Age-related Macular Degeneration
Conditions
Keywords
age-related macular degeneration, incidence, progression
Brief summary
The VITamin D and OmegA-3 Trial (VITAL; NCT 01169259) is a randomized clinical trial in 25,875 U.S. men and women investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor fish oil, 1 gram) reduces the risk of developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. This ancillary study is being conducted among participants in VITAL and will examine whether vitamin D or omega-3 fatty acids, compared to placebo, reduce the incidence and/or progression of age-related macular degeneration (AMD).
Detailed description
This ancillary study to the VITamin D and OmegA-3 TriaL (VITAL) will examine whether vitamin D3 and omega-3 fatty acids can help prevent the onset or progression of age-related macular degeneration (AMD). The study will also examine whether vitamin D3 and omega-3 fatty acids interact with each other, or with specific genes associated with AMD or vitamin D3 or omega-3 fatty acid metabolic activity, to affect the risk of developing AMD.
Interventions
Sponsors
National Eye Institute (NEI)
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* All participants in VITAL (NCT 01169259) are eligible to participate in this ancillary study.
Exclusion criteria
* None
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an AMD Event | 5 years | AMD Event = a composite endpoint of incident AMD plus cases of progression to advanced AMD among participants with AMD at baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Incident Visually-Significant AMD | 5 years | AMD responsible for a reduction in best-corrected visual acuity to 20/30 or worse |
| Number of Participants With Incident Advanced AMD | 5 years | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Incident AMD | 5 years | Incident AMD with or without vision loss to 20/30 or worse; a component of the composite end point of AMD Events |
| Number of Participants With AMD Progression | 5 years | Progression to advanced AMD among participants with AMD at baseline; a component of the composite end point of AMD Events |
| Number of Participants With an AMD Event, Excluding the First Two Years of Follow-up | 5 years (excluding the first two years of follow-up) | AMD Event = a composite endpoint of incident AMD plus cases of progression to advanced AMD among participants with AMD at baseline |
Countries
United States
Participant flow
Recruitment details
401605 initially screened; 39430 eligible to enter run-in; 25871 eligible for randomization; 2x2 factorial design: 12927 assigned to active vit D (of these, 6463 were assigned to active omega-3 FAs and 6464 to placebo omega-3 FAs) & 12944 assigned to placebo vit D (of these, 6470 were assigned to active omega-3 FAs and 6474 to placebo omega-3 FAs)
Pre-assignment details
The trial included a 3-month placebo run-in period to select participants likely to have excellent compliance. Only individuals who reported taking at least 2/3 of their study pills during the run-in and met other eligibility criteria were randomized into the trial.
Participants by arm
| Arm | Count |
|---|---|
| Vitamin D + Fish Oil Vitamin D (cholecalciferol), 2000 IU per day
Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg. of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\])
Omega-3 fatty acids (fish oil)
Vitamin D3 | 6,463 |
| Vitamin D + Fish Oil Placebo Vitamin D3 (cholecalciferol), 2000 IU per day
Fish oil placebo
Vitamin D3
Fish oil placebo | 6,464 |
| Vitamin D Placebo + Fish Oil Vitamin D placebo
Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg. of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\])
Omega-3 fatty acids (fish oil)
Vitamin D3 placebo | 6,470 |
| Vitamin D Placebo + Fish Oil Placebo Vitamin D placebo
fish oil placebo
Vitamin D3 placebo
Fish oil placebo | 6,474 |
| Total | 25,871 |
Baseline characteristics
| Characteristic | Vitamin D + Fish Oil Placebo | Vitamin D Placebo + Fish Oil | Vitamin D + Fish Oil | Vitamin D Placebo + Fish Oil Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4002 Participants | 4009 Participants | 4005 Participants | 4007 Participants | 16023 Participants |
| Age, Categorical Between 18 and 65 years | 2462 Participants | 2461 Participants | 2458 Participants | 2467 Participants | 9848 Participants |
| Age, Continuous | 67.1 years STANDARD_DEVIATION 7 | 67.2 years STANDARD_DEVIATION 7.1 | 67.1 years STANDARD_DEVIATION 7.1 | 67.1 years STANDARD_DEVIATION 7.1 | 67.1 years STANDARD_DEVIATION 7.1 |
| Race/Ethnicity, Customized Race/Ethnicity African-American | 1275 Participants | 1271 Participants | 1278 Participants | 1282 Participants | 5106 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Asian/Pacific Islander | 86 Participants | 98 Participants | 102 Participants | 102 Participants | 388 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic (Not African-American) | 270 Participants | 245 Participants | 246 Participants | 252 Participants | 1013 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Native American/Alaskan Native | 56 Participants | 58 Participants | 62 Participants | 52 Participants | 228 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Non-Hispanic White | 4498 Participants | 4529 Participants | 4515 Participants | 4504 Participants | 18046 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Other/Unknown | 133 Participants | 123 Participants | 126 Participants | 141 Participants | 523 Participants |
| Region of Enrollment United States | 6464 participants | 6470 participants | 6463 participants | 6474 participants | 25871 participants |
| Sex: Female, Male Female | 3271 Participants | 3271 Participants | 3276 Participants | 3267 Participants | 13085 Participants |
| Sex: Female, Male Male | 3193 Participants | 3199 Participants | 3187 Participants | 3207 Participants | 12786 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 | 241 / 6,463 | 244 / 6,464 | 252 / 6,470 | 241 / 6,474 |
| other Total, other adverse events | 5,101 / 6,463 | 5,027 / 6,464 | 5,037 / 6,470 | 5,101 / 6,474 |
| serious Total, serious adverse events | 791 / 6,463 | 782 / 6,464 | 822 / 6,470 | 837 / 6,474 |
Outcome results
Primary
Number of Participants With an AMD Event
AMD Event = a composite endpoint of incident AMD plus cases of progression to advanced AMD among participants with AMD at baseline
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Vitamin D | Number of Participants With an AMD Event | 163 Participants |
| Vitamin D Placebo | Number of Participants With an AMD Event | 161 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With an AMD Event | 157 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With an AMD Event | 167 Participants |
p-value: <0.0595% CI: [0.82, 1.27]Regression, Cox
p-value: <0.0595% CI: [0.76, 1.17]Regression, Cox
Secondary
Number of Participants With Incident Advanced AMD
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Vitamin D | Number of Participants With Incident Advanced AMD | 51 Participants |
| Vitamin D Placebo | Number of Participants With Incident Advanced AMD | 42 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With Incident Advanced AMD | 39 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With Incident Advanced AMD | 54 Participants |
p-value: <0.0595% CI: [0.81, 1.84]Regression, Cox
p-value: <0.0595% CI: [0.48, 1.09]Regression, Cox
Secondary
Number of Participants With Incident Visually-Significant AMD
AMD responsible for a reduction in best-corrected visual acuity to 20/30 or worse
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Vitamin D | Number of Participants With Incident Visually-Significant AMD | 73 Participants |
| Vitamin D Placebo | Number of Participants With Incident Visually-Significant AMD | 61 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With Incident Visually-Significant AMD | 61 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With Incident Visually-Significant AMD | 73 Participants |
p-value: <0.0595% CI: [0.86, 1.7]Regression, Cox
p-value: <0.0595% CI: [0.59, 1.17]Regression, Cox
Other Pre-specified
Number of Participants With AMD Progression
Progression to advanced AMD among participants with AMD at baseline; a component of the composite end point of AMD Events
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Vitamin D | Number of Participants With AMD Progression | 15 Participants |
| Vitamin D Placebo | Number of Participants With AMD Progression | 24 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With AMD Progression | 20 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With AMD Progression | 19 Participants |
p-value: <0.0595% CI: [0.33, 1.21]Regression, Cox
p-value: <0.0595% CI: [0.56, 1.97]Regression, Cox
Other Pre-specified
Number of Participants With an AMD Event, Excluding the First Two Years of Follow-up
AMD Event = a composite endpoint of incident AMD plus cases of progression to advanced AMD among participants with AMD at baseline
Time frame: 5 years (excluding the first two years of follow-up)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Vitamin D | Number of Participants With an AMD Event, Excluding the First Two Years of Follow-up | 84 Participants |
| Vitamin D Placebo | Number of Participants With an AMD Event, Excluding the First Two Years of Follow-up | 91 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With an AMD Event, Excluding the First Two Years of Follow-up | 83 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With an AMD Event, Excluding the First Two Years of Follow-up | 92 Participants |
p-value: <0.0595% CI: [0.69, 1.25]Regression, Cox
p-value: <0.0595% CI: [0.67, 1.21]Regression, Cox
Other Pre-specified
Number of Participants With Incident AMD
Incident AMD with or without vision loss to 20/30 or worse; a component of the composite end point of AMD Events
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Vitamin D | Number of Participants With Incident AMD | 148 Participants |
| Vitamin D Placebo | Number of Participants With Incident AMD | 137 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With Incident AMD | 137 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With Incident AMD | 148 Participants |
p-value: <0.0595% CI: [0.86, 1.37]Regression, Cox
p-value: <0.0595% CI: [0.73, 1.17]Regression, Cox