Age-Related Eye Disease Study 2 (AREDS2)

Sponsor
National Eye Institute (NEI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00345176
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH), Office of Dietary Supplements (ODS) (NIH), National Center for Complementary and Integrative Health (NCCIH) (NIH)
4,203
91
4
73
46.2
0.6

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Dietary Supplement: Lutein/zeaxanthin
  • Dietary Supplement: DHA/EPA
  • Drug: Lutein/zeaxanthin and DHA/EPA
Phase 3

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

  2. Outcome is measured with a battery of tests administered over the telephone at baseline, and at years 2 and 4 of the study.

  3. Primary outcome is the change in the composite score for the results of the cognitive function testing from baseline over time.

  4. Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on cardiovascular disease

  1. Primary measure of cardiovascular morbidity and mortality
  1. Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on the peripheral retina
  1. Primary outcome is the development of peripheral drusen, geographic atrophy, reticular pigmentary changes, and pseudoreticular drusen.
  1. Association of genotype polymorphisms with age-related macular degeneration and cataract
  1. Whole genome sequencing will be completed. Evaluation of association genetic associations with disease will be conducted using AREDS controls.
  1. Association of genotype polymorphisms with progression of age-related macular degeneration
  1. 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.
  1. 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.

  2. 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
4203 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Study Start Date :
Sep 1, 2006
Actual Primary Completion Date :
Oct 1, 2012
Actual Study Completion Date :
Oct 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Lutein/Zeaxanthin

lutein (10mg)/zeaxanthin (2 mg)

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

Active Comparator: DHA/EPA

DHA (350 mg)/EPA (650 mg)

Dietary Supplement: DHA/EPA
Placebo-lutein/zeaxanthin (1 tablet) 350 mg DHA and 650 mg EPA (2 soft-gel capsules)
Other Names:
  • docosahexaenoic acid; eicosapentaenoic acid
  • Active Comparator: Lutein/Zeaxanthin + DHA/EPA

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

    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)

    Placebo Comparator: Placebo/Control

    Considered control because all participants received the AREDS formulation

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. Progression to Moderate Vision Loss [5 years of follow-up]

      Loss defined as >/= 3 lines of letters from baseline or treatment for choroidal neovascularization

    2. Adverse Events [5 years of follow-up]

      Safety outcomes included serious adverse events and mortality.

    3. 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.

    Other Outcome Measures

    1. Incident Cardiovascular Disease [5 years of follow-up]

      Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on cardiovascular disease

    2. Cognition as Measured by a Telephone Battery [5 years of follow-up]

      Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin, zinc, and beta-carotene on cognitive function

    3. Prevalence of Peripheral Changes as Measured Using OPTOS Imaging [5 years of follow-up]

      Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on the peripheral retina

    4. Genetics for the Association of AMD and Cataract [5 years of follow-up]

    5. Genetics for the Progression of AMD and Cataract [5 years of follow-up]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35294
    2 Jones Eye Institute - UAMS Little Rock Arkansas United States 72205
    3 Retina-Vitreous Associates Medical Group Beverly Hills California United States 90211
    4 Shiley Eye Center - UCSD La Jolla California United States 92093
    5 Loma Linda University Loma Linda California United States 92354
    6 Doheny Eye Institute Los Angeles California United States 90033
    7 Jules Stein Eye Institute Los Angeles California United States 90095
    8 VA Northern California Health Care System Martinez California United States 94553
    9 Southern California Desert Retina Consultants, MC Palm Springs California United States 92262
    10 University of California, Davis Sacramento California United States 95817
    11 West Coast Retina Medical Group, Inc San Francisco California United States 94107
    12 Pacific Eye Associates San Francisco California United States 94115
    13 Colorado Retina Associates Denver Colorado United States 80218
    14 Eldorado Retina Associates, PC Louisville Colorado United States 80027
    15 Yale University Eye Center New Haven Connecticut United States 06510
    16 Retina Group of Florida Ft. Lauderdale Florida United States 33334
    17 University of Florida Jacksonville Florida United States 32209
    18 Bascom Palmer Eye Institute Miami Florida United States 33136
    19 Sarasota Retina Institute Sarasota Florida United States 34239
    20 Center for Retina and Macular Disease Winter Haven Florida United States 33880
    21 Emory University Eye Center Atlanta Georgia United States 30322
    22 Georgia Retina, PC Decatur Georgia United States 30030
    23 Northwestern University Chicago Illinois United States 60611
    24 The University of Illinois Chicago Illinois United States 60612
    25 NorthShore University HealthSystems Glenview Illinois United States 60026
    26 Ingalls Memorial Hospital Harvey Illinois United States 60426
    27 University of Iowa Iowa City Iowa United States 52242
    28 Retina Associates of Kentucky Lexington Kentucky United States 40509
    29 Paducah Retinal Center Paducah Kentucky United States 42001
    30 Elman Retina Group Baltimore Maryland United States 21237
    31 Wilmer Eye Institute, Johns Hopkins Hospital Baltimore Maryland United States 21287
    32 National Eye Institute Bethesda Maryland United States 20892
    33 The Retina Group of Washington Chevy Chase Maryland United States 20815
    34 Massachusetts Eye and Ear Infirmary Boston Massachusetts United States 02114
    35 Ophthalmic Consultants of Boston Boston Massachusetts United States 02114
    36 Kresge Eye Institute Detroit Michigan United States 48201
    37 Henry Ford Health System - Eye Care Services Detroit Michigan United States 48202
    38 Vision Research Foundation Grand Rapids Michigan United States 49546
    39 Vision Research Foundation Royal Oak Michigan United States 48073
    40 Vision Research Foundation Traverse City Michigan United States 49686
    41 Mayo Clinic Rochester Minnesota United States 55905
    42 University Health Care - Mason Eye Institute Columbia Missouri United States 65212
    43 Eye Foundation of Kansas City Kansas City Missouri United States 64108
    44 Mid-America Retina Consultants, PA Kansas City Missouri United States 64111
    45 The Retina Institute St Louis Missouri United States 63110
    46 Washington University School of Medicine St. Louis Missouri United States 63110
    47 Delaware Valley Retina Associates Lawrenceville New Jersey United States 08648
    48 UMDNJ Newark New Jersey United States 07103
    49 Ophthalmic Consultants of Long Island Lynbrook New York United States 11563
    50 New York Eye and Ear Infirmary New York New York United States 10003
    51 Manhattan Eye, Ear and Throat Hospital New York New York United States 10021
    52 University of Rochester Eye Institute Rochester New York United States 14642
    53 Retina Consultants, PLLC Slingerlands New York United States 12159
    54 The Research Foundation of SUNY/Stony Brook Stony Brook New York United States 11794
    55 Western Carolina Retinal Associates Asheville North Carolina United States 28803
    56 UNC Department of Ophthalmology Chapel Hill North Carolina United States 27599
    57 Charlotte Eye Ear Nose and Throat Associates Charlotte North Carolina United States 28210
    58 Duke University Durham North Carolina United States 27710
    59 Wake Forest University Eye Center Winston-Salem North Carolina United States 27157
    60 Case Western Reserve University Cleveland Ohio United States 44106
    61 Retina Associates of Cleveland Cleveland Ohio United States 44122
    62 Ohio State University Columbus Ohio United States 43210
    63 Retina Associates of Cleveland Middleburg Heights Ohio United States 44130
    64 Retina Associates of Cleveland Youngstown Ohio United States 44505
    65 Dean McGee Eye Institute Oklahoma City Oklahoma United States 73104
    66 Devers Eye Institute Portland Oregon United States 97210
    67 Retina Northwest, PC Portland Oregon United States 97210
    68 Pennsylvania Retina Specialists, PC Camp Hill Pennsylvania United States 17011
    69 Penn State M.S. Hershey Medical Center Hershey Pennsylvania United States 17033
    70 Scheie Eye Institute Philadelphia Pennsylvania United States 19104
    71 Wills Eye Hospital/Mid Atlantic Retina Philadelphia Pennsylvania United States 19107
    72 Retina Vitreous Consultants Pittsburgh Pennsylvania United States 15213
    73 University of Pittsburgh Medical Center Pittsburgh Pennsylvania United States 15213
    74 Palmetto Retina Center Columbia South Carolina United States 29204
    75 Carolina Retina Center Columbia South Carolina United States 29223
    76 Southeastern Retina Associates, PC Knoxville Tennessee United States 37909
    77 University of Tennessee Memphis Tennessee United States 38163
    78 Vanderbilt Eye Institute Nashville Tennessee United States 37232
    79 Texas Retina Associates Arlington Texas United States 76012
    80 Texas Retina Associates Dallas Texas United States 75231
    81 UT Southwestern Medical Center Dallas Texas United States 75390
    82 Baylor College of Medicine Houston Texas United States 77030
    83 Retina Consultants of Houston Houston Texas United States 77030
    84 Texas Retina Associates Lubbock Texas United States 79424
    85 Scott and White Memorial Hospital Temple Texas United States 76508
    86 John Moran Eye Center Salt Lake City Utah United States 84132
    87 Fletcher Allen Health Care Burlington Vermont United States 05401
    88 The Retina Group of Washington Fairfax Virginia United States 22031
    89 Retina Center Northwest Silverdale Washington United States 98383
    90 University of Wisconsin Madison Wisconsin United States 53705
    91 The Medical College of Wisconsin Milwaukee Wisconsin United States 53226

    Sponsors and Collaborators

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

    Investigators

    • Study Chair: Emily Y Chew, MD, National Eye Institute, National Institutes of Health
    • Study Director: John Paul SanGiovanni, Sc.D., National Eye Institute, National Institutes of Health

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    National Eye Institute (NEI)
    ClinicalTrials.gov Identifier:
    NCT00345176
    Other Study ID Numbers:
    • NEI-120
    • N01-EY-5-0007
    • HHS-N-260-2005-00007-C
    • CC-070025
    • 07-EI-0025
    • NCT00409513
    First Posted:
    Jun 27, 2006
    Last Update Posted:
    May 5, 2015
    Last Verified:
    Apr 1, 2015
    Keywords provided by National Eye Institute (NEI)
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Between October 2006 and September 2008 a total of 4,203 participants aged 50 - 85 years were randomized at 82 clinical sites.
    Pre-assignment Detail Prior to randomization, participants had to complete the Qualification phase. They could only be randomized if they took at least 75% of the run-in medication.
    Arm/Group Title Placebo/Control Lutein/Zeaxanthin DHA/EPA Lutein/Zeaxanthin + DHA/EPA
    Arm/Group Description Considered control because all participants received the AREDS formulation lutein (10mg)/zeaxanthin (2 mg) DHA (350 mg)/EPA (650 mg) lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
    Period Title: Overall Study
    STARTED 1012 1044 1068 1079
    COMPLETED 1007 1038 1062 1069
    NOT COMPLETED 5 6 6 10

    Baseline Characteristics

    Arm/Group Title Placebo/Control Lutein/Zeaxanthin DHA/EPA Lutein/Zeaxanthin + DHA/EPA Total
    Arm/Group Description Considered control because all participants received the AREDS formulation lutein (10mg)/zeaxanthin (2 mg) DHA (350 mg)/EPA (650 mg) lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg) Total of all reporting groups
    Overall Participants 1012 1044 1068 1079 4203
    Age (Median) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [Participants]
    74
    7.3%
    74
    7.1%
    74
    6.9%
    75
    7%
    74
    1.8%
    Sex: Female, Male (Count of Participants)
    Female
    548
    54.2%
    596
    57.1%
    603
    56.5%
    641
    59.4%
    2388
    56.8%
    Male
    464
    45.8%
    448
    42.9%
    465
    43.5%
    438
    40.6%
    1815
    43.2%

    Outcome Measures

    1. Primary Outcome
    Title Development of Advanced AMD in People at Moderate to High Risk for Progression.
    Description 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.
    Time Frame 5 years of follow-up

    Outcome Measure Data

    Analysis Population Description
    Intention to Treat. Participants lost to follow-up during the course of the study were censored at the time of last contact.
    Arm/Group Title Placebo/Control Lutein/Zeaxanthin DHA/EPA Lutein/Zeaxanthin + DHA/EPA
    Arm/Group Description Considered control because all participants received the AREDS formulation lutein (10mg)/zeaxanthin (2 mg) DHA (350 mg)/EPA (650 mg) lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
    Measure Participants 1007 1038 1062 1069
    Measure Eyes 1691 1709 1749 1742
    Number [Eyes]
    493
    468
    507
    472
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo/Control, Lutein/Zeaxanthin
    Comments Each of the 3 active arms was compared to the placebo/control arm.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.013
    Comments Adjusted for 3 treatment versus placebo comparisons and interim analyses
    Method Regression, Cox
    Comments Adjusted for baseline AMD status
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.90
    Confidence Interval (2-Sided) 98.7%
    0.76 to 1.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments The reference group is placebo.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo/Control, DHA/EPA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.013
    Comments Adjusted for multiple comparisons
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.97
    Confidence Interval (2-Sided) 98.7%
    0.82 to 1.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo/Control, Lutein/Zeaxanthin + DHA/EPA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.013
    Comments
    Method Regression, Cox
    Comments Adjusted for multiple comparisons
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.89
    Confidence Interval (2-Sided) 98.7%
    0.75 to 1.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Progression to Moderate Vision Loss
    Description Loss defined as >/= 3 lines of letters from baseline or treatment for choroidal neovascularization
    Time Frame 5 years of follow-up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo/Control Lutein/Zeaxanthin DHA/EPA Lutein/Zeaxanthin + DHA/EPA
    Arm/Group Description Considered control because all participants received the AREDS formulation lutein (10mg)/zeaxanthin (2 mg) DHA (350 mg)/EPA (650 mg) lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
    Measure Participants 1007 1038 1062 1069
    Measure Eyes 1630 1660 1694 1672
    Number [Eyes]
    515
    509
    519
    506
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo/Control, Lutein/Zeaxanthin
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.05
    Comments
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.95
    Confidence Interval (2-Sided) 95%
    0.84 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo/Control, DHA/EPA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.05
    Comments
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.96
    Confidence Interval (2-Sided) 95%
    0.84 to 1.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo/Control, Lutein/Zeaxanthin + DHA/EPA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.05
    Comments
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.94
    Confidence Interval (2-Sided) 95%
    0.83 to 1.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Adverse Events
    Description Safety outcomes included serious adverse events and mortality.
    Time Frame 5 years of follow-up

    Outcome Measure Data

    Analysis Population Description
    Number of deaths in 5 years
    Arm/Group Title Placebo/Control Lutein/Zeaxanthin DHA/EPA Lutein/Zeaxanthin + DHA/EPA
    Arm/Group Description Considered control because all participants received the AREDS formulation lutein (10mg)/zeaxanthin (2 mg) DHA (350 mg)/EPA (650 mg) lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
    Measure Participants 1012 1044 1068 1079
    Mortality
    81
    8%
    87
    8.3%
    96
    9%
    104
    9.6%
    Serious Adverse Events
    479
    47.3%
    484
    46.4%
    505
    47.3%
    519
    48.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo/Control, Lutein/Zeaxanthin
    Comments Comparison of Lutein/Zeaxantin versus Control for mortality
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.05
    Comments
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.04
    Confidence Interval (2-Sided) 95%
    0.77 to 1.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo/Control, DHA/EPA
    Comments Comparison of DHA/EPA versus Placebo for mortality
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.05
    Comments
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.13
    Confidence Interval (2-Sided) 95%
    0.84 to 1.52
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo/Control, Lutein/Zeaxanthin + DHA/EPA
    Comments Comparison of Lutein/Zeaxanthin + DHA/EPA versus Placebo for Mortality
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.05
    Comments
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.23
    Confidence Interval (2-Sided) 95%
    0.92 to 1.65
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Progression to Cataract Surgery
    Description 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.
    Time Frame 5 years of follow-up

    Outcome Measure Data

    Analysis Population Description
    Includes participants who were phakic in at least 1 eye at baseline
    Arm/Group Title No Lutein/Zeaxanthin Lutein/Zeaxanthin
    Arm/Group Description Lutein main effect - includes participants who did not receive Lutein/Zeaxanthin Lutein main effect - includes all participants who received Lutein/Zeaxanthin
    Measure Participants 1577 1578
    Measure Eyes 3022 3005
    Number [Eyes]
    708
    681
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo/Control, Lutein/Zeaxanthin
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.05
    Comments
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.96
    Confidence Interval (2-Sided) 95%
    0.84 to 1.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Other Pre-specified Outcome
    Title Incident Cardiovascular Disease
    Description Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on cardiovascular disease
    Time Frame 5 years of follow-up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    6. Other Pre-specified Outcome
    Title Cognition as Measured by a Telephone Battery
    Description Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin, zinc, and beta-carotene on cognitive function
    Time Frame 5 years of follow-up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    7. Other Pre-specified Outcome
    Title Prevalence of Peripheral Changes as Measured Using OPTOS Imaging
    Description Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on the peripheral retina
    Time Frame 5 years of follow-up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    8. Other Pre-specified Outcome
    Title Genetics for the Association of AMD and Cataract
    Description
    Time Frame 5 years of follow-up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    9. Other Pre-specified Outcome
    Title Genetics for the Progression of AMD and Cataract
    Description
    Time Frame 5 years of follow-up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame 5 years
    Adverse Event Reporting Description Adverse events reported by System Organ Class
    Arm/Group Title Placebo/Control Lutein/Zeaxanthin DHA/EPA Lutein/Zeaxanthin + DHA/EPA
    Arm/Group Description Considered control because all participants received the AREDS formulation lutein (10mg)/zeaxanthin (2 mg) DHA (350 mg)/EPA (650 mg) lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
    All Cause Mortality
    Placebo/Control Lutein/Zeaxanthin DHA/EPA Lutein/Zeaxanthin + DHA/EPA
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo/Control Lutein/Zeaxanthin DHA/EPA Lutein/Zeaxanthin + DHA/EPA
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 479/1012 (47.3%) 484/1044 (46.4%) 505/1068 (47.3%) 519/1079 (48.1%)
    Blood and lymphatic system disorders
    Blood and lymphatic system disorders 12/1012 (1.2%) 14 11/1044 (1.1%) 11 9/1068 (0.8%) 10 7/1079 (0.6%) 7
    Cardiac disorders
    Cardiac Disorders 96/1012 (9.5%) 122 110/1044 (10.5%) 138 119/1068 (11.1%) 144 103/1079 (9.5%) 133
    Congenital, familial and genetic disorders
    Congenital, familian and genetic disorders 3/1012 (0.3%) 3 1/1044 (0.1%) 1 0/1068 (0%) 0 0/1079 (0%) 0
    Ear and labyrinth disorders
    Ear and labyrinth disorders 7/1012 (0.7%) 7 3/1044 (0.3%) 3 4/1068 (0.4%) 4 1/1079 (0.1%) 1
    Endocrine disorders
    Endocrine disorders 2/1012 (0.2%) 2 3/1044 (0.3%) 3 3/1068 (0.3%) 3 0/1079 (0%) 0
    Eye disorders
    Eye disorders 3/1012 (0.3%) 3 11/1044 (1.1%) 13 4/1068 (0.4%) 6 0/1079 (0%) 0
    Gastrointestinal disorders
    Gastrointestinal disorders 76/1012 (7.5%) 101 69/1044 (6.6%) 81 58/1068 (5.4%) 72 61/1079 (5.7%) 71
    General disorders
    General disorders and administration site conditions 54/1012 (5.3%) 60 50/1044 (4.8%) 54 51/1068 (4.8%) 58 46/1079 (4.3%) 50
    Hepatobiliary disorders
    Hepatobiliary disorders 8/1012 (0.8%) 8 16/1044 (1.5%) 16 16/1068 (1.5%) 16 17/1079 (1.6%) 18
    Immune system disorders
    Immune system disorders 2/1012 (0.2%) 2 1/1044 (0.1%) 1 2/1068 (0.2%) 2 2/1079 (0.2%) 2
    Infections and infestations
    Infections and infestations 90/1012 (8.9%) 109 102/1044 (9.8%) 139 103/1068 (9.6%) 144 99/1079 (9.2%) 127
    Injury, poisoning and procedural complications
    Injury, poisoning and procedural complications 76/1012 (7.5%) 90 62/1044 (5.9%) 72 74/1068 (6.9%) 90 66/1079 (6.1%) 84
    Investigations
    Investigations 14/1012 (1.4%) 14 19/1044 (1.8%) 20 13/1068 (1.2%) 15 12/1079 (1.1%) 12
    Metabolism and nutrition disorders
    Metabolism and nutrition disorders 21/1012 (2.1%) 22 16/1044 (1.5%) 18 13/1068 (1.2%) 13 23/1079 (2.1%) 25
    Musculoskeletal and connective tissue disorders
    Musculoskeletal and connective tissue disorders 66/1012 (6.5%) 77 74/1044 (7.1%) 91 71/1068 (6.6%) 85 85/1079 (7.9%) 101
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) 80/1012 (7.9%) 103 88/1044 (8.4%) 111 83/1068 (7.8%) 100 92/1079 (8.5%) 112
    Nervous system disorders
    Nervous system disorders 66/1012 (6.5%) 73 74/1044 (7.1%) 93 72/1068 (6.7%) 87 73/1079 (6.8%) 86
    Psychiatric disorders
    Psychiatric disorders 4/1012 (0.4%) 4 5/1044 (0.5%) 5 5/1068 (0.5%) 5 9/1079 (0.8%) 11
    Renal and urinary disorders
    Renal and urinary disorders 19/1012 (1.9%) 20 25/1044 (2.4%) 26 24/1068 (2.2%) 25 25/1079 (2.3%) 29
    Reproductive system and breast disorders
    Reproductive system and breast disorders 9/1012 (0.9%) 11 8/1044 (0.8%) 8 12/1068 (1.1%) 13 11/1079 (1%) 11
    Respiratory, thoracic and mediastinal disorders
    Respioratory, thoracic and mediastinal disorders 44/1012 (4.3%) 59 43/1044 (4.1%) 52 37/1068 (3.5%) 50 46/1079 (4.3%) 51
    Skin and subcutaneous tissue disorders
    Skin and subcutaneous tissue disorders 1/1012 (0.1%) 1 6/1044 (0.6%) 7 3/1068 (0.3%) 3 5/1079 (0.5%) 5
    Surgical and medical procedures
    Surgical and medical procedures 32/1012 (3.2%) 32 29/1044 (2.8%) 31 27/1068 (2.5%) 30 32/1079 (3%) 32
    Vascular disorders
    Vascular disorders 41/1012 (4.1%) 45 40/1044 (3.8%) 42 42/1068 (3.9%) 45 42/1079 (3.9%) 46
    Other (Not Including Serious) Adverse Events
    Placebo/Control Lutein/Zeaxanthin DHA/EPA Lutein/Zeaxanthin + DHA/EPA
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 717/1012 (70.8%) 791/1044 (75.8%) 759/1068 (71.1%) 791/1079 (73.3%)
    Eye disorders
    Dry eye 55/1012 (5.4%) 62 39/1044 (3.7%) 40 64/1068 (6%) 70 62/1079 (5.7%) 70
    Eye disorder 67/1012 (6.6%) 100 67/1044 (6.4%) 96 62/1068 (5.8%) 98 82/1079 (7.6%) 152
    Visual disturbance 88/1012 (8.7%) 118 110/1044 (10.5%) 139 84/1068 (7.9%) 116 88/1079 (8.2%) 119
    Vitreous disorder 133/1012 (13.1%) 208 154/1044 (14.8%) 213 165/1068 (15.4%) 228 162/1079 (15%) 208
    Gastrointestinal disorders
    Change in bowel habit 57/1012 (5.6%) 69 67/1044 (6.4%) 77 48/1068 (4.5%) 58 57/1079 (5.3%) 60
    Infections and infestations
    Bronchitis 62/1012 (6.1%) 72 69/1044 (6.6%) 83 57/1068 (5.3%) 80 56/1079 (5.2%) 66
    Upper respiratory tract infection 139/1012 (13.7%) 175 150/1044 (14.4%) 190 139/1068 (13%) 179 138/1079 (12.8%) 173
    Urinary tract infection 57/1012 (5.6%) 82 75/1044 (7.2%) 103 71/1068 (6.6%) 108 73/1079 (6.8%) 96
    Vascular disorders
    Hypertension 59/1012 (5.8%) 66 60/1044 (5.7%) 62 69/1068 (6.5%) 72 73/1079 (6.8%) 73

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Traci Clemons, PhD
    Organization The EMMES Corporation
    Phone 301-251-1161 ext 212
    Email tclemons@emmes.com
    Responsible Party:
    National Eye Institute (NEI)
    ClinicalTrials.gov Identifier:
    NCT00345176
    Other Study ID Numbers:
    • NEI-120
    • N01-EY-5-0007
    • HHS-N-260-2005-00007-C
    • CC-070025
    • 07-EI-0025
    • NCT00409513
    First Posted:
    Jun 27, 2006
    Last Update Posted:
    May 5, 2015
    Last Verified:
    Apr 1, 2015