Characteristics That Modify the Response to Cholecalciferol Treatment
Conditions
Keywords
Vitamin D, cardiovascular disease, MESA, genetics, pharmacogenetics, blood pressure, biomarkers
Brief summary
The goal of this clinical trial is to determine individual-level genetic and metabolic characteristics that modify the response to cholecalciferol treatment. This study is double blind, parallel design, randomized clinical trial that will assess genetic and metabolic characteristics that modify the response to cholecalciferol treatment. . Eligible participants will be randomly assigned to receive cholecalciferol treatment (2,000 international units of cholecalciferol daily by mouth) or placebo in a 3:1 ratio for a total duration of 16-weeks. The planned sample size is 1,600. The primary aim of this study is to identify genetic polymorphisms, clinical characteristics, and biomarkers that modify the biologic response to vitamin D3 treatment, assessed by changes in serum concentrations of parathyroid hormone (PTH) and 1,25(OH)2D and urine calcium excretion.
Interventions
DIETARY_SUPPLEMENTVitamin D3
cholecalciferol (vitamin D3) 2000 IU capsules daily
DRUGPlacebo
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1,600 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) study who are returning for their scheduled 6th MESA study visit. Participants will be recruited from four field centers: Wake Forest University, Winston-Salem, NC; Columbia University, New York, NY; Northwestern University, Evanston, IL; and Johns Hopkins University, Baltimore, MD.
Exclusion criteria
1. Current use of \>1,000 international units (IU) of cholecalciferol daily 2. Current use of any activated vitamin D product (calcitriol, paricalcitol, hectorol) 3. Known history of allergy or adverse reaction to vitamin D treatment 4. Known clinical history of primary hyperparathyroidism 5. Known clinical history of kidney stones within the previous 5 years 6. Current participation in another interventional study 7. Inability to provide written informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Serum 1,25(OH)2D Concentration | 16 weeks |
| Change in Serum PTH Concentration | 16 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Systolic Blood Pressure | 16 weeks | — |
| Change in Urine Calcium Excretion | 16 weeks | Urine calcium excretion estimated as spot urine calcium-creatinine ratio |
| Change in Serum Calcium Concentrations | 16 weeks | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Treatment Vitamin D3: cholecalciferol (vitamin D3) 2000 IU capsules daily | 499 |
| Placebo Placebo | 167 |
| Total | 666 |
Baseline characteristics
| Characteristic | Placebo | Total | Active Treatment |
|---|---|---|---|
| Age, Continuous | 72 years STANDARD_DEVIATION 8 | 72 years STANDARD_DEVIATION 8 | 72 years STANDARD_DEVIATION 8 |
| Race/Ethnicity, Customized Chinese | 19 Participants | 83 Participants | 64 Participants |
| Race/Ethnicity, Customized Hispanic | 29 Participants | 111 Participants | 82 Participants |
| Race/Ethnicity, Customized Non-Hispanic Black | 61 Participants | 245 Participants | 184 Participants |
| Race/Ethnicity, Customized Non-Hispanic White | 58 Participants | 227 Participants | 169 Participants |
| Sex: Female, Male Female | 81 Participants | 353 Participants | 272 Participants |
| Sex: Female, Male Male | 86 Participants | 313 Participants | 227 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 499 | 0 / 167 |
| other Total, other adverse events | 55 / 499 | 16 / 167 |
| serious Total, serious adverse events | 2 / 499 | 2 / 167 |
Outcome results
Primary
Change in Serum 1,25(OH)2D Concentration
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Treatment | Change in Serum 1,25(OH)2D Concentration | 2 pg/mL | Standard Deviation 16 |
| Placebo | Change in Serum 1,25(OH)2D Concentration | -1 pg/mL | Standard Deviation 17 |
Primary
Change in Serum PTH Concentration
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Treatment | Change in Serum PTH Concentration | -3 pg/mL | Standard Deviation 16 |
| Placebo | Change in Serum PTH Concentration | 2 pg/mL | Standard Deviation 18 |
Secondary
Change in Serum Calcium Concentrations
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Treatment | Change in Serum Calcium Concentrations | 0 mg/dL | Standard Deviation 0.3 |
| Placebo | Change in Serum Calcium Concentrations | 0 mg/dL | Standard Deviation 0.3 |
Secondary
Change in Systolic Blood Pressure
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Treatment | Change in Systolic Blood Pressure | -3 mmHg | Standard Deviation 18 |
| Placebo | Change in Systolic Blood Pressure | -4 mmHg | Standard Deviation 16 |
Secondary
Change in Urine Calcium Excretion
Urine calcium excretion estimated as spot urine calcium-creatinine ratio
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Treatment | Change in Urine Calcium Excretion | 8 mg per g of creatinine | Standard Deviation 83 |
| Placebo | Change in Urine Calcium Excretion | 1 mg per g of creatinine | Standard Deviation 70 |