Chronic Kidney Disease, Diabetes Mellitus, Diabetic Kidney Disease
Conditions
Keywords
Diabetes mellitus, Type 2 diabetes, Chronic kidney disease, Diabetic kidney disease, Microalbuminuria, Albuminuria, Vitamin D, Cholecalciferol, Kidney, Renal, Cardiovascular, Clinical trial, Placebo
Brief summary
This study will assess the effects of vitamin D3 supplementation (cholecalciferol; 2000 IU daily) on serum calcium levels, circulating vitamin D levels, and markers of kidney disease and cardiovascular risk among people with diabetes mellitus and early kidney disease. Eligibility criteria include type 2 diabetes and stage 1-2 chronic kidney disease, defined by a urine albumin-creatinine ratio 30-300 mg/g and an estimated glomerular filtration rate ≥ 60 mL/min. Participants will be randomly assigned to treatment with vitamin D3 or placebo, each taken by mouth once daily for a study duration of one year. Study medications will be added to standard treatment, including an angiotensin converting enzyme inhibitor and/or angiotensin II receptor blocker. We hypothesize that vitamin D3, compared with placebo: (1) is well-tolerated and safe among people with diabetes and kidney disease; (2) results in adequate attained circulating vitamin D levels; and (3) positively affects markers of kidney disease and cardiovascular risk.
Interventions
DIETARY_SUPPLEMENTCholecalciferol
2000 IU by mouth daily for one year
DIETARY_SUPPLEMENTPlacebo
One softgel daily for one year
Sponsors
University of Washington Institute for Translational Health Science (KL2)
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of type 2 diabetes mellitus * Urine albumin-creatinine ratio 30-1000 mg/g * Estimated glomerular filtration rate greater than or equal to 60 mL/min * Treatment with angiotensin converting enzyme inhibitor and/or angiotensin II receptor blocker for greater than or equal to 6 months, with a stable dose for greater than or equal to 3 months * Blood pressure less than 140/90 (assessed while taking medications) * Hemoglobin A1c less than 9% (assessed while taking medications) * 25-hydroxyvitamin D less than 30 ng/mL
Exclusion criteria
* Prior dialysis or kidney transplantation * Known cause of albuminuria other than diabetes * Planning to leave the area within 12 months * Life expectancy less than 12 months * Participation in another clinical trial within 6 months * Osteoporosis or other established indication for vitamin D therapy * Vitamin D3 supplement intake greater than 400 IU/day at screening visit * History of nephrolithiasis * Serum calcium greater than 10.2 mg/dL * Dementia, not fluent in English, or unable to provide informed consent without proxy respondent * Incontinent of urine * Failure to take greater than or equal to 80% of placebo pills during study run-in
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urine Albumin Excretion | Baseline, 3 months, and one year | Albumin and creatinine concentrations were measured in 24hr urine collections at baseline, 3 months after randomization, and one year after randomization. We analyzed the difference in log-transformed albumin-creatinine ratio (ACR, mg/g) after randomization (3 months and one year, analyzed together with all available data included) compared with baseline, by treatment assignment. Results are transformed to present percent difference in urine ACR. |
Countries
United States
Participant flow
Recruitment details
Ninety-three participants from medical clinics associated from the University of Washington (Seattle, WA) provided informed consent for this study between February, 2008 through June, 2009.
Pre-assignment details
Of the 93 participants who provided informed consent, 63 were ineligible, 8 withdrew prior to randomization, and 22 were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Cholecalciferol 2000 IU by mouth daily for one year | 11 |
| Placebo One softgel daily for one year | 11 |
| Total | 22 |
Baseline characteristics
| Characteristic | Cholecalciferol | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 4 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 7 Participants | 14 Participants |
| Age, Continuous | 60 years STANDARD_DEVIATION 10 | 61 years STANDARD_DEVIATION 13 | 60 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 10 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 7 Participants | 16 Participants |
| Region of Enrollment United States | 11 participants | 11 participants | 22 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 11 | 10 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
Change in Urine Albumin Excretion
Albumin and creatinine concentrations were measured in 24hr urine collections at baseline, 3 months after randomization, and one year after randomization. We analyzed the difference in log-transformed albumin-creatinine ratio (ACR, mg/g) after randomization (3 months and one year, analyzed together with all available data included) compared with baseline, by treatment assignment. Results are transformed to present percent difference in urine ACR.
Time frame: Baseline, 3 months, and one year
Population: All participants were analyzed
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cholecalciferol | Change in Urine Albumin Excretion | -21 percent difference |
| Placebo | Change in Urine Albumin Excretion | -5 percent difference |
95% CI: [-56, 251]Regression, Linear