Diabetes
Conditions
Keywords
vitamin D3, omega-3 fatty acids, fish oil, diabetes, kidney disease, albuminuria, urine albumin excretion, glomerular filtration rate, diabetic kidney disease
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTVitamin D
Vitamin D3 (cholecalciferol), 2000 IU per day.
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_SUPPLEMENTVitamin D placebo
Vitamin D3 placebo
DIETARY_SUPPLEMENTFish oil placebo
Fish oil placebo
Sponsors
Brigham and Women's Hospital
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Estimated Glomerular Filtration Rate | baseline to 5 years | GFR estimated from serum creatinine and cystatin C |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urine Albumin Excretion | baseline to 5 years | Change in urine albumin-creatinine ratio. |
| Change in C-reactive Protein | baseline to 5 years | Changes in serum concentrations in CRP |
| Change in Interleukin-6 | baseline to 5 years | Changes in serum concentrations in IL-6 |
| Change in NT-proBNP | baseline to 5 years | Changes in serum concentrations in NT-proBNP |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vitamin D + Fish Oil Placebo Vitamin D and fish oil placebo
Vitamin D: Vitamin D3 (cholecalciferol), 2000 IU per day.
Fish oil placebo: Fish oil placebo | 333 |
| Vitamin D Placebo + Fish Oil Vitamin D placebo and omega-3 fatty acids (fish oil)
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 \[DHA\]).
Vitamin D placebo: Vitamin D3 placebo | 289 |
| Vitamin D Placebo + Fish Oil Placebo Vitamin D placebo and fish oil placebo
Vitamin D placebo: Vitamin D3 placebo
Fish oil placebo: Fish oil placebo | 320 |
| Vitamin D + Fish Oil Vitamin D and omega-3 fatty acids (fish oil)
Vitamin D: Vitamin D3 (cholecalciferol), 2000 IU per day.
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 \[DHA\]). | 370 |
| Total | 1,312 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 19 | 21 | 19 | 21 |
| Overall Study | Lost to Follow-up | 78 | 56 | 75 | 89 |
Baseline characteristics
| Characteristic | Vitamin D + Fish Oil Placebo | Vitamin D Placebo + Fish Oil | Vitamin D Placebo + Fish Oil Placebo | Vitamin D + Fish Oil | Total |
|---|---|---|---|---|---|
| Age, Continuous | 67.4 years STANDARD_DEVIATION 6.7 | 68.2 years STANDARD_DEVIATION 6.7 | 67.5 years STANDARD_DEVIATION 6.9 | 67.4 years STANDARD_DEVIATION 7.3 | 67.6 years STANDARD_DEVIATION 6.9 |
| Race/Ethnicity, Customized American Indian/Alaska Natuve | 4 Participants | 1 Participants | 2 Participants | 6 Participants | 13 Participants |
| Race/Ethnicity, Customized Asian/Pacific Islander | 8 Participants | 7 Participants | 7 Participants | 13 Participants | 35 Participants |
| Race/Ethnicity, Customized Hispanic | 21 Participants | 16 Participants | 18 Participants | 20 Participants | 75 Participants |
| Race/Ethnicity, Customized Non-Hispanic black | 75 Participants | 59 Participants | 71 Participants | 73 Participants | 278 Participants |
| Race/Ethnicity, Customized Non-Hispanic white | 211 Participants | 199 Participants | 207 Participants | 240 Participants | 857 Participants |
| Race/Ethnicity, Customized Not available | 6 Participants | 5 Participants | 6 Participants | 9 Participants | 26 Participants |
| Race/Ethnicity, Customized Other | 8 Participants | 2 Participants | 9 Participants | 9 Participants | 28 Participants |
| Sex: Female, Male Female | 143 Participants | 131 Participants | 151 Participants | 184 Participants | 609 Participants |
| Sex: Female, Male Male | 190 Participants | 158 Participants | 169 Participants | 186 Participants | 703 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 19 / 333 | 21 / 289 | 19 / 320 | 21 / 370 |
| other Total, other adverse events | 134 / 333 | 135 / 289 | 133 / 320 | 136 / 370 |
| serious Total, serious adverse events | 45 / 333 | 59 / 289 | 45 / 320 | 44 / 370 |
Outcome results
Primary
Change in Estimated Glomerular Filtration Rate
GFR estimated from serum creatinine and cystatin C
Time frame: baseline to 5 years
Population: Outcomes analyzed according to factorial assignments, without evidence of treatment interaction.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vitamin D | Change in Estimated Glomerular Filtration Rate | -12.3 mL/min/1.73m2 |
| Vitamin D Placebo | Change in Estimated Glomerular Filtration Rate | -13.1 mL/min/1.73m2 |
| Fish Oil | Change in Estimated Glomerular Filtration Rate | -12.2 mL/min/1.73m2 |
| Fish Oil Placebo | Change in Estimated Glomerular Filtration Rate | -13.1 mL/min/1.73m2 |
p-value: 0.2595% CI: [-0.7, 2.5]Mixed Models Analysis
p-value: 0.2795% CI: [-0.7, 2.6]Mixed Models Analysis
Secondary
Change in C-reactive Protein
Changes in serum concentrations in CRP
Time frame: baseline to 5 years
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D | Change in C-reactive Protein | 0.93 mg/L | Standard Deviation 2.71 |
| Vitamin D Placebo | Change in C-reactive Protein | 1.03 mg/L | Standard Deviation 3.03 |
| Fish Oil | Change in C-reactive Protein | 0.90 mg/L | Standard Deviation 2.82 |
| Fish Oil Placebo | Change in C-reactive Protein | 1.05 mg/L | Standard Deviation 2.89 |
Secondary
Change in Interleukin-6
Changes in serum concentrations in IL-6
Time frame: baseline to 5 years
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D | Change in Interleukin-6 | 1.04 pg/ml | Standard Deviation 4.48 |
| Vitamin D Placebo | Change in Interleukin-6 | 1.09 pg/ml | Standard Deviation 4.44 |
| Fish Oil | Change in Interleukin-6 | 1.10 pg/ml | Standard Deviation 4.33 |
| Fish Oil Placebo | Change in Interleukin-6 | 1.02 pg/ml | Standard Deviation 4.6 |
Secondary
Change in NT-proBNP
Changes in serum concentrations in NT-proBNP
Time frame: baseline to 5 years
Population: 2x2 factorial design
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D | Change in NT-proBNP | 1.72 ng/l | Standard Deviation 3.24 |
| Vitamin D Placebo | Change in NT-proBNP | 1.38 ng/l | Standard Deviation 3.02 |
| Fish Oil | Change in NT-proBNP | 1.56 ng/l | Standard Deviation 3.07 |
| Fish Oil Placebo | Change in NT-proBNP | 1.54 ng/l | Standard Deviation 3.24 |
Secondary
Change in Urine Albumin Excretion
Change in urine albumin-creatinine ratio.
Time frame: baseline to 5 years
Population: Outcomes analyzed according to factorial assignments, without evidence of treatment interaction.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Vitamin D | Change in Urine Albumin Excretion | 2.97 geometric mean ratio |
| Vitamin D Placebo | Change in Urine Albumin Excretion | 3.02 geometric mean ratio |
| Fish Oil | Change in Urine Albumin Excretion | 2.94 geometric mean ratio |
| Fish Oil Placebo | Change in Urine Albumin Excretion | 3.05 geometric mean ratio |
p-value: 0.995% CI: [0.84, 1.17]Mixed Models Analysis
p-value: 0.6495% CI: [0.81, 1.14]Mixed Models Analysis