A Large Randomized Trial of Vitamin D, Omega-3 Fatty Acids and Cognitive Decline

Summary

Principal Investigator: Jae H Kang
Abstract: DESCRIPTION (provided by applicant): The VITAL (VITamin D and OmegA-3 TriaL) study was recently funded (recruitment starts January 2010) to investigate the effects of vitamin D and marine omega-3 fatty acid supplements on the primary prevention of cardiovascular disease and cancer. We propose to initiate a substudy of cognitive decline (VITAL-Cog) among 3000 participants aged 65+years, including 1000 African-Americans. This is an exciting opportunity to conduct a large and highly cost-effective randomized double-blind placebo-controlled 2x2 factorial trial of vitamin D (vitamin D3 [cholecalciferol], 2000 IU/day) and marine omega-3 fatty acid (docosahexaenoic acid + eicosapentaenoic acid, 1000 mg/day) supplements for slowing cognitive decline. Data from laboratory studies, epidemiologic research, small primary prevention trials, and/or large secondary prevention trials suggest that these nutritional agents may reduce cognitive decline, but large trials among a generally healthy aging population are lacking. Growing public enthusiasm for supplemental vitamin D as well as fish oil underscores the urgent need for a timely initiation of such a trial, before their use becomes sufficiently prevalent (through supplements and food fortification). VITAL participants will be recruited from the general population by mail among health and other professionals, members of AARP, subscribers to Essence magazine, and others;African-Americans will be oversampled, as they have a higher prevalence of vitamin D deficiency. Respondents will be enrolled in a 3-month placebo run-in phase to test participation. We propose to administer baseline telephone cognitive testing during the run-in period, permitting a pre-randomization assessment. The telephone cognitive battery will include 7 tests of general cognition, verbal memory, and executive function (we have extensive experience with telephone cognitive testing, and the battery will be validated in 300 VITAL-Cog participants with in-person cognitive tests). 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 4.5 years. Blood samples will be collected to allow assessment of effect modification by baseline 25-hydroxyvitamin D, omega-3 fatty acid levels, as well as by apolipoprotein E4 status. At 1-year intervals, participants will receive a new supply of pills and a follow-up questionnaire on compliance, possible side effects and medical history. At 1.5 to 2-year intervals, VITAL-cog participants will receive follow-up cognitive function assessments, for a total of 3 assessments over the 4.5 years;participants in the 10th percentile of worst decline will also receive telephone informant interviews using the Dementia Questionnaire. Given our success with prior telephone based cognitive function assessments in multiple trial settings, we believe VITAL-cog will be able to provide definitive results regarding the study hypotheses. To complete pre-randomization assessment of cognitive function, it is critical that VITAL-Cog be undertaken in parallel to the placebo run-in period for the parent trial (1 U01 CA138962), which is scheduled to begin in April 2010. PUBLIC HEALTH RELEVANCE: Given the projected aging of the population, maintaining cognitive function into older ages is of major public health importance, and early interventions may be most effective. The VITAL (VITamin D and OmegA-3 TriaL) study was recently funded and will begin recruitment in January 2010 to investigate the effects of vitamin D and marine omega-3 fatty acid supplements on heart health and cancer prevention. 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.
Funding Period: 2010-08-01 - 2015-05-31
more information: NIH RePORT

Top Publications

  1. 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

Detail Information

Publications1

  1. 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
    ....

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. 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. ..
  3. VITAL-DEP: Depression Endpoint Prevention in the VITamin D and OmegA-3 TriaL
    OLIVIA IFEOMA OKEREKE; Fiscal Year: 2013
    ....
  4. 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. ..
  5. Vitamin D and Fish Oil for Autoimmune Disease, Inflammation and Joint Pain
    Karen H Costenbader; Fiscal Year: 2013
    ....
  6. Hopkins Center for Eliminate Cardiovascular Health Disparities
    Lisa A Cooper; Fiscal Year: 2013
    ..abstract_text> ..
  7. IL-13 and IL-17 dynamics in the asthmatic airway
    Dean Sheppard; Fiscal Year: 2013
    ..RELEVANCE: Epithelial cells line the airways and play an important role in asthma. Micro-RNAs regulate gene expression. We will identify the nature, causes and consequences of changes in airway epithelial cell micro-RNAs in asthma. ..
  8. Effects of Vitamin D and Marine Omega-3 Fatty Acids on Anemia in the Elderly
    Nancy Berliner; Fiscal Year: 2013
    ..abstract_text> ..
  9. 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. ..
  10. Novel Mechanisms of NSAID Action in Alzheimer's Disease
    Edward H Koo; Fiscal Year: 2013
    ..By providing additional preclinical and clinical information on GAMs, such studies should contribute significantly to the further development of GSMs as Alzheimer's therapeutics. ..