Clinical trial NCT00345176
Conditions: Age-related Macular Degeneration Cataract
Keywords: age-related macular degeneration AMD lutein zeaxanthin docosahexaenoic acid eicosapentaenoic acid
Sponsor: National Eye Institute (NEI)
Start date: 2006-09-01; Completion date: 2012-10-01
Enrollment: 4203 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: lutein (10mg)/zeaxanthin (2 mg) arm 2: DHA (350 mg)/EPA (650 mg) arm 3: lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg) arm 4: Considered control because all participants received the AREDS formulation
Interventions: intervention 1: Lutein/zeaxanthin intervention 2: DHA/EPA intervention 3: Lutein/zeaxanthin and DHA/EPA
Intervention descriptions: intervention 1: 10 mg lutein and 2 mg zeaxanthin (1 tablet) Placebo-DHA/EPA (2 soft-gel capsules) intervention 2: Placebo-lutein/zeaxanthin (1 tablet) 350 mg DHA and 650 mg EPA (2 soft-gel capsules) intervention 3: 10 mg lutein and 2 mg zeaxanthin (1 tablet) 350 mg DHA and 650 mg EPA (2 soft-gel capsules)

Protocol documents: