Vitamin D and Omega-3 Trial to Prevent and Treat Diabetic Kidney Disease

Study Overview
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Brief Summary
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The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is a randomized clinical trial in 20,000 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 participants in VITAL with a history of diabetes and will examine whether vitamin D or fish oil prevents the development and progression of diabetic kidney disease.

Detailed Description
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This ancillary study to the VITamin D and OmegA-3 TriaL (VITAL) will test whether vitamin D3, omega-3 fatty acids, or both prevent the development and progression of diabetic kidney disease (DKD). Persons with diabetes are at high risk of kidney disease. In 2005-2008, the prevalence of DKD among people with type 2 diabetes in the United States was 34.5%. Moreover, from 1988-1994 to 2005-2008, the prevalence of DKD in the United States grew 34% to 6.9 million people. 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. This VITAL ancillary study will 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 3 years of treatment. In VITAL, 20,000 participants will be randomly assigned in a 2x2 factorial design to vitamin D3 (cholecalciferol) 2000 IU daily versus placebo, and to eicosapentaenoic acid 465 mg plus docosahexaenoic acid 375 mg daily versus placebo, and followed for a mean of 5 years to assess effects on cardiovascular disease and cancer events. This ancillary study will identify and recruit a sub-cohort of VITAL participants with diabetes at baseline and ascertain effects of study interventions on albuminuria and glomerular filtration rate in this group. First morning voids will be collected at baseline and year 3 for measurement of urine albumin-creatinine ratio. Blood samples will be collected simultaneously for measurement of estimated glomerular filtration rate (using serum creatinine and cystatin C) and other relevant biomarkers. This VITAL ancillary study is 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.

Official Title
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Vitamin D and Omega-3 Trial to Prevent and Treat Diabetic Kidney Disease

Conditions
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Diabetes

Intervention / Treatment
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* Dietary Supplement: Vitamin D
* Drug: Omega-3 fatty acids (fish oil)
* Dietary Supplement: Vitamin D placebo
* Dietary Supplement: Fish oil placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants in VITAL (NCT 01169259) with a self-reported physician diagnosis of diabetes are eligible to participate in this ancillary study. Exclusion Criteria: Type 1 diabetes Diabetes only during pregnancy Known cause of kidney disease other than diabetes History of kidney transplantation

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin D + fish oil<br>Vitamin D and omega-3 fatty acids (fish oil) | Dietary Supplement: Vitamin D<br>* Vitamin D3 (cholecalciferol), 2000 IU per day.<br>Drug: Omega-3 fatty acids (fish oil)<br>* 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]).<br>|
| Active Comparator: Vitamin D + fish oil placebo<br>Vitamin D and fish oil placebo | Dietary Supplement: Vitamin D<br>* Vitamin D3 (cholecalciferol), 2000 IU per day.<br>Dietary Supplement: Fish oil placebo<br>* Fish oil placebo<br>|
| Active Comparator: Vitamin D placebo + fish oil<br>Vitamin D placebo and omega-3 fatty acids (fish oil) | Drug: Omega-3 fatty acids (fish oil)<br>* 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]).<br>Dietary Supplement: Vitamin D placebo<br>* Vitamin D3 placebo<br>|
| Placebo Comparator: Vitamin D placebo + fish oil placebo<br>Vitamin D placebo and fish oil placebo | Dietary Supplement: Vitamin D placebo<br>* Vitamin D3 placebo<br>Dietary Supplement: Fish oil placebo<br>* Fish oil placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Estimated Glomerular Filtration Rate | GFR estimated from serum creatinine and cystatin C | baseline to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Urine Albumin Excretion | Change in urine albumin-creatinine ratio. | baseline to 5 years | 
| Change in C-reactive Protein | Changes in serum concentrations in CRP | baseline to 5 years | 
| Change in Interleukin-6 | Changes in serum concentrations in IL-6 | baseline to 5 years | 
| Change in NT-proBNP | Changes in serum concentrations in NT-proBNP | baseline to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin D3, omega-3 fatty acids, fish oil, diabetes, kidney disease, albuminuria, urine albumin excretion, glomerular filtration rate, diabetic kidney disease