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The 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
This study is NOT currently recruiting participants.
Summary | Eligibility | Citations | Contacts
Summary
Number |
07-EI-0025 |
Sponsoring Institute |
National Eye Institute (NEI) |
Recruitment Detail |
Type: No longer recruiting/follow-up only |
Referral Letter Required |
No |
Population Exclusion(s) |
Children |
Special Instructions |
Currently Not Provided |
Keywords |
Age Related Macular Degeneration; |
Recruitment Keyword(s) |
Age-Related Macular Degeneration; |
Condition(s) |
Age-Related Macular Degeneration (AMD); |
Investigational Drug(s) |
Lutein, Zeaxanthin, DHA, EPA, Vit C, Vit E, Beta-carotene, zinc oxide, cupric ox |
Investigational Device(s) |
None |
Intervention(s) |
Drug: Lutein, zeaxanthin, DHA, EPA |
Supporting Site |
|
Patients ages 50 to 85 who are at high risk of having advanced age-related macular degeneration may be eligible for this study. About 4,000 people will participate for 5 years. At the first clinic visit, patients will have an eye examination, have their eyes photographed, and learn about the study. They will receive a supply of placebos (sugar pills) and the standard formulation of the Age-Related Eye Disease Study supplement, which has vitamin C, vitamin E, beta-carotene, zinc oxide, and cupric oxide (copper). Patients who have smoked within the past year will not receive the standard formulation, for there is an increased risk of lung cancer for people taking beta-carotene. The second visit, 1 to 3 months later, involves an eye examination, vision check, and blood sample taken if patients agree to enter a substudy of other nutrient formulations.
This study uses omega-3 long-chain polyunsaturated fatty acids (fish oils): docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Patients are placed randomly into four groups: receiving a placebo; lutein and zeaxanthin only; fatty acids only; and lutein and zeaxanthin plus fatty acids. During study visits and phone calls, patients will be asked about possible side effects. After 1 year, they will have an eye examination and photographs of the eyes, and will be asked about side effects from the pills they have been taking. There will be annual follow-ups for the study's 5 year duration.
Risks include those involved in any routine eye examination such as discomfort or allergic reaction to eye drops used during eye examinations and drops for dilating the eyes that can cause a sudden increase in pressure in very few individuals. The supplements taken can also involve some symptoms. Fatty acids can cause mild gastrointestinal problems. Vitamin E side effects are rare but include fatigue and muscle weakness. In people without enough vitamin K, high doses of vitamin E may slow down clotting of blood. High doses of zinc can sometimes causes stomach upset.
This study may have direct benefits for participants. They can learn more about their own eyes and eye disease. Knowledge gained can also help other people at risk for developing eye diseases in the future.
Eligibility
INCLUSION CRITERIA:
Children are not included because AMD is, by definition, an adult disease.
- Men and women aged 50 to 85 years at the Qualification Visit.
- Bilateral large drusen (greater than or equal to 125 microns) or large drusen in one eye and advanced AMD in the fellow eye. A study eye (eye without advanced AMD) may have definite geographic atrophy not involving the center of the macula without evidence of drusen.
- Study eye(s) with fundus photographs assessed by the Reading Center to be of adequate photo quality.
- Pupillary dilation greater than or equal to 5 mm in each eye for all participants, except that dilation less than 5 mm in an aphakic or pseudophakic eye will not exclude a participant with adequate quality fundus photographs.
- Randomization within three months following the Qualification Visit.
- Willingness to stop taking any supplements containing lutein, zeaxanthin, omega-3 LCPUFAs (specifically DHA and EPA), vitamin C, vitamin E, beta-carotene, zinc or copper, other than those supplied by AREDS2. Willingness to stop taking other supplements is demonstrated by refraining from use of vitamin or mineral supplements that are part of the randomized trial during the entire run-in period. Continued use of nutritional supplements that are not part of the randomized trial (e.g., calcium) does not exclude a participant, provided that these supplements are taken one to two hours before or after the study supplements. If the participant wants to continue taking a multivitamin and/or multimineral supplement during the study he/she will be provided Centrum Silver.
- Demonstration that at least 75 percent of run-in medication was consumed, as determined by an estimated count of the remaining run-in tablets/capsules (exceptions may be made by appeal to the AREDS2 Coordinating Center) and willingness to take the randomized trial supplements for the next five years.
- Likelihood, willingness, and ability to undergo examinations at yearly intervals for at least five years.
- People who currently smoke are eligible to enroll in this study. However, if the smoker elects to participate in the AREDS-type supplement (ATS) formulation randomization, they will be randomized to one of the two arms of the AREDS formulation without beta-carotene.
- Ability and willingness to consent to both the Qualification and the
Randomization/Follow up phases of the study. Participants will be
provided a Participant Information Booklet (Appendix III) that will explain the overall study. For clinical sites using two consent forms, the First Informed Consent describes the responsibilities of the participant and the study during the run-in period. The Second Informed Consent describes responsibilities following randomization. For clinical sites using the AREDS2 Central IRB or whose local IRB requests it, the information in the First and Second Informed Consent has been combined into one document that must be signed at the Qualification Visit. Model informed consent forms are provided in Appendix B. For sites using two consent forms, an AREDS2 Second Informed Consent must be signed even if a First Informed Consent was signed previously.
- Participants with advanced AMD in one eye may have received treatment for advanced AMD in the eye identified as having advanced AMD. These treatments include: intravitreal injections of pharmacological agents (i.e. Avastin(Registered Trademark), Lucentis(Trademark), Macugen(Registered Trademark), Kenalog, and others), laser, photodynamic therapy and others. However, a participant is not eligible if the fellow (study) eye has ever received any of these treatments for advanced AMD.
EXCLUSION CRITERIA:
Ocular disease in either eye, other than AMD, which may confound assessment of the retina, including:
- Diabetic retinopathy unless retinopathy is limited to fewer than 10 microaneurysms and/or small retinal hemorrhages,
- Angioid streaks,
- Central serous choroidopathy,
- Surface wrinkling retinopathy (epiretinal membrane) that is more severe than the mild surface wrinkling retinopathy,
- Optic atrophy,
- Pigmentary abnormalities considered by the Clinical Center ophthalmologist to be less typical of AMD than of some other condition, such as pattern dystrophy or chronic central serous retinopathy,
- Myopic crescent of the optic disc the width of which is greater than or equal to 50 percent of the longest diameter of the disc, or pigmentary abnormalities in the posterior pole considered by the clinic ophthalmologist more likely to be due to myopia than to AMD,
- Macular hole or pseudohole,
- Retinal vein occlusion, active uveitis, presumed ocular histoplasmosis syndrome, other sight-threatening retinopathies, and other retinal degenerations, significant explained or unexplained visual field loss, or any other type of retinopathy or retinal degeneration,
- A choroidal nevus within 2 DD of the center of the macula associated with depigmentation or overlying atypical drusen.
- Epiretinal membrane of significant size located in the macular
area that potentially can cause vision loss.
-Amblyopia (in study eye only)
- Other ocular diseases or conditions, the presence of which may now or in the future complicate evaluation of AMD.
- Previous retinal or other ocular surgical procedures, the effects of which may now or in the future complicate assessment of the progression of AMD. Examples are argon laser trabeculoplasty, radial keratotomy, trabeculectomy, cryosurgery (except to repair a peripheral retinal hole), lamellar keratoplasty, pterygium surgery that affects or threatens the visual axis, radiation for ocular tumor, or repair of corneal or sclera laceration. Cataract surgery more than three months prior to randomization is not an exclusion criterion unless complicated by a condition that is causing or is likely to cause a decrease in visual acuity. Laser photocoagulation for drusen and non-choroidal neovascularization in the non-study eye will not be exclusion factors.
- Chronic requirement for any systemic or ocular medication administered for other diseases such as glaucoma and known to be toxic to the retina, or optic nerve, such as:
- Deferoxamine
- Chloroquine/Hydroxychloroquine (Plaquinil)
- Tamoxifen
- Chlorpromazine
- Phenothiazines
- Chronic systemic steroid use of at least 10 mg per day or more.
- Ethambutol
- Unwillingness or inability to stop taking supplements containing lutein, zeaxanthin, omega-3 LCPUFAs, vitamin C, vitamin E, beta-carotene, zinc or copper during the run-in period and for the next five years, or failure to take at least 75 percent of run-in medication as determined by an estimated count of placebo tablets and capsules (exceptions may be made by appeal to the AREDS2 Coordinating Center).
- Participants supplementing with 2 mg or more of lutein and/or 500 mg or more of omega-3 long-chain polyunsaturated fatty acids (DHA and EPA) for a period of 1 year or more prior to the date of randomization. A participant is eligible for the study if he/she agrees to refrain from taking these supplements during the Qualification period.
- Intraocular pressure 26 mm Hg or higher, or if there is some reason to believe that the participant may have glaucoma (e.g., history of the diagnosis of glaucoma, past or present use of medications to control intraocular pressure, or disc/nerve fiber layer defects suggestive of glaucoma), then the absence of a glaucomatous visual field defect must be documented by a normal Goldmann, Humphrey, or Octopus perimetry test within 6 months prior to qualification (In the judgment of the investigator, the participant may be ineligible due to glaucoma based upon IOP measurements, disc/nerve fiber layer defects suggestive of glaucoma, and visual field abnormalities).
- Cataract surgery within three months or capsulotomy within six weeks prior to the Qualification Visit.
- History of lung cancer.
- Any systemic disease with a poor five-year survival prognosis (e.g. cancer, cardiovascular disease). If a vascular condition appears stable and the initial event occurred more than 12 months ago, the participant is eligible for the study.
- Hemochromatosis, Wilson's Disease, or recent diagnosis of oxalate kidney stones.
- Participant that has any condition that would make adherence or follow-up to the examination schedule of annual intervals for at least five years difficult or unlikely (e.g., personality disorder, use of major tranquilizers such as Haldol or Phenothiazine, chronic alcoholism or drug abuse).
- Current participation in other studies that is likely to affect adherence with the AREDS2 follow-up schedule.
- Participant is taking a systemic anti-angiogenic (such as squalamine lactate, avastin, etc.) for treatment of choroidal neovascularization or cancer. The use of intravitreal anti-VEGF such as Avastin, Lucentis, or Macugen, in the eye that had advanced AMD at baseline is allowed. However, a participant is not eligible if the fellow (study) eye has ever received any of these treatments for advanced AMD.
Citations:
Contacts:
Principal Investigator |
Referral Contact |
For more information: |
| Wai T. Wong, M.D. National Eye Institute (NEI) National Institutes of Health Building 7 Room 238 7 Center Drive Bethesda, Maryland 20892 (301) 496-7821 wongw@mail.nih.gov |
Katherine H. Shimel, R.N. National Eye Institute (NEI) National Institutes of Health Building 10 Room 10S215 10 Center Drive Bethesda, Maryland 20892 (301) 402-2863 shimelk@nei.nih.gov |
Patient Recruitment and Public Liaison Office Building 61 10 Cloister Court Bethesda, Maryland 20892-4754 Toll Free: 1-800-411-1222 TTY: 301-594-9774 (local),1-866-411-1010 (toll free) Fax: 301-480-9793 prpl@mail.cc.nih.gov |
Clinical Trials Number:
NCT00345176
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