Kidney Transplantation, Vitamin D Deficiency
Conditions
Keywords
Kidney transplantation (KTX), Vitamin D deficiency, Cardiovascular Disease (CVD), Vascular risk, Parathyroid hormone (PTH), Carotid intima media thickness (CIMT), Insulin resistance (IR)
Brief summary
Vitamin D deficiency accelerates vascular risk progression after kidney transplant.
Detailed description
This trial will assess the following aims: 1. Time to plateau vitamin D concentrations after initiating vitamin D supplements 2. Safety of vitamin D replacement based on serum and urine calcium 3. Effect of vitamin D on PTH concentration in individuals with elevated parathyroid hormone 4. Effect of vitamin D on markers of insulin resistance and inflammation
Interventions
DIETARY_SUPPLEMENTStandard vitamin D3 treatment
10,000 I.U./wk of vitamin D3 orally for 6 months
DIETARY_SUPPLEMENTHigh dose vitamin D3 treatment
50,000 I.U./wk of vitamin D3 orally for 6 months
Sponsors
University of Nebraska
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Kidney transplant more than 6 months ago * 19 years or older * 25-hydroxy vitamin D ≤35 ng/ml
Exclusion criteria
* Estimated Glomerular filtration rate (GFR) \<30 ml/min/1.73m² * Previous small bowel or lung transplant * Pancreas transplant less than 6 months ago * Cancer or any condition that would change their weight dramatically in the near future such as malabsorption * Willing to return for testing every two months * Women who are pregnant or \< 6 weeks postpartum * Calcium \> 10.5 mg/dl * Phosphate \> 4.8 mg/dl * Drinking more than 2 alcohol drinks a day or 14 drinks per week * History of parathyroid surgery * Known granulomatous disease * Taking any seizure medication that affects vitamin D * Taking Zemplar ® and/or Rocaltrol ® * History of kidney stones in the past 20 years * Not on a stable dose of bisphosphonate for the past three months * Planning on a pancreas transplant within the next year * In any other research study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Compare Efficacy and Safety of Two Vitamin D Supplements of These Doses in Normalizing Vitamin D Concentrations. | Baseline and 6 months | The 6 month change (6 month - Baseline) was compared between the two treatment arms of vitamin D supplements for normalizing vitamin D concentrations. Higher change values indicate improvement in vitamin D levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Ability of Vitamin D to Reduce Parathyroid Hormone Concentration. | baseline and 6 months | The 6 month change (6 month - Baseline) in parathyroid hormone concentration was compared between the two treatment arms. |
| The Ability of Vitamin D to Alter Spot Urine Protein-Creatinine Ratio. | 6 months | The 6 month change (6 month - Baseline) in spot urine protein-creatinine ratio was compared between the two treatment arms. |
| The Effect of Vitamin D Supplementation on 6 Month High-sensitivity C-reactive Protein (HsCRP) Levels. | Baseline and 6 months | The 6 month change in High-sensitivity C-reactive protein (HsCRP) levels was compared between the two treatment arms. |
| The Effect of Vitamin D Supplementation on Insulin Resistance at 6 Months | Baseline and 6 months | The 6 month change (6 month - Baseline) in insulin resistance was assessed with HOMA-IR (Homeostatic Model Assessment-Insulin Resistance), which is calculated by fasting glucose (mg/dL) X fasting insulin (mU/L) /405. |
Countries
United States
Participant flow
Pre-assignment details
165 subjects were screened, and 93 subjects were eligible and were randomized to treatments. Three patients voluntarily withdrew consent immediately following randomization. A total of 90 subjects received treatments.
Participants by arm
| Arm | Count |
|---|---|
| Standard Vitamin Treatment Standard vitamin treatment
vitamin D3: 10,000 I.U./wk of vitamin D3 orally for 6 months | 46 |
| 50,000 I.U. of Vitamin D3 50,000 I.U. of vitamin D3
vitamin D3: 50,000 I.U./wk of vitamin D3 orally for 6 months | 44 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Standard Vitamin Treatment | Total | 50,000 I.U. of Vitamin D3 |
|---|---|---|---|
| Age, Continuous | 55.3 years STANDARD_DEVIATION 10.5 | 53.8 years STANDARD_DEVIATION 11.4 | 52.1 years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 6 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 83 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 12 Participants | 7 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 | 40 Participants | 77 Participants | 37 Participants |
| Sex: Female, Male Female | 27 Participants | 48 Participants | 21 Participants |
| Sex: Female, Male Male | 19 Participants | 42 Participants | 23 Participants |
| Vitamin D Concentration | 27.2 ng/ml STANDARD_DEVIATION 5.3 | 26.7 ng/ml STANDARD_DEVIATION 6.1 | 26.3 ng/ml STANDARD_DEVIATION 6.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 46 | 2 / 44 |
| serious Total, serious adverse events | 0 / 46 | 1 / 44 |
Outcome results
Primary
Compare Efficacy and Safety of Two Vitamin D Supplements of These Doses in Normalizing Vitamin D Concentrations.
The 6 month change (6 month - Baseline) was compared between the two treatment arms of vitamin D supplements for normalizing vitamin D concentrations. Higher change values indicate improvement in vitamin D levels.
Time frame: Baseline and 6 months
Population: Patients who had baseline and 6 month 25-hydroxy Vitamin D levels measured
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Vitamin Treatment | Compare Efficacy and Safety of Two Vitamin D Supplements of These Doses in Normalizing Vitamin D Concentrations. | 8 ng/ml |
| 50,000 I.U. of Vitamin D3 | Compare Efficacy and Safety of Two Vitamin D Supplements of These Doses in Normalizing Vitamin D Concentrations. | 29 ng/ml |
Secondary
The Ability of Vitamin D to Alter Spot Urine Protein-Creatinine Ratio.
The 6 month change (6 month - Baseline) in spot urine protein-creatinine ratio was compared between the two treatment arms.
Time frame: 6 months
Population: Available data from patients who had baseline and 6 month spot urine protein-creatinine ratio levels obtained.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Vitamin Treatment | The Ability of Vitamin D to Alter Spot Urine Protein-Creatinine Ratio. | -0.45 mg/mmol |
| 50,000 I.U. of Vitamin D3 | The Ability of Vitamin D to Alter Spot Urine Protein-Creatinine Ratio. | -1.95 mg/mmol |
Secondary
The Ability of Vitamin D to Reduce Parathyroid Hormone Concentration.
The 6 month change (6 month - Baseline) in parathyroid hormone concentration was compared between the two treatment arms.
Time frame: baseline and 6 months
Population: Available data from patients who had baseline and 6 month parathyroid hormone concentration levels obtained.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Vitamin Treatment | The Ability of Vitamin D to Reduce Parathyroid Hormone Concentration. | 1.0 pg/ml |
| 50,000 I.U. of Vitamin D3 | The Ability of Vitamin D to Reduce Parathyroid Hormone Concentration. | -9.0 pg/ml |
Secondary
The Effect of Vitamin D Supplementation on 6 Month High-sensitivity C-reactive Protein (HsCRP) Levels.
The 6 month change in High-sensitivity C-reactive protein (HsCRP) levels was compared between the two treatment arms.
Time frame: Baseline and 6 months
Population: Available data from patients who had baseline and 6 month HsCRP levels obtained
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Vitamin Treatment | The Effect of Vitamin D Supplementation on 6 Month High-sensitivity C-reactive Protein (HsCRP) Levels. | 0.3 mg/dl |
| 50,000 I.U. of Vitamin D3 | The Effect of Vitamin D Supplementation on 6 Month High-sensitivity C-reactive Protein (HsCRP) Levels. | 0.15 mg/dl |
Secondary
The Effect of Vitamin D Supplementation on Insulin Resistance at 6 Months
The 6 month change (6 month - Baseline) in insulin resistance was assessed with HOMA-IR (Homeostatic Model Assessment-Insulin Resistance), which is calculated by fasting glucose (mg/dL) X fasting insulin (mU/L) /405.
Time frame: Baseline and 6 months
Population: Available data from patients who had baseline and 6 month HOMA-IR levels obtained.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Vitamin Treatment | The Effect of Vitamin D Supplementation on Insulin Resistance at 6 Months | -0.6 (microU/L) x (nmol/L) |
| 50,000 I.U. of Vitamin D3 | The Effect of Vitamin D Supplementation on Insulin Resistance at 6 Months | 0.1 (microU/L) x (nmol/L) |