Randomized trial of vitamin D and omega-3 fatty acids for diabetic kidney disease

Summary

Principal Investigator: Ian H De Boer
Abstract: DESCRIPTION (provided by applicant): We propose a randomized, placebo-controlled clinical trial of vitamin D3 (cholecalciferol) and omega-3 fatty acids (eicosapentaenoic acid plus docosahexaenoic acid) to prevent the development and progression of diabetic kidney disease (DKD). Persons with diabetes are at high risk of developing kidney disease, and DKD is both the leading cause of end stage renal disease in the developed world and a potent amplifier of cardiovascular disease risk. Vitamin D and omega-3 fatty acids are promising interventions for DKD prevention and treatment, based on results of animal-experimental models and early human studies. Because these interventions are relatively safe, inexpensive, and widely available, they may offer opportunity to substantially reduce the burden of DKD in large populations. We aim to test whether vitamin D3 and/or omega-3 fatty acids prevent progression of albuminuria and loss of glomerular filtration rate, two complementary manifestations of DKD, over 4 years of treatment. To effectively and efficiently test study hypotheses, we propose an ancillary study to the Vitamin D and Omega-3 Trial (VITAL), an NIH-funded randomized clinical trial. In VITAL, 20,000 participants (men ages e 60 years, women ages e 65 years) will be randomly assigned in a 2x2 factorial design to vitamin D3 (cholecalciferol) 1600 IU daily versus placebo, and to eicosapentaenoic acid 500 mg plus docosahexaenoic acid 500 mg daily versus placebo, and followed for a mean of 5 years to assess effects on cardiovascular disease and cancer events. Leveraging the established infrastructure of VITAL, we propose to identify and recruit a sub-cohort of 1,500 VITAL participants with diabetes at baseline and to ascertain effects of study interventions on albuminuria and glomerular filtration rate in this group. Following the simple and cost-efficient design of the parent VITAL trial, biospecimens will be collected locally and delivered to the VITAL central laboratory by mail. First morning voids will be collected at baseline and year 4 for measurement of urine albumin-creatinine ratio. Blood samples will be collected simultaneously for measurement of glomerular filtration rate (using serum creatinine and cystatin C), 25- hydroxyvitamin D, eicosapentaenoic acid plus docosahexaenoic acid, C-reactive protein, and hemoglobin A1c. The proposed studies are designed to determine whether vitamin D3 and/or omega-3 fatty acids have causal and clinically relevant effects on the development and progression of DKD. PUBLIC HEALTH RELEVANCE: Diabetic kidney disease (DKD) is a cause of substantial morbidity and mortality. Despite widespread use of intensive glycemic control and renin-angiotensin-aldosterone system inhibitors, renal and cardiovascular consequences of DKD remain common. This study will evaluate whether vitamin D3 and/or omega-3 fatty acids are safe and effective interventions to reduce the burden of DKD among the large and growing diabetic population.
Funding Period: 2010-09-01 - 2015-08-31
more information: NIH RePORT

Top Publications

  1. pmc Temporal trends in the prevalence of diabetic kidney disease in the United States
    Ian H De Boer
    Kidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA 98104, USA
    JAMA 305:2532-9. 2011
  2. pmc Estimated GFR and circulating 24,25-dihydroxyvitamin D3 concentration: a participant-level analysis of 5 cohort studies and clinical trials
    Ian H De Boer
    Division of Nephrology, Department of Medicine, Seattle, WA Kidney Research Institute, Department of Medicine, Seattle, WA Department of Epidemiology, University of Washington, Seattle, WA Electronic address
    Am J Kidney Dis 64:187-97. 2014
  3. pmc Kidney disease and related findings in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study
    Ian H De Boer
    Corresponding author Ian H de Boer
    Diabetes Care 37:24-30. 2014
  4. pmc Racial differences in the association of serum 25-hydroxyvitamin D concentration with coronary heart disease events
    Cassianne Robinson-Cohen
    Department of Medicine, Kidney Research Institute, University of Washington, Seattle 98104, USA
    JAMA 310:179-88. 2013
  5. pmc Invited commentary: Quantifying salt in urine--a complex solution
    Ian H De Boer
    Am J Epidemiol 177:1193-5; discussion 1196-8. 2013
  6. pmc Estimating mean annual 25-hydroxyvitamin D concentrations from single measurements: the Multi-Ethnic Study of Atherosclerosis
    Michael C Sachs
    Kidney Research Institute and Division of Nephrology, University of Washington, Seattle, WA, USA
    Am J Clin Nutr 97:1243-51. 2013
  7. pmc Circulating vitamin D metabolites and subclinical atherosclerosis in type 1 diabetes
    Michael C Sachs
    University of Washington, Seattle, Washington, USA
    Diabetes Care 36:2423-9. 2013
  8. pmc Impaired vitamin D metabolism in CKD
    Cortney Bosworth
    Division of Nephrology and Kidney Research Institute, University of Washington, Seattle, WA, USA
    Semin Nephrol 33:158-68. 2013
  9. pmc Kidney disease and increased mortality risk in type 2 diabetes
    Maryam Afkarian
    Kidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA 98014, USA
    J Am Soc Nephrol 24:302-8. 2013
  10. pmc Circulating vitamin D metabolites and kidney disease in type 1 diabetes
    Ian H De Boer
    Kidney Research Institute and Division of Nephrology, University of Washington, Box 359606, 325 Ninth Avenue, Seattle, Washington 98104, USA
    J Clin Endocrinol Metab 97:4780-8. 2012

Detail Information

Publications17

  1. pmc Temporal trends in the prevalence of diabetic kidney disease in the United States
    Ian H De Boer
    Kidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA 98104, USA
    JAMA 305:2532-9. 2011
    ..Over time, the prevalence of diabetic kidney disease (DKD) may increase due to the expanding size of the diabetes population or decrease due to the implementation of diabetes therapies...
  2. pmc Estimated GFR and circulating 24,25-dihydroxyvitamin D3 concentration: a participant-level analysis of 5 cohort studies and clinical trials
    Ian H De Boer
    Division of Nephrology, Department of Medicine, Seattle, WA Kidney Research Institute, Department of Medicine, Seattle, WA Department of Epidemiology, University of Washington, Seattle, WA Electronic address
    Am J Kidney Dis 64:187-97. 2014
    ..We tested associations of estimated GFR (eGFR) with the circulating concentration of 24,25-dihydroxyvitamin D3 (24,25[OH]2D3), the most abundant product of 25(OH)D3 catabolism, across populations with a wide range of GFRs...
  3. pmc Kidney disease and related findings in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study
    Ian H De Boer
    Corresponding author Ian H de Boer
    Diabetes Care 37:24-30. 2014
    ..CONCLUSIONS In the DCCT/EDIC, INT resulted in clinically important, durable reductions in the risks of microalbuminuria, macroalbuminuria, impaired GFR, and hypertension. ..
  4. pmc Racial differences in the association of serum 25-hydroxyvitamin D concentration with coronary heart disease events
    Cassianne Robinson-Cohen
    Department of Medicine, Kidney Research Institute, University of Washington, Seattle 98104, USA
    JAMA 310:179-88. 2013
    ..This association has not been rigorously evaluated in other races or ethnicities, in which the distributions of 25(OH)D concentration and possibly other aspects of 25(OH)D metabolism differ...
  5. pmc Invited commentary: Quantifying salt in urine--a complex solution
    Ian H De Boer
    Am J Epidemiol 177:1193-5; discussion 1196-8. 2013
    ..Further work is needed to extend estimation to additional populations and improve individual-level assessment...
  6. pmc Estimating mean annual 25-hydroxyvitamin D concentrations from single measurements: the Multi-Ethnic Study of Atherosclerosis
    Michael C Sachs
    Kidney Research Institute and Division of Nephrology, University of Washington, Seattle, WA, USA
    Am J Clin Nutr 97:1243-51. 2013
    ..Single measurements may misclassify annual exposure, which may lead to bias in research and complicate clinical decision making...
  7. pmc Circulating vitamin D metabolites and subclinical atherosclerosis in type 1 diabetes
    Michael C Sachs
    University of Washington, Seattle, Washington, USA
    Diabetes Care 36:2423-9. 2013
    ..We tested associations of circulating vitamin D metabolite concentrations with subclinical atherosclerosis among 1,193 participants with type 1 diabetes in the DCCT/EDIC study...
  8. pmc Impaired vitamin D metabolism in CKD
    Cortney Bosworth
    Division of Nephrology and Kidney Research Institute, University of Washington, Seattle, WA, USA
    Semin Nephrol 33:158-68. 2013
    ..New insights into the mechanisms and regulation of vitamin D metabolism may lead to novel approaches to assess and treat impaired vitamin D metabolism in chronic kidney disease...
  9. pmc Kidney disease and increased mortality risk in type 2 diabetes
    Maryam Afkarian
    Kidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA 98014, USA
    J Am Soc Nephrol 24:302-8. 2013
    ..2%-29.6%) when further adjusted. We observed similar patterns for cardiovascular and noncardiovascular mortality. In conclusion, those with kidney disease predominantly account for the increased mortality observed in type 2 diabetes...
  10. pmc Circulating vitamin D metabolites and kidney disease in type 1 diabetes
    Ian H De Boer
    Kidney Research Institute and Division of Nephrology, University of Washington, Box 359606, 325 Ninth Avenue, Seattle, Washington 98104, USA
    J Clin Endocrinol Metab 97:4780-8. 2012
    ..Impaired vitamin D metabolism may contribute to the development and progression of diabetic kidney disease...
  11. pmc Serum 25-hydroxyvitamin D concentration and risk for major clinical disease events in a community-based population of older adults: a cohort study
    Ian H De Boer
    University of Washington, Seattle, USA
    Ann Intern Med 156:627-34. 2012
    ..Current clinical 25-(OH)D targets based on associations with intermediate markers of bone metabolism may not reflect optimal levels for other chronic diseases and do not account for known seasonal variation in 25-(OH)D concentration...
  12. 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
    ....
  13. ncbi Renal outcomes in patients with type 1 diabetes and macroalbuminuria
    Ian H De Boer
    Division of Nephrology and Kidney Research Institute and
    J Am Soc Nephrol 25:2342-50. 2014
    ..However, through at least 10 years of follow-up, AER could often be controlled, and GFR frequently remained in the normal range. ..

Research Grants30

  1. 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. ..
  2. VITamin D and omegA-3 triaL (VITAL)
    JOANN ELISABETH MANSON; Fiscal Year: 2013
    ..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. ..
  3. Residual Kidney Function in ESRD: Measurements, Serum Markers and Outcomes
    Tariq Shafi; Fiscal Year: 2013
    ..This research project will develop methods for measuring kidney function in dialysis patients and test if treatment with angiotensin converting enzyme inhibitors can preserve kidney function in dialysis patients. ..
  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. North American Mitochondrial Disease Consortium (NAMDC)
    JOHN L THOMPSON; Fiscal Year: 2013
    ....
  7. Novel serum and urinary biomarkers of diabetic kidney disease
    Steven G Coca; Fiscal Year: 2013
    ....
  8. Vitamin D and Omega-3 Fatty Acids(VITAL Trial): Effects on Fractures
    MERYL SUSAN LEBOFF; Fiscal Year: 2013
    ....
  9. 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. ..
  10. Diabetes Prevention in the Vitamin D and Omega-3 Trial
    Yiqing Song; Fiscal Year: 2013
    ....
  11. Women's Health Study: Continued Follow-up
    I Min Lee; Fiscal Year: 2013
    ..1 ..
  12. 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. ..
  13. Hopkins Center for Eliminate Cardiovascular Health Disparities
    Lisa A Cooper; Fiscal Year: 2013
    ..abstract_text> ..
  14. Vitamin D and Fish Oil for Autoimmune Disease, Inflammation and Joint Pain
    Karen H Costenbader; Fiscal Year: 2013
    ....
  15. Effects of Vitamin D and Marine Omega-3 Fatty Acids on Anemia in the Elderly
    Nancy Berliner; Fiscal Year: 2013
    ..abstract_text> ..
  16. 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. ..
  17. Regulatory Mechanisms In Intestinal Motility
    Kenton M Sanders; Fiscal Year: 2013
    ..The investigative team is highly synergistic and collaborative, and the PPG has a long track-record of productivity and novel discovery ..
  18. 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. ..
  19. Vitamin D and type 2 diabetes (D2d)
    Anastassios G Pittas; Fiscal Year: 2013
    ....
  20. VITAL-DEP: Depression Endpoint Prevention in the VITamin D and OmegA-3 TriaL
    OLIVIA IFEOMA OKEREKE; Fiscal Year: 2013
    ....
  21. Phenotypes of diabetic kidney disease and the relationship to retinal pathology
    Amy Mottl; Fiscal Year: 2013
    ..This will form the basis for an R01 which will extend these robust techniques to a larger cohort and provide definitive data regarding the phenotypes of diabetic complications of the kidney and eye and their relationship to each other. ..
  22. BIOLOGY OF NEUROENDOCRINE PEPTIDES
    Marc R Montminy; Fiscal Year: 2013
    ..Specifying the contributions of the CRF family of ligands and receptors to the maintenance of homeostasis and to stress-linked allostasis may improve our ability to manage diseases, including mood and metabolic disorders ..
  23. A Triple Marker Approach To Optimize CKD Detection Among Black and White Adults
    CARMEN ALICIA PERALTA; Fiscal Year: 2013
    ..The data generated from these projects can directly lead to the evaluation of screening strategies that are targeted to individual risk. ..