Stroke, Vitamin D
Conditions
Keywords
stroke, stroke outcomes, vitamin D, omega-3 fatty acid
Brief summary
The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is a completed randomized clinical trial in 25,875 U.S. men and women which investigated whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduced the risk of developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. Observational follow-up of participants is currently ongoing. The current study is being conducted among participants in VITAL who experience a stroke event during follow-up and will examine whether vitamin D or omega-3 fatty acid supplementation impact post-stroke outcomes.
Detailed description
Stroke is a leading cause of disability and death worldwide and is expected to become an even more prevalent cause of disability in the future as the population ages. Understanding risk factors which may prospectively influence stroke outcomes may help to reduce the morbidity burden of stroke. The VITamin D and OmegA-3 TriaL (VITAL) examined the impact of vitamin D3 (2,000 IU/day cholecalciferol) and omega-3 fatty acids (840 mg eicosapentaenoic acid \[EPA\] + docosahexaenoic acid \[DHA\]) on stroke incidence. However, the parent trial did not examine the impact of these supplements on stroke outcomes. Even if they do not significantly reduce stroke incidence, these supplements may still reduce stroke severity and improve outcomes post-stroke. Given the high morbidity burden of stroke, the impact of these supplements on stroke outcomes is of substantial scientific and public health importance. The first aim of this study is to test whether vitamin D3 or omega-3 fatty acid supplementation reduces the risk of poor functional outcomes as measured at hospital discharge and 6- and 12-months post-stroke. The second aim is to determine whether chronic cerebrovascular changes (white matter hyperintensity volume and cerebral microbleeds) mediate the effect of vitamin D3 or omega-3 fatty acid supplementation on stroke outcomes. Individuals enrolled in VITAL who experience a non-fatal stroke event will be mailed additional questionnaires assessing functional limitations, physical disability, and social disability. Responses from these questionnaires will be used to determine the effect of vitamin D3 or omega-3 fatty acid supplementation on post-stroke outcomes.
Interventions
DIETARY_SUPPLEMENTVitamin D
Dietary Supplement: Vitamin D-3 (cholecalciferol), 2000 IU Other Name: cholecalciferol
DRUGFish oil
Drug: Omega-3 fatty acids (fish oil) 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 \[DHA\])
DIETARY_SUPPLEMENTVitamin D placebo
Vitamin D placebo
DRUGFish oil placebo
Fish oil placebo
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
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
No
Inclusion criteria
* Participants eligible and willing to participate in the main VITAL trial (NCT 01169259) who experience a stroke during follow-up.
Exclusion criteria
* Participants eligible and willing to participate in the main VITAL trial (NCT 01169259) who do not experience a stroke during follow-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Poor Stroke Outcome at Hospital Discharge as Measured by the Modified Rankin Scale (mR 3-6) | 1 day | modified Rankin Scale (mRS) at hospital discharge The mRS is often seen as a measure of disability or a global health index due to its strong emphasis on mobility although it claims to be a measure of handicap. The mRS is a seven-point scale (0=no symptoms at all; 1=no significant disability despite symptoms; 2=slight disability; 3=moderate disability; 4=moderately severe disability; 5=severe disability; 6=death). To avoid issues with model convergence due to sparse data, I will a priori categorize the mRS into good (mRS 0-2) versus poor (mRS 3-6) outcomes. These data were collected during the parent study (NCT01169259) |
| Number of Participants With at Least One Functional Limitation After Stroke According to the Scale Adapted From Nagi | 1 year | Functional limitations will be assessed through self-report using the physical performance scale adapted from Nagi. The adapted Nagi scale asks respondents if they experience any limitations in each of the following items: pulling or pushing large objects; stooping, crouching, or kneeling; reaching or extending arms above shoulder level; reaching or extending arms below shoulder level; writing or handling or fingering small objects; standing in one place for long periods; and sitting for an hour. Participants reporting a limitation in any of these items will be considered to have at least one functional limitation after stroke. |
| Number of Participants With a Physical Disability After Stroke as Measured by the Modified Katz Activities of Daily Living (ADL) Scale | 1 year | The modified Katz ADL scale ask participants to self-report if they need needing help with any of the following items: bathing; dressing; eating; getting in and out of a chair; and walking 50 yards. Individuals who report needing help with any of those items will be considered to have a physical disability after stroke. |
| Number of Participants With a Physical Disability After Stroke as Measured by the Rosow-Breslau Functional Health Scale | 1 year | The Rosow-Breslau Functional Health Scale asks participants to self-report if they need help with any of the following tasks: walking 0.5 mile; walking up and down stairs to the second floor; and doing heavy work around the house. Individuals who report needing help with any of those tasks will be considered to have a physical disability after stroke. |
| Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | 1 year | Social disability was assessed through a self-administered questionnaire which asked questions about social functioning developed in the Framingham Heart Study. The scale covers five social areas (housekeeping, transportation, social interaction, food preparation, and grocery shopping). Respondents are grouped into four categories (need met, no apparent problem (best outcome); need met, potential problem; uncertain need met, potential problem; need unmet, current problem (worst outcome)) for each social area using a previously published algorithm. We created summary indices for the total number of unmet needs across all areas and for the total number of unmet needs or uncertain needs met, potential problem. These indices range from 0 to 5, but to avoid problems with model convergence due to sparse data, we will a priori categorize them as 0 (best outcome), 1, or ≥2 (worst outcome). |
Participant flow
Pre-assignment details
This study only enrolled individuals from the main VITAL study who experienced a stroke during the main VITAL study. Therefore, although the main VITAL study enrolled 25871 individuals, the current study only includes the 290 individuals who experienced a stroke event during the main VITAL study.
Participants by arm
| Arm | Count |
|---|---|
| Vitamin D + Fish Oil Vitamin D: Dietary Supplement: Vitamin D-3 (cholecalciferol), 2000 IU Other Name: cholecalciferol
Fish oil: Drug: Omega-3 fatty acids (fish oil) 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 \[DHA\]) | 66 |
| Vitamin D + Fish Oil Placebo Vitamin D: Dietary Supplement: Vitamin D-3 (cholecalciferol), 2000 IU Other Name: cholecalciferol
Fish oil placebo: Fish oil placebo | 75 |
| Vitamin D Placebo + Fish Oil Fish oil: Drug: Omega-3 fatty acids (fish oil) 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 \[DHA\])
Vitamin D placebo: Vitamin D placebo | 82 |
| Vitamin D Placebo + Fish Oil Placebo Vitamin D placebo: Vitamin D placebo
Fish oil placebo: Fish oil placebo | 67 |
| Total | 290 |
Baseline characteristics
| Characteristic | Total | Vitamin D + Fish Oil | Vitamin D + Fish Oil Placebo | Vitamin D Placebo + Fish Oil | Vitamin D Placebo + Fish Oil Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 72.0 years STANDARD_DEVIATION 8.2 | 71.5 years STANDARD_DEVIATION 9.4 | 72.6 years STANDARD_DEVIATION 8.5 | 71.6 years STANDARD_DEVIATION 7.3 | 72.6 years STANDARD_DEVIATION 7.8 |
| Functional limitation at baseline | 20 Participants | 4 Participants | 6 Participants | 7 Participants | 3 Participants |
| Race/Ethnicity, Customized African American | 46 Participants | 9 Participants | 11 Participants | 17 Participants | 9 Participants |
| Race/Ethnicity, Customized American Indian/Alaskan Native | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic, Non-African American | 8 Participants | 5 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Missing | 10 Participants | 3 Participants | 4 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Non-hispanic white | 215 Participants | 46 Participants | 57 Participants | 61 Participants | 51 Participants |
| Race/Ethnicity, Customized Other/Unknown | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Female | 148 Participants | 34 Participants | 38 Participants | 44 Participants | 32 Participants |
| Sex: Female, Male Male | 142 Participants | 32 Participants | 37 Participants | 38 Participants | 35 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 | 7 / 66 | 4 / 75 | 7 / 82 | 4 / 67 |
| other Total, other adverse events | 16 / 66 | 16 / 75 | 17 / 82 | 15 / 67 |
| serious Total, serious adverse events | 18 / 66 | 20 / 75 | 28 / 82 | 19 / 67 |
Outcome results
Primary
Number of Participants With a Physical Disability After Stroke as Measured by the Modified Katz Activities of Daily Living (ADL) Scale
The modified Katz ADL scale ask participants to self-report if they need needing help with any of the following items: bathing; dressing; eating; getting in and out of a chair; and walking 50 yards. Individuals who report needing help with any of those items will be considered to have a physical disability after stroke.
Time frame: 1 year
Population: The overall Number of Participants Analyzed is less than the number of participants in the Participant Flow module because some individuals were missing information on this outcome. Individuals missing information on this outcome include those who experienced a fatal stroke and those who did not return the questionnaire assessing post-stroke outcomes which was mailed to stroke survivors.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Vitamin D | Number of Participants With a Physical Disability After Stroke as Measured by the Modified Katz Activities of Daily Living (ADL) Scale | 6 Participants |
| Vitamin D Placebo | Number of Participants With a Physical Disability After Stroke as Measured by the Modified Katz Activities of Daily Living (ADL) Scale | 6 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With a Physical Disability After Stroke as Measured by the Modified Katz Activities of Daily Living (ADL) Scale | 3 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With a Physical Disability After Stroke as Measured by the Modified Katz Activities of Daily Living (ADL) Scale | 9 Participants |
Primary
Number of Participants With a Physical Disability After Stroke as Measured by the Rosow-Breslau Functional Health Scale
The Rosow-Breslau Functional Health Scale asks participants to self-report if they need help with any of the following tasks: walking 0.5 mile; walking up and down stairs to the second floor; and doing heavy work around the house. Individuals who report needing help with any of those tasks will be considered to have a physical disability after stroke.
Time frame: 1 year
Population: The overall Number of Participants Analyzed is less than the number of participants in the Participant Flow module because some individuals were missing information on this outcome. Individuals missing information on this outcome include those who experienced a fatal stroke and those who did not return the questionnaire assessing post-stroke outcomes which was mailed to stroke survivors.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Vitamin D | Number of Participants With a Physical Disability After Stroke as Measured by the Rosow-Breslau Functional Health Scale | 45 Participants |
| Vitamin D Placebo | Number of Participants With a Physical Disability After Stroke as Measured by the Rosow-Breslau Functional Health Scale | 53 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With a Physical Disability After Stroke as Measured by the Rosow-Breslau Functional Health Scale | 42 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With a Physical Disability After Stroke as Measured by the Rosow-Breslau Functional Health Scale | 56 Participants |
Primary
Number of Participants With at Least One Functional Limitation After Stroke According to the Scale Adapted From Nagi
Functional limitations will be assessed through self-report using the physical performance scale adapted from Nagi. The adapted Nagi scale asks respondents if they experience any limitations in each of the following items: pulling or pushing large objects; stooping, crouching, or kneeling; reaching or extending arms above shoulder level; reaching or extending arms below shoulder level; writing or handling or fingering small objects; standing in one place for long periods; and sitting for an hour. Participants reporting a limitation in any of these items will be considered to have at least one functional limitation after stroke.
Time frame: 1 year
Population: The overall Number of Participants Analyzed is less than the number of participants in the Participant Flow module because some individuals were missing information on this outcome. Individuals missing information on this outcome include those who experienced a fatal stroke and those who did not return the questionnaire assessing post-stroke outcomes which was mailed to stroke survivors.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Vitamin D | Number of Participants With at Least One Functional Limitation After Stroke According to the Scale Adapted From Nagi | 24 Participants |
| Vitamin D Placebo | Number of Participants With at Least One Functional Limitation After Stroke According to the Scale Adapted From Nagi | 27 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With at Least One Functional Limitation After Stroke According to the Scale Adapted From Nagi | 20 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With at Least One Functional Limitation After Stroke According to the Scale Adapted From Nagi | 31 Participants |
Primary
Number of Participants With Poor Stroke Outcome at Hospital Discharge as Measured by the Modified Rankin Scale (mR 3-6)
modified Rankin Scale (mRS) at hospital discharge The mRS is often seen as a measure of disability or a global health index due to its strong emphasis on mobility although it claims to be a measure of handicap. The mRS is a seven-point scale (0=no symptoms at all; 1=no significant disability despite symptoms; 2=slight disability; 3=moderate disability; 4=moderately severe disability; 5=severe disability; 6=death). To avoid issues with model convergence due to sparse data, I will a priori categorize the mRS into good (mRS 0-2) versus poor (mRS 3-6) outcomes. These data were collected during the parent study (NCT01169259)
Time frame: 1 day
Population: The overall Number of Participants Analyzed is less than the number of participants in the Participant Flow module because the mRS was missing for some participants.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active Vitamin D | Number of Participants With Poor Stroke Outcome at Hospital Discharge as Measured by the Modified Rankin Scale (mR 3-6) | Good outcome (mRS 0-2) | 84 Participants |
| Active Vitamin D | Number of Participants With Poor Stroke Outcome at Hospital Discharge as Measured by the Modified Rankin Scale (mR 3-6) | Poor outcome (mRS 3-6) | 43 Participants |
| Vitamin D Placebo | Number of Participants With Poor Stroke Outcome at Hospital Discharge as Measured by the Modified Rankin Scale (mR 3-6) | Poor outcome (mRS 3-6) | 32 Participants |
| Vitamin D Placebo | Number of Participants With Poor Stroke Outcome at Hospital Discharge as Measured by the Modified Rankin Scale (mR 3-6) | Good outcome (mRS 0-2) | 99 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With Poor Stroke Outcome at Hospital Discharge as Measured by the Modified Rankin Scale (mR 3-6) | Good outcome (mRS 0-2) | 96 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With Poor Stroke Outcome at Hospital Discharge as Measured by the Modified Rankin Scale (mR 3-6) | Poor outcome (mRS 3-6) | 33 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With Poor Stroke Outcome at Hospital Discharge as Measured by the Modified Rankin Scale (mR 3-6) | Good outcome (mRS 0-2) | 87 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With Poor Stroke Outcome at Hospital Discharge as Measured by the Modified Rankin Scale (mR 3-6) | Poor outcome (mRS 3-6) | 42 Participants |
Primary
Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale
Social disability was assessed through a self-administered questionnaire which asked questions about social functioning developed in the Framingham Heart Study. The scale covers five social areas (housekeeping, transportation, social interaction, food preparation, and grocery shopping). Respondents are grouped into four categories (need met, no apparent problem (best outcome); need met, potential problem; uncertain need met, potential problem; need unmet, current problem (worst outcome)) for each social area using a previously published algorithm. We created summary indices for the total number of unmet needs across all areas and for the total number of unmet needs or uncertain needs met, potential problem. These indices range from 0 to 5, but to avoid problems with model convergence due to sparse data, we will a priori categorize them as 0 (best outcome), 1, or ≥2 (worst outcome).
Time frame: 1 year
Population: The overall Number of Participants Analyzed is less than the number of participants in the Participant Flow module because some individuals were missing information on this outcome. Individuals missing information on this outcome include those who experienced a fatal stroke and those who did not return the questionnaire assessing post-stroke outcomes which was mailed to stroke survivors.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Active Vitamin D | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Unmet need | 0 | 81 Participants |
| Active Vitamin D | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Unmet need | 1 | 10 Participants |
| Active Vitamin D | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Unmet need | 2 | 3 Participants |
| Active Vitamin D | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Uncertain need met or unmet need | 0 | 59 Participants |
| Active Vitamin D | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Uncertain need met or unmet need | 1 | 19 Participants |
| Active Vitamin D | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Uncertain need met or unmet need | 2 | 16 Participants |
| Vitamin D Placebo | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Uncertain need met or unmet need | 2 | 10 Participants |
| Vitamin D Placebo | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Uncertain need met or unmet need | 0 | 79 Participants |
| Vitamin D Placebo | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Unmet need | 0 | 98 Participants |
| Vitamin D Placebo | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Unmet need | 2 | 2 Participants |
| Vitamin D Placebo | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Unmet need | 1 | 5 Participants |
| Vitamin D Placebo | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Uncertain need met or unmet need | 1 | 16 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Unmet need | 1 | 5 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Unmet need | 2 | 2 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Uncertain need met or unmet need | 0 | 74 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Uncertain need met or unmet need | 2 | 12 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Uncertain need met or unmet need | 1 | 13 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Unmet need | 0 | 92 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Uncertain need met or unmet need | 1 | 22 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Uncertain need met or unmet need | 2 | 14 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Unmet need | 1 | 10 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Uncertain need met or unmet need | 0 | 64 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Unmet need | 0 | 87 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With Social Disability After Stroke as Measured by FHS Social Disability Scale | Unmet need | 2 | 3 Participants |