cleveland	Youngstown	Ohio

Sponsors (4)

Lead Sponsor	Collaborator
National Eye Institute (NEI)	National Center for Complementary and Integrative Health (NCCIH), National Heart, Lung, and Blood Institute (NHLBI), Office of Dietary Supplements (ODS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incident Cardiovascular Disease	Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on cardiovascular disease	5 years of follow-up	No
Other	Cognition as Measured by a Telephone Battery	Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin, zinc, and beta-carotene on cognitive function	5 years of follow-up	No
Other	Prevalence of Peripheral Changes as Measured Using OPTOS Imaging	Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on the peripheral retina	5 years of follow-up	No
Other	Genetics for the Association of AMD and Cataract		5 years of follow-up	No
Other	Genetics for the Progression of AMD and Cataract		5 years of follow-up	No
Primary	Development of Advanced AMD in People at Moderate to High Risk for Progression.	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.	5 years of follow-up	No
Secondary	Progression to Moderate Vision Loss	Loss defined as >/= 3 lines of letters from baseline or treatment for choroidal neovascularization	5 years of follow-up	No
Secondary	Adverse Events	Safety outcomes included serious adverse events and mortality.	5 years of follow-up	Yes
Secondary	Progression to Cataract Surgery	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.	5 years of follow-up	No

External Links

•   AREDS2 Website
•   NEI Website: Age-Related Eye Disease Study 2