Cataract, Macular Degeneration
Conditions
Keywords
cataract, advanced macular degeneration
Brief summary
RATIONALE: Aging may affect a person's vision. Vitamin E and/or selenium may help prevent cataracts or age-related macular degeneration in men receiving these drugs as part of a clinical trial for the prevention of prostate cancer. PURPOSE: This clinical trial is studying vitamin E and/or selenium to see how well they work in preventing cataract and age-related macular degeneration in men enrolled on SELECT (SWOG-S0000).
Detailed description
OBJECTIVES: Primary * To test whether vitamin E and/or selenium reduces the risk of visually significant age-related macular degeneration (AMD) in men enrolled on SELECT (SWOG-S0000). * To test whether vitamin E and/or selenium reduces the risk of cataract in these participants. Secondary * To test whether vitamin E and/or selenium reduces the risk of advanced AMD in these participants. * To test whether vitamin E and/or selenium reduces the risk of cataract surgery and subtypes in these participants. OUTLINE: This is a multicenter study. Data from medical records obtained from the participant's ophthalmologist or optometrist are reviewed. Information from these records is then used to confirm baseline reports of age-related macular degeneration (AMD) as well as 6-month and annual reports of new diagnoses of AMD and cataract (or cataract surgery) made since the start of this study. Detailed questionnaires are also obtained from the participant's ophthalmologist or optometrist to provide information about the reported AMD or cataract diagnosis (e.g., date of initial diagnosis; best-corrected visual acuity at the time of diagnosis; date when visual acuity was first noted to be 20/30 or worse \[if different from the date of initial diagnosis\]; pathological findings observed when AMD was first diagnosed \[e.g., drusen, retinal pigment epithelial hypo/hyperpigmentation, geographic atrophy, retinal pigment epithelial detachment, subretinal neovascular membrane, or disciform scar\]; pathological findings observed when visual acuity was first noted to be 20/30 or worse; date when exudative \[wet\] AMD was first noted; presence of other ocular abnormalities that could explain or contribute to visual loss; whether AMD or cataract, by itself, are significant enough to cause vision to be reduced to 20/30 or worse; whether laser treatment or photodynamic therapy was performed for AMD; date of cataract extraction; etiology of cataract \[e.g., age-related, traumatic, congenital, inflammatory, or surgery- or steroid-induced\]; and cataract type \[e.g., nuclear, cortical, posterior subcapsular, or other\]).
Interventions
DRUGselenium
200 mcg daily for 7-12 years
DRUGvitamin E
400 IU daily by mouth for 7-12 years
daily for 7-12 years
DRUGselenium placebo
daily for 7-12 years
Sponsors
National Cancer Institute (NCI)
National Eye Institute (NEI)
SWOG Cancer Research Network
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
50 Years to 120 Years
Healthy volunteers
Yes
Inclusion criteria
DISEASE CHARACTERISTICS: * Enrolled on the Selenium and Vitamin E Prostate Cancer Prevention Trial (SELECT) SWOG-S0000 * Diagnosis of 1 of the following: * Age-related macular degeneration (AMD) at baseline or at follow-up * Cataract or a cataract extraction at follow-up (Closed for accrual as of 10/01/29) * Participants with a prior diagnosis of cataract at baseline followed by another cataract event (cataract diagnosis or a cataract extraction) at follow-up are not eligible * Participants with a prior diagnosis of cataract at baseline followed by a diagnosis of AMD at follow-up are eligible PATIENT CHARACTERISTICS: * See Disease Characteristics PRIOR CONCURRENT THERAPY: * Not applicable
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Visually Significant Age-related Macular Degeneration (AMD) | Every 6 months, up to 7 years | Visually significant age-related AMD was defined as incident AMD responsible for reduction in best corrected visual acuity to 20/30 or worse(AMD 20/30) |
| Number of Participants With Cataract and Best Corrected Visual-acuity of 20/30 | Every 6 months, up to 7 years | Incident cataract was defined as lens opacity diagnosed after randomization but prior to end of study, age-related in origin, and best-corrected visual acuity of 20/30 or worse attributable to the opacity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Advanced AMD | Every 6 months, up to 7 years | Advanced AMD was defined as the occurrence of disciform scars, or geographic atrophy or retinal pigment epithelium (RPE) detachment in either or both eyes at AMD diagnosis. |
| Number of Participants Who Underwent Cataract Extraction | Every 6 months, up to 7 years | Cataract extraction was defined as the surgical removal of an incident cataract. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Selenium + Vitamin E Placebo Selenium and vitamin E placebo daily for 7-12 years.
Selenium: 200 mcg daily for 7 - 12 years
Vitamin E placebo: 1 pill by mouth daily for 7 - 12 years | 3,375 |
| Selenium + Vitamin E Selenium and vitamin E daily for 7-12 years. Selenium: 200 mcg daily for 7 - 12 years
Vitamin E: 400 IU daily by mouth for 7 - 12 years | 3,357 |
| Vitamin E Placebo + Selenium Placebo Vitamin E placebo and selenium placebo daily for 7-12 years.
Vitamin E placebo: 1 pill by mouth daily for 7 - 12 years
Selenium placebo: 1 pill by mouth daily for 7 - 12 years | 3,369 |
| Vitamin E + Selenium Placebo Vitamin E and selenium placebo daily for 7-12 years.
Vitamin E: 400 IU daily by mouth for 7 - 12 years
Selenium placebo: 1 pill by mouth daily for 7 - 12 years | 3,374 |
| Total | 13,475 |
Baseline characteristics
| Characteristic | Selenium + Vitamin E Placebo | Selenium + Vitamin E | Vitamin E Placebo + Selenium Placebo | Vitamin E + Selenium Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 62 years | 62 years | 62 years | 62 years | 62 years |
| Age, Customized 50-54 years | 134 Participants | 160 Participants | 159 Participants | 155 Participants | 608 Participants |
| Age, Customized 55-64 years | 1951 Participants | 1964 Participants | 1959 Participants | 2027 Participants | 7901 Participants |
| Age, Customized 65-74 years | 1065 Participants | 1067 Participants | 1061 Participants | 993 Participants | 4186 Participants |
| Age, Customized >=75 years | 225 Participants | 166 Participants | 190 Participants | 199 Participants | 780 Participants |
| Alcohol use >=1 drink/month | 3325 Participants | 3304 Participants | 3303 Participants | 3314 Participants | 13246 Participants |
| Alcohol use Rarely/never | 50 Participants | 51 Participants | 66 Participants | 59 Participants | 226 Participants |
| Alcohol use Unknown | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Aspirin use No | 1891 Participants | 1903 Participants | 1864 Participants | 1893 Participants | 7551 Participants |
| Aspirin use Yes | 1484 Participants | 1454 Participants | 1505 Participants | 1481 Participants | 5924 Participants |
| Body mass index (kg/m^2) <25 | 674 Participants | 666 Participants | 675 Participants | 626 Participants | 2641 Participants |
| Body mass index (kg/m^2) 25-<30 | 1574 Participants | 1607 Participants | 1591 Participants | 1606 Participants | 6378 Participants |
| Body mass index (kg/m^2) >=30 | 1127 Participants | 1084 Participants | 1103 Participants | 1142 Participants | 4456 Participants |
| Cigarette smoking Current | 248 Participants | 278 Participants | 319 Participants | 268 Participants | 1113 Participants |
| Cigarette smoking Former | 1670 Participants | 1654 Participants | 1681 Participants | 1642 Participants | 6647 Participants |
| Cigarette smoking Never | 1451 Participants | 1419 Participants | 1366 Participants | 1457 Participants | 5693 Participants |
| Cigarette smoking Unknown | 6 Participants | 6 Participants | 3 Participants | 7 Participants | 22 Participants |
| Education (highest level) >College graduate | 1759 Participants | 1752 Participants | 1705 Participants | 1738 Participants | 6954 Participants |
| Education (highest level) <= High school graduate or GED | 653 Participants | 641 Participants | 706 Participants | 656 Participants | 2656 Participants |
| Education (highest level) Some college/vocational school | 943 Participants | 943 Participants | 948 Participants | 964 Participants | 3798 Participants |
| Education (highest level) Unknown/missing | 20 Participants | 21 Participants | 10 Participants | 16 Participants | 67 Participants |
| History of diabetes No | 3022 Participants | 3009 Participants | 2989 Participants | 3035 Participants | 12055 Participants |
| History of diabetes Yes | 353 Participants | 348 Participants | 380 Participants | 339 Participants | 1420 Participants |
| History of hypertension No | 2036 Participants | 2037 Participants | 1995 Participants | 2073 Participants | 8141 Participants |
| History of hypertension Yes | 1339 Participants | 1320 Participants | 1374 Participants | 1301 Participants | 5334 Participants |
| Included in AMD analysis No | 27 Participants | 15 Participants | 14 Participants | 30 Participants | 86 Participants |
| Included in AMD analysis Yes | 3348 Participants | 3342 Participants | 3355 Participants | 3344 Participants | 13389 Participants |
| Included in cataract analysis No | 570 Participants | 568 Participants | 540 Participants | 530 Participants | 2208 Participants |
| Included in cataract analysis Yes | 2805 Participants | 2789 Participants | 2829 Participants | 2844 Participants | 11267 Participants |
| Race/Ethnicity, Customized Non-white | 622 Participants | 601 Participants | 619 Participants | 611 Participants | 2453 Participants |
| Race/Ethnicity, Customized White | 2753 Participants | 2756 Participants | 2750 Participants | 2763 Participants | 11022 Participants |
| Records sought No | 2740 Participants | 2733 Participants | 2745 Participants | 2745 Participants | 10963 Participants |
| Records sought Yes | 635 Participants | 624 Participants | 624 Participants | 629 Participants | 2512 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3375 Participants | 3357 Participants | 3369 Participants | 3374 Participants | 13475 Participants |
| Statin use No | 2464 Participants | 2447 Participants | 2451 Participants | 2434 Participants | 9796 Participants |
| Statin use Unknown | 27 Participants | 24 Participants | 18 Participants | 26 Participants | 95 Participants |
| Statin use Yes | 884 Participants | 886 Participants | 900 Participants | 914 Participants | 3584 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 151 / 3,374 | 159 / 3,356 | 150 / 3,366 | 147 / 3,374 |
| other Total, other adverse events | 243 / 3,374 | 243 / 3,356 | 261 / 3,366 | 267 / 3,374 |
| serious Total, serious adverse events | 44 / 3,374 | 41 / 3,356 | 50 / 3,366 | 45 / 3,374 |
Outcome results
Primary
Number of Participants With Cataract and Best Corrected Visual-acuity of 20/30
Incident cataract was defined as lens opacity diagnosed after randomization but prior to end of study, age-related in origin, and best-corrected visual acuity of 20/30 or worse attributable to the opacity.
Time frame: Every 6 months, up to 7 years
Population: Marginal analyses were performed with arms pooled based on active vs. placebo selenium or vitamin E.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AMD: Selenium Active | Number of Participants With Cataract and Best Corrected Visual-acuity of 20/30 | Cataract cases | 185 Participants |
| AMD: Selenium Active | Number of Participants With Cataract and Best Corrected Visual-acuity of 20/30 | non-cataract cases | 5409 Participants |
| AMD: Selenium Placebo | Number of Participants With Cataract and Best Corrected Visual-acuity of 20/30 | non-cataract cases | 5469 Participants |
| AMD: Selenium Placebo | Number of Participants With Cataract and Best Corrected Visual-acuity of 20/30 | Cataract cases | 204 Participants |
| AMD: Vitamin E Active | Number of Participants With Cataract and Best Corrected Visual-acuity of 20/30 | Cataract cases | 197 Participants |
| AMD: Vitamin E Active | Number of Participants With Cataract and Best Corrected Visual-acuity of 20/30 | non-cataract cases | 5436 Participants |
| AMD: Vitamin E Placebo | Number of Participants With Cataract and Best Corrected Visual-acuity of 20/30 | Cataract cases | 192 Participants |
| AMD: Vitamin E Placebo | Number of Participants With Cataract and Best Corrected Visual-acuity of 20/30 | non-cataract cases | 5442 Participants |
p-value: 0.3795% CI: [0.75, 1.11]Regression, Cox
p-value: 0.8195% CI: [0.84, 1.25]Regression, Cox
Primary
Number of Participants With Visually Significant Age-related Macular Degeneration (AMD)
Visually significant age-related AMD was defined as incident AMD responsible for reduction in best corrected visual acuity to 20/30 or worse(AMD 20/30)
Time frame: Every 6 months, up to 7 years
Population: Marginal analyses were performed with arms pooled based on active vs. placebo selenium or vitamin E.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AMD: Selenium Active | Number of Participants With Visually Significant Age-related Macular Degeneration (AMD) | AMD cases | 9 Participants |
| AMD: Selenium Active | Number of Participants With Visually Significant Age-related Macular Degeneration (AMD) | non-AMD cases | 6681 Participants |
| AMD: Selenium Placebo | Number of Participants With Visually Significant Age-related Macular Degeneration (AMD) | non-AMD cases | 6687 Participants |
| AMD: Selenium Placebo | Number of Participants With Visually Significant Age-related Macular Degeneration (AMD) | AMD cases | 12 Participants |
| AMD: Vitamin E Active | Number of Participants With Visually Significant Age-related Macular Degeneration (AMD) | AMD cases | 9 Participants |
| AMD: Vitamin E Active | Number of Participants With Visually Significant Age-related Macular Degeneration (AMD) | non-AMD cases | 6677 Participants |
| AMD: Vitamin E Placebo | Number of Participants With Visually Significant Age-related Macular Degeneration (AMD) | AMD cases | 12 Participants |
| AMD: Vitamin E Placebo | Number of Participants With Visually Significant Age-related Macular Degeneration (AMD) | non-AMD cases | 6691 Participants |
Comparison: Statistical analysis for number of participants with visually significant AMD in SEE sites during pill-taking for seleniump-value: 0.5295% CI: [0.32, 1.79]Regression, Cox
Comparison: Statistical analysis for number of participants with visually significant AMD in SEE sites during pill-taking for vitamin Ep-value: 0.5195% CI: [0.31, 1.77]Regression, Cox
Secondary
Number of Participants Who Underwent Cataract Extraction
Cataract extraction was defined as the surgical removal of an incident cataract.
Time frame: Every 6 months, up to 7 years
Population: Marginal analyses were performed with arms pooled based on active vs. placebo selenium or vitamin E.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AMD: Selenium Active | Number of Participants Who Underwent Cataract Extraction | Cataract extraction cases | 99 Participants |
| AMD: Selenium Active | Number of Participants Who Underwent Cataract Extraction | non-cataract extraction cases | 5495 Participants |
| AMD: Selenium Placebo | Number of Participants Who Underwent Cataract Extraction | non-cataract extraction cases | 5553 Participants |
| AMD: Selenium Placebo | Number of Participants Who Underwent Cataract Extraction | Cataract extraction cases | 120 Participants |
| AMD: Vitamin E Active | Number of Participants Who Underwent Cataract Extraction | Cataract extraction cases | 114 Participants |
| AMD: Vitamin E Active | Number of Participants Who Underwent Cataract Extraction | non-cataract extraction cases | 5519 Participants |
| AMD: Vitamin E Placebo | Number of Participants Who Underwent Cataract Extraction | Cataract extraction cases | 105 Participants |
| AMD: Vitamin E Placebo | Number of Participants Who Underwent Cataract Extraction | non-cataract extraction cases | 5529 Participants |
p-value: 0.1995% CI: [0.64, 1.09]Regression, Cox
p-value: 0.5895% CI: [0.83, 1.41]Regression, Cox
Secondary
Number of Participants With Advanced AMD
Advanced AMD was defined as the occurrence of disciform scars, or geographic atrophy or retinal pigment epithelium (RPE) detachment in either or both eyes at AMD diagnosis.
Time frame: Every 6 months, up to 7 years
Population: Marginal analyses were performed with arms pooled based on active vs. placebo selenium or vitamin E.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AMD: Selenium Active | Number of Participants With Advanced AMD | Advanced AMD cases | 10 Participants |
| AMD: Selenium Active | Number of Participants With Advanced AMD | non-advanced AMD cases | 6680 Participants |
| AMD: Selenium Placebo | Number of Participants With Advanced AMD | non-advanced AMD cases | 6695 Participants |
| AMD: Selenium Placebo | Number of Participants With Advanced AMD | Advanced AMD cases | 4 Participants |
| AMD: Vitamin E Active | Number of Participants With Advanced AMD | Advanced AMD cases | 7 Participants |
| AMD: Vitamin E Active | Number of Participants With Advanced AMD | non-advanced AMD cases | 6679 Participants |
| AMD: Vitamin E Placebo | Number of Participants With Advanced AMD | Advanced AMD cases | 7 Participants |
| AMD: Vitamin E Placebo | Number of Participants With Advanced AMD | non-advanced AMD cases | 6696 Participants |
Comparison: Statistical analysis for number of participants with advanced AMD in SEE sites during pill-taking for seleniump-value: 0.1295% CI: [0.79, 7.98]Regression, Cox
Comparison: Statistical analysis for number of participants with advanced AMD in SEE sites during pill-taking for vitamin Ep-value: 0.9895% CI: [0.35, 2.82]Regression, Cox