Clincosm LogoSign in Get a demo

VITamin D and OmegA-3 TriaL: Effects on Bone Structure and Architecture (VITAL)

Sponsor
Brigham and Women's Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT01747447
Collaborator
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (NIH)
771
Enrollment
1
Location
4
Arms
64
Actual Duration (Months)
12
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is a randomized clinical trial in 25,871 U.S. men and women investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or fish oil (1 gram of omega-3 fatty acids) 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 a sub-cohort of 771 participants in VITAL and will test the efficacy and safety of high-dose vitamin D supplementation vs. placebo on skeletal health and body composition.

Condition or Disease Intervention/Treatment Phase
  • Dietary Supplement: Vitamin D3 placebo
  • Dietary Supplement: Fish oil placebo
  • Drug: omega-3 fatty acids (fish oil)
  • Dietary Supplement: Vitamin D3
 N/A

Detailed Description

The VITAL: Effects on Bone Structure and Architecture is an ancillary study of the parent VITAL. This study has enrolled a sub-cohort of 771 VITAL participants at the NIH-sponsored Harvard Catalyst Clinical and Translational Science Center (CTSC). The following measurements will be performed at baseline and 2 years post-randomization to determine whether high-dose vitamin D supplementation vs. placebo: 1) produces small increases or reduces bone loss in spine, hip, and total body areal bone density as assessed by dual x-ray absorptiometry (DXA); 2) reduces bone turnover as assessed by biomarkers of bone resorption and formation; 3) improves (a) volumetric bone mineral density (vBMD) and measures of bone structure as assessed by peripheral quantitative computed tomography (pQCT) and (b) bone microarchitecture as assessed by high resolution pQCT (HR-pQCT) at the distal radius and tibia as well as trabecular bone score (TBS) at the spine; and 4) results in changes in body composition as assessed by DXA. Parallel assessments of the effects of omega-3 fatty acids will be performed. This study may elucidate the mechanisms through which high-dose vitamin D may prevent age-related fractures and provide new insights into the role of vitamin D on skeletal health and body composition.

We are currently analyzing the effects of daily dietary supplements of fish oil (1 gram of omega-3 fatty acids) vs. placebo on skeletal health and body composition.

Study Design

Study Type:
Interventional
Actual Enrollment :
771 participants
Allocation:
Randomized
Intervention Model:
Factorial Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
Double Blind
Primary Purpose:
Prevention
Official Title:
VITamin D and OmegA-3 TriaL: Effects on Bone Structure and Architecture
Actual Study Start Date :
Aug 1, 2012
Actual Primary Completion Date :
Dec 1, 2017
Actual Study Completion Date :
Dec 1, 2017

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Vitamin D placebo + fish oil placebo

Dietary Supplement: Vitamin D3 placebo
Vitamin D placebo

Dietary Supplement: Fish oil placebo
Fish oil placebo
Active Comparator: Vitamin D placebo + fish oil

Dietary Supplement: Vitamin D3 placebo
Vitamin D placebo

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]).
Active Comparator: Vitamin D + fish oil placebo

Dietary Supplement: Fish oil placebo
Fish oil placebo

Dietary Supplement: Vitamin D3
Vitamin D3 (cholecalciferol), 2000 IU per day.
Other Names:
  • cholecalciferol

    		•
    Active Comparator: Vitamin D + 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]).

    Dietary Supplement: Vitamin D3
    Vitamin D3 (cholecalciferol), 2000 IU per day.
    Other Names:
  • cholecalciferol

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in Bone Density [2 years]

      To determine whether vitamin D supplementation produces small increases or reduces bone loss in spine, hip, and total body areal bone density, as assessed by DXA.

    2. Bone Turnover [2 years]

      To determine whether vitamin D supplementation reduces bone turnover, as assessed biomarkers of bone resorption (Collagen Type 1 c-telopeptide) and bone formation (propeptide of type 1 collagen). We are still finalizing analyses for biomarkers of bone resorption (Collagen Type 1 c-telopeptide) and bone formation (propeptide of type 1 collagen). Blood samples have been collected and assays and analyses are in progress.

    Secondary Outcome Measures

    1. Change in Bone Structure [2 years]

      To determine whether vitamin D supplementation results in changes in bone structure.

    Other Outcome Measures

    1. Body Composition [2 years]

      To determine whether vitamin D supplementation results in changes in body composition as assessed by DXA: total body fat and lean mass, and fat mass index and lean mass index, regional fat and lean mass and derived ratios.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes

    Participants in VITAL (NCT 01169259) who meet the following criteria are eligible to participate in this ancillary study:

    • Those who are using bisphosphonates currently or within the past 2 years, or other bone-active medications currently or within the past year are not eligible for this study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Brigham and Women's Hospital Boston Massachusetts United States 02115

    Sponsors and Collaborators

    • Brigham and Women's Hospital
    • National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

    Investigators

    • Principal Investigator: Meryl S LeBoff, M.D., Brigham and Women's Hospital

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Meryl LeBoff, Director of Skeletal Health and Osteoporosis Center, Brigham and Women's Hospital
    ClinicalTrials.gov Identifier:
    NCT01747447
    Other Study ID Numbers:
    • 2012P000560
    • 1R01AR059775-01A1
    • 5R01AR060574-03
    First Posted:
    Dec 11, 2012
    Last Update Posted:
    Feb 3, 2022
    Last Verified:
    Feb 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Vitamin D
    Ergocalciferols
    Cholecalciferol
    Vitamins

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Vitamin D Group Placebo Group
    Arm/Group Description Received active Vitamin D Received placebo Vitamin D
    Period Title: Overall Study
    STARTED 388 383
    COMPLETED 347 340
    NOT COMPLETED 41 43

    Baseline Characteristics

    Arm/Group Title Vitamin D Group Placebo Group Total
    Arm/Group Description Received active Vitamin D Received placebo Vitamin D Total of all reporting groups
    Overall Participants 388 383 771
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    236
    60.8%
    230
    60.1%
    466
    60.4%
    >=65 years
    152
    39.2%
    153
    39.9%
    305
    39.6%
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    63.7
    (6.0)
    63.9
    (6.3)
    63.8
    (6.1)
    Sex: Female, Male (Count of Participants)
    Female
    179
    46.1%
    181
    47.3%
    360
    46.7%
    Male
    209
    53.9%
    202
    52.7%
    411
    53.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    13
    3.4%
    16
    4.2%
    29
    3.8%
    Not Hispanic or Latino
    355
    91.5%
    348
    90.9%
    703
    91.2%
    Unknown or Not Reported
    20
    5.2%
    19
    5%
    39
    5.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    2
    0.5%
    3
    0.8%
    5
    0.6%
    Asian
    9
    2.3%
    6
    1.6%
    15
    1.9%
    Native Hawaiian or Other Pacific Islander
    NA
    NaN
    NA
    NaN
    NA
    NaN
    Black or African American
    40
    10.3%
    38
    9.9%
    78
    10.1%
    White
    317
    81.7%
    313
    81.7%
    630
    81.7%
    More than one race
    6
    1.5%
    3
    0.8%
    9
    1.2%
    Unknown or Not Reported
    9
    2.3%
    3
    0.8%
    12
    1.6%
    Region of Enrollment (Count of Participants)
    United States
    388
    100%
    383
    100%
    771
    100%
    Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    27.2
    (4.7)
    27.3
    (4.8)
    27.2
    (4.8)
    Fat Mass Index (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    10.26
    (4.03)
    10.28
    (3.74)
    10.27
    (3.89)
    Leisure Time Physical Activity (hr/wk) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [hr/wk]
    21.61
    20.99
    21.47
    Diabetes History (Count of Participants)
    Count of Participants [Participants]
    44
    11.3%
    40
    10.4%
    84
    10.9%
    Current Smoking (Count of Participants)
    Count of Participants [Participants]
    26
    6.7%
    22
    5.7%
    48
    6.2%
    Any Fracture History (Count of Participants)
    Count of Participants [Participants]
    32
    8.2%
    29
    7.6%
    61
    7.9%
    Parental History of Hip Fracture (Count of Participants)
    Count of Participants [Participants]
    54
    13.9%
    48
    12.5%
    102
    13.2%
    Baseline Calcium Supplement Use (Count of Participants)
    Count of Participants [Participants]
    69
    17.8%
    63
    16.4%
    132
    17.1%
    Baseline Vitamin D Use (Count of Participants)
    Count of Participants [Participants]
    157
    40.5%
    169
    44.1%
    326
    42.3%
    Baseline Total 25(OH)D (nmol/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [nmol/L]
    67.4
    (22.2)
    71.1
    (23.2)
    69.1
    (22.7)
    Baseline Free 25(OH)D (pmol/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pmol/L]
    14.4
    (4.5)
    14.8
    (4.8)
    14.6
    (4.7)

    Outcome Measures

    1. Primary Outcome
    Title Change in Bone Density
    Description To determine whether vitamin D supplementation produces small increases or reduces bone loss in spine, hip, and total body areal bone density, as assessed by DXA.
    Time Frame 2 years

    Outcome Measure Data

    Analysis Population Description
    Some measurements were excluded due to metal artifacts, severe osteoarthritis, severe scoliosis, degenerative disc disease, and bilateral breast implants.
    Arm/Group Title Vitamin D Group Placebo Group
    Arm/Group Description Received active Vitamin D Received placebo Vitamin D
    Measure Participants 388 383
    Baseline Spine Areal Bone Mineral Density
    1.022
    (0.161)
    1.022
    (0.169)
    Year 2 Spine Areal Bone Mineral Density
    1.028
    (0.164)
    1.028
    (0.171)
    Baseline Femoral Neck Hip Areal Bone Mineral Density
    0.767
    (0.129)
    0.765
    (0.125)
    Year 2 Femoral Neck Hip Areal Bone Mineral Density
    0.765
    (0.131)
    0.766
    (0.124)
    Baseline Total Hip Areal Bone Mineral Density
    0.936
    (0.145)
    0.934
    (0.149)
    Year 2 Total Hip Areal Bone Mineral Density
    0.931
    (0.150)
    0.935
    (0.148)
    Baseline Whole Body Areal Bone Mineral Density
    1.152
    (0.131)
    1.146
    (0.130)
    Year 2 Whole Body Areal Bone Mineral Density
    1.154
    (0.132)
    1.153
    (0.127)
    2. Primary Outcome
    Title Bone Turnover
    Description To determine whether vitamin D supplementation reduces bone turnover, as assessed biomarkers of bone resorption (Collagen Type 1 c-telopeptide) and bone formation (propeptide of type 1 collagen). We are still finalizing analyses for biomarkers of bone resorption (Collagen Type 1 c-telopeptide) and bone formation (propeptide of type 1 collagen). Blood samples have been collected and assays and analyses are in progress.
    Time Frame 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    3. Secondary Outcome
    Title Change in Bone Structure
    Description To determine whether vitamin D supplementation results in changes in bone structure.
    Time Frame 2 years

    Outcome Measure Data

    Analysis Population Description
    Some participants excluded due to motion
    Arm/Group Title Vitamin D Group Placebo Group
    Arm/Group Description Received active Vitamin D Received placebo Vitamin D
    Measure Participants 388 383
    Baseline Total Volumetric Bone Mineral Density at the Radius
    369.678
    (69.484)
    373.903
    (72.498)
    Year 2 Total Volumetric Bone Mineral Density at the Radius
    376.236
    (74.480)
    382.252
    (71.676)
    Baseline Trabecular Volumetric Bone Mineral Density at the Radius
    196.447
    (43.156)
    202.796
    (46.074)
    Year 2 Trabecular Volumetric Bone Mineral Density at the Radius
    199.563
    (44.647)
    205.112
    (46.019)
    Baseline Cortical Volumetric Bone Mineral Density at the Radius
    1197.75
    (31.572)
    1196.98
    (30.816)
    Year 2 Cortical Volumetric Bone Mineral Density at the Radius
    1199.41
    (33.686)
    1201.55
    (30.098)
    Baseline Total Volumetric Bone Mineral Density at the Tibia
    295.291
    (48.045)
    299.232
    (49.285)
    Year 2 Total Volumetric Bone Mineral Density at the Tibia
    296.756
    (49.312)
    303.213
    (48.755)
    Baseline Trabecular Volumetric Bone Mineral Density at the Tibia
    246.626
    (40.741)
    250.139
    (42.283)
    Year 2 Trabecular Volumetric Bone Mineral Density at the Tibia
    249.300
    (41.539)
    254.067
    (42.019)
    Baseline Cortical Volumetric Bone Mineral Density at the Tibia
    1167.39
    (32.258)
    1162.02
    (30.375)
    Year 2 Cortical Volumetric Bone Mineral Density at the Tibia
    1169.98
    (32.739)
    1166.38
    (30.624)
    4. Other Pre-specified Outcome
    Title Body Composition
    Description To determine whether vitamin D supplementation results in changes in body composition as assessed by DXA: total body fat and lean mass, and fat mass index and lean mass index, regional fat and lean mass and derived ratios.
    Time Frame 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Vitamin D Group Placebo Group
    Arm/Group Description Received active Vitamin D Received placebo Vitamin D
    Measure Participants 388 383
    Body Mass Index
    28.3
    (5.1)
    28.3
    (5.2)
    Fat Mass Index
    10.3
    (4.04)
    10.3
    (3.74)
    Lean Mass Index
    16.5
    (2.3)
    16.5
    (2.5)

    Adverse Events

    Time Frame Baseline - 2 years
    Adverse Event Reporting Description
    Arm/Group Title Vitamin D Group Placebo Group
    Arm/Group Description Received active Vitamin D Received placebo Vitamin D
    All Cause Mortality
    Vitamin D Group Placebo Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/388 (2.1%) 3/383 (0.8%)
    Serious Adverse Events
    Vitamin D Group Placebo Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 39/388 (10.1%) 37/383 (9.7%)
    Cardiac disorders
    Major Cardiovascular Events 7/388 (1.8%) 4/383 (1%)
    Endocrine disorders
    Hypercalcemia 3/388 (0.8%) 5/383 (1.3%)
    Gastrointestinal disorders
    Gastrointestinal Bleeding 10/388 (2.6%) 10/383 (2.6%)
    General disorders
    Malignant Cancer 22/388 (5.7%) 19/383 (5%)
    Other (Not Including Serious) Adverse Events
    Vitamin D Group Placebo Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 301/388 (77.6%) 280/383 (73.1%)
    Endocrine disorders
    Parathyroid Condition 1/388 (0.3%) 4/383 (1%)
    Gastrointestinal disorders
    Stomach Pain 145/388 (37.4%) 128/383 (33.4%)
    Nausea 88/388 (22.7%) 77/383 (20.1%)
    Constipation 121/388 (31.2%) 133/383 (34.7%)
    General disorders
    Frequent Nosebleeds 10/388 (2.6%) 20/383 (5.2%)
    Renal and urinary disorders
    Kidney Stones 17/388 (4.4%) 11/383 (2.9%)
    Kidney Failure or Dialysis 1/388 (0.3%) 0/383 (0%)
    Blood in Urine 18/388 (4.6%) 27/383 (7%)
    Skin and subcutaneous tissue disorders
    Easy Bruising 62/388 (16%) 61/383 (15.9%)

    Limitations/Caveats

    Timeline limited to 2 years of follow-up; results not adjusted for multiple hypothesis testing, so findings from the secondary and subgroup analyses are exploratory; results are not generalizable to younger individuals or adults with osteoporosis. Analyses of effects of fish oil supplementation against placebo on these outcomes are in progress.

    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 Meryl S LeBoff, M.D.
    Organization Brigham and Women's Hospital
    Phone 1-800-388-3963
    Email vitalstudy@partners.org
    Responsible Party:
    Meryl LeBoff, Director of Skeletal Health and Osteoporosis Center, Brigham and Women's Hospital
    ClinicalTrials.gov Identifier:
    NCT01747447
    Other Study ID Numbers:
    • 2012P000560
    • 1R01AR059775-01A1
    • 5R01AR060574-03
    First Posted:
    Dec 11, 2012
    Last Update Posted:
    Feb 3, 2022
    Last Verified:
    Feb 1, 2022