VITamin D and omegA-3 triaL (VITAL)

Summary

Principal Investigator: JOANN ELISABETH MANSON
Abstract: DESCRIPTION (provided by applicant): We propose to conduct a large, cost-effective, randomized, double-blind, placebo-controlled, 2x2 factorial trial of vitamin D (in the form of vitamin D3 [cholecalciferol]) and marine omega-3 fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) supplements in the primary prevention of cancer and cardiovascular disease (CVD). Data from laboratory studies, epidemiologic research, small primary prevention trials, and/or large secondary prevention trials strongly suggest that these nutritional agents reduce cancer or CVD risk, but large primary prevention trials with adequate dosing in general populations (i.e., unselected for disease risk) are lacking. Growing enthusiasm for supplemental vitamin D and fish oil underscores the urgent need for a timely initiation of such a trial, before their use becomes so prevalent (through supplements and fortification of the food supply) as to render participant recruitment and hypothesis testing impossible. The proposed trial will be conducted among 20,000 men aged e60 and women aged e65, to be recruited from a mailing to 1.2 million persons, including health and other professionals, members of AARP (formerly known as the American Association of Retired Persons), and others. The mailing will contain a letter describing the trial, an informed consent form, and a questionnaire soliciting information on past medical history, cancer and vascular risk factors, diet, and medication and nutritional supplement use. Willing and eligible respondents will be enrolled in a 3-month run-in, during which they will receive placebos. At the end of the run-in, those who remain willing and eligible, and who report having taken at least two-thirds of the pills, will be randomly assigned to one of four treatment groups for 5 years: vitamin D3 (1600 IU/d) and fish oil (EPA+DHA, 1 g/d);vitamin D3 and fish oil placebo;placebo vitamin D3 and fish oil;and placebo vitamin D3 and placebo fish oil. Blood samples will be collected and stored to allow assessment of effect modification by baseline 25-hydroxyvitamin D and omega-3 fatty acid levels, as well as future ancillary studies of genetic/biochemical hypotheses. At 1-year intervals, participants will receive a new supply of pills and a follow-up questionnaire on compliance, possible side effects, and incidence of endpoints. Endpoints will be confirmed by medical record review. Given our success with prior mail-based large simple trials and cohort studies, as well as results of a pilot study in the intended source population, we believe the trial will be able to provide either definitive positive or informative null results regarding the study hypotheses. PUBLIC HEALTH RELEVANCE: The purported health benefits of vitamin D and marine omega-3 fatty acids are receiving increasing attention in the medical literature and the popular press. However, definitive data on health benefits and risks of these agents are lacking. Findings from this large clinical trial will clarify the role of vitamin D and marine omega-3 fatty acid supplements in the primary prevention of cancer and cardiovascular disease in men and women.
Funding Period: 2009-09-29 - 2014-12-31
more information: NIH RePORT

Top Publications

  1. pmc Does vitamin D affect risk of developing autoimmune disease?: a systematic review
    Martin A Kriegel
    Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA
    Semin Arthritis Rheum 40:512-531.e8. 2011
  2. pmc The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease
    JoAnn E Manson
    Division of Preventive Medicine, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 900 Commonwealth Avenue East, Boston, MA 02215, United States
    Contemp Clin Trials 33:159-71. 2012
  3. pmc Vitamin d and cardiovascular disease
    Jacqueline S Danik
    Division of Preventive Medicine, Brigham and Women s Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA, 02215, USA
    Curr Treat Options Cardiovasc Med 14:414-24. 2012
  4. pmc Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies
    Lu Wang
    Brigham and Women s Hospital, Boston, MA 02215, USA
    Circ Cardiovasc Qual Outcomes 5:819-29. 2012
  5. pmc Effect of vitamin D supplementation on blood pressure in blacks
    John P Forman
    Renal Division and Kidney Clinical Research Institute, Brigham and Women s Hospital, 41 Ave Louis Pasteur, Suite 120, Boston, MA 02115, USA
    Hypertension 61:779-85. 2013
  6. pmc Vitamin D and cardiovascular disease: an appraisal of the evidence
    Peter F Schnatz
    Departments of Obstetrics and Gynecology and
    Clin Chem 60:600-9. 2014
  7. pmc Impact of vitamin D supplementation on inflammatory markers in African Americans: results of a four-arm, randomized, placebo-controlled trial
    Paulette D Chandler
    Division of Preventive Medicine, Brigham and Women s Hospital, 900 Commonwealth Avenue, Third Floor, Boston, MA 02215
    Cancer Prev Res (Phila) 7:218-25. 2014
  8. pmc Risk of hypercalcemia in blacks taking hydrochlorothiazide and vitamin D
    Paulette D Chandler
    Division of Preventive Medicine, Department of Medicine, Brigham and Women s Hospital, Boston, Mass Harvard Medical School, Boston, Mass Electronic address
    Am J Med 127:772-8. 2014

Detail Information

Publications9

  1. pmc Does vitamin D affect risk of developing autoimmune disease?: a systematic review
    Martin A Kriegel
    Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA
    Semin Arthritis Rheum 40:512-531.e8. 2011
    ..We evaluated the epidemiologic evidence that vitamin D may be related to human autoimmune disease risk...
  2. pmc The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease
    JoAnn E Manson
    Division of Preventive Medicine, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 900 Commonwealth Avenue East, Boston, MA 02215, United States
    Contemp Clin Trials 33:159-71. 2012
    ....
  3. pmc Vitamin d and cardiovascular disease
    Jacqueline S Danik
    Division of Preventive Medicine, Brigham and Women s Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA, 02215, USA
    Curr Treat Options Cardiovasc Med 14:414-24. 2012
    ..Ongoing clinical trials seek to address the effects of vitamin D supplementation on CVD and other nonskeletal outcomes...
  4. pmc Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies
    Lu Wang
    Brigham and Women s Hospital, Boston, MA 02215, USA
    Circ Cardiovasc Qual Outcomes 5:819-29. 2012
    ..Vitamin D status has been linked to the risk of cardiovascular disease (CVD). However, the optimal 25-hydroxy-vitamin D (25[OH]-vitamin D) levels for potential cardiovascular health benefits remain unclear...
  5. pmc Effect of vitamin D supplementation on blood pressure in blacks
    John P Forman
    Renal Division and Kidney Clinical Research Institute, Brigham and Women s Hospital, 41 Ave Louis Pasteur, Suite 120, Boston, MA 02115, USA
    Hypertension 61:779-85. 2013
    ....
  6. pmc Vitamin D and cardiovascular disease: an appraisal of the evidence
    Peter F Schnatz
    Departments of Obstetrics and Gynecology and
    Clin Chem 60:600-9. 2014
    ..Few randomized clinical trials of vitamin D supplementation and CHD have been conducted, however, and no trial with CHD as the primary prespecified outcome has been completed...
  7. pmc Impact of vitamin D supplementation on inflammatory markers in African Americans: results of a four-arm, randomized, placebo-controlled trial
    Paulette D Chandler
    Division of Preventive Medicine, Brigham and Women s Hospital, 900 Commonwealth Avenue, Third Floor, Boston, MA 02215
    Cancer Prev Res (Phila) 7:218-25. 2014
    ....
  8. pmc Risk of hypercalcemia in blacks taking hydrochlorothiazide and vitamin D
    Paulette D Chandler
    Division of Preventive Medicine, Department of Medicine, Brigham and Women s Hospital, Boston, Mass Harvard Medical School, Boston, Mass Electronic address
    Am J Med 127:772-8. 2014
    ..Thus, they are more likely to be exposed to vitamin D supplementation and thiazide diuretics. The risk for hypercalcemia among blacks using vitamin D and hydrochlorothiazide is undefined...

Research Grants30

  1. Effect of Vitamin D and Omega-3 Fatty Acids on Blood Pressure and Hypertension
    Howard D Sesso; Fiscal Year: 2013
    ..Because high blood pressure is responsible for one out of every six deaths in the United States, the results of this study could possibly improve the health of many people. ..
  2. VITamin D and OmegA-3 TriaL: Effects on Bone Structure and Architecture
    MERYL SUSAN LEBOFF; Fiscal Year: 2013
    ..Findings from this proposal will fill gaps in knowledge and inform clinical and public health recommendations. ..
  3. Vitamin D and Omega-3 Fatty Acids(VITAL Trial): Effects on Fractures
    MERYL SUSAN LEBOFF; Fiscal Year: 2013
    ....
  4. VITAL-AMD: Prevention of AMD in the VITamin D and OmegA-3 Trial
    Debra A Schaumberg; Fiscal Year: 2013
    ..Findings from this large clinical trial will clarify the role of vitamin D and omega-3 fatty acid supplements in he prevention of AMD, the leading cause of blindness in US men and women. ..
  5. Omega-3 Fatty Acids for Prevention of Dry Eye Disease: VITAL-DED
    Debra A Schaumberg; Fiscal Year: 2013
    ....
  6. Diabetes Prevention in the Vitamin D and Omega-3 Trial
    Yiqing Song; Fiscal Year: 2013
    ....
  7. A Large Randomized Trial of Vitamin D, Omega-3 Fatty Acids and Cognitive Decline
    Jae H Kang; Fiscal Year: 2013
    ..We propose an exciting substudy, incorporating cognitive testing among VITAL participants aged 65+ years to evaluate whether marine omega-3 fatty and vitamin D may be important in the maintenance of cognitive function in men and women. ..
  8. Women's Health Study: Continued Follow-up
    I Min Lee; Fiscal Year: 2013
    ..1 ..
  9. The VITAL Rhythm Study
    Christine M Albert; Fiscal Year: 2013
    ..If either agent significantly lowers AF risk, then these agents would represent one of the first therapies proven effective for the primary prevention of this growing morbid disease. ..
  10. Vitamin D and Fish Oil for Autoimmune Disease, Inflammation and Joint Pain
    Karen H Costenbader; Fiscal Year: 2013
    ....
  11. Comparative Mechanisms of Cancer Chemoprevention
    Roderick H Dashwood; Fiscal Year: 2013
    ..This application is innovative and timely in bridging basic mechanisms, preclinical models, and human studies of epigenetics and diet. ..
  12. Effects of vitamin D and omega-3 fatty acids on infectious diseases and hCAP18
    Carlos A Camargo; Fiscal Year: 2013
    ..The findings may have direct clinical and public health impact for the prevention of infections in older adults. ..
  13. Lung VITamin D and OmegA-3 TriaL (Lung VITAL)
    Diane R Gold; Fiscal Year: 2013
    ..If vitamin D or marine omega-3 fatty acid supplementation reduce COPD and asthma exacerbations, reduce decline of lung function, improve asthma control and/or reduce pneumonia risk, this would be of great benefit to public health. ..
  14. Cumulative Stress and CVD Risk in Middle-Aged and Older Women
    Michelle A Albert; Fiscal Year: 2013
    ..Thus, this proposed study will provide valuable clinical information that can result in the development of behavioral and therapeutic interventions aimed at decreasing the effects of cumulative stressors on CVD health. ..
  15. VITAL-DEP: Depression Endpoint Prevention in the VITamin D and OmegA-3 TriaL
    OLIVIA IFEOMA OKEREKE; Fiscal Year: 2013
    ....
  16. Hopkins Center for Eliminate Cardiovascular Health Disparities
    Lisa A Cooper; Fiscal Year: 2013
    ..abstract_text> ..
  17. Penn TREC Survivor Center
    Kathryn H Schmitz; Fiscal Year: 2013
    ..abstract_text> ..