Blood Pressure, Endothelial Function, Obesity, Overweight, Renal Function
Conditions
Keywords
renin angiotensin system, vitamin D, uric acid, allopurinol, probenecid, endothelial function
Brief summary
The investigators hypothesize that, among non-hypertensive overweight and obese individuals, treatment of vitamin D deficiency and lowering uric acid concentrations (by either xanthine oxidase inhibition or increased renal excretion) will attenuate renin angiotensin system (RAS) activation, improve endothelial function, and lower blood pressure.
Detailed description
We have demonstrated that lower levels of 25-hydroxyvitamin D (25\[OH\]D) and higher concentrations of uric acid are both potentially modifiable factors that are independently associated with an increased risk of developing hypertension (high blood pressure) in humans. Other investigators have shown that vitamin D supplementation, or lowering uric acid with allopurinol, may reduce blood pressure. Animal experiments suggest that activation of both the systemic and local kidney-specific renin angiotensin systems (RAS) may be the principal mechanism linking 25(OH)D and uric acid with hypertension. In human parallels to these animal studies, we have shown in cross-sectional analyses that non-hypertensive individuals with lower 25(OH)D and higher uric acid levels have increased activation of their systemic and kidney-specific RAS, independent of other factors. However, whether vitamin D supplementation or uric acid lowering attenuates RAS activation has never been demonstrated in humans. Both lower 25(OH)D and higher uric acid concentrations are also associated with endothelial dysfunction in humans, and endothelial function may modulate the RAS and provide an alternate mechanism for the development of hypertension. It remains unclear, however, whether an intervention to increase 25(OH)D or decrease uric acid levels among non-hypertensive adults improves endothelial function; furthermore, it is unknown whether treatment of these individuals would lower blood pressure. Determining whether treatment of 25(OH)D and uric acid concentrations, per se, can attenuate RAS activation, improve endothelial function, and lower blood pressure among nonhypertensive individuals is critically important, with implications stretching beyond hypertension prevention, since RAS activation, endothelial dysfunction, and blood pressure are also implicated in the pathology of cardiovascular and chronic kidney disease. Individuals who are overweight and obese (two-thirds of US adults) represent an important population who are known to have lower 25(OH)D levels, higher uric acid concentrations, activation of the RAS, endothelial dysfunction, and an increased risk of hypertension, cardiovascular disease, and chronic kidney disease. Interestingly, our preliminary data demonstrate that among overweight and obese individuals with normal 25(OH)D or low uric acid levels, adiposity is no longer associated with activation of the RAS, suggesting that low 25(OH)D and high uric acid concentrations might be mediators of the adverse consequences of overweight and obesity.
Interventions
DRUGVitamin D ergocalciferol
50,000 unit soft gel capsule once per week for 8 weeks
DRUGProbenecid
500 mg tablet once per day for 4 weeks, then either 500 mg tablet once per day for 4 weeks or 1000 mg once per day for 4 weeks (8 weeks total)
DRUGAllopurinol
300 mg tablet once per day for 4 weeks then either 300 mg once per day or 600 mg once per day for 4 weeks (8 weeks total)
DRUGPlacebo
Placebo soft gel once per week for 8 weeks
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* 25(OH)D \< 20 ng/mL OR Uric acid ≥ 5 mg/dL * Age ≥ 18, ≤ 75 years * Body Mass Index (BMI) ≥ 25 kg/m\^2
Exclusion criteria
* Hypertension, or on BP-lowering medicine * Diabetes * Coronary Heart Disease * estimated glomerular filtration rate (EGFR) \<60 mL/min * Kidney stones * Active cancer (except non-melanoma skin cancer) * Pregnant * Taking vitamin D supplements and unwilling to stop * Osteoporosis * Hypo- or hypercalcemia * Hypo- or hyperphosphatemia * Known allergy to angiotensin-converting enzyme (ACE)-inhibitors * Taking medication for hyperuricemia * Gout, anemia, cirrhosis, active/chronic hepatitis, abnormal aspartate aminotransferase (AST), alanine aminotransferase (ALT) or total bilirubin levels, or anemia * Known allergy to either allopurinol or probenecid * Current use of didanosine, azothioprine, methotrexate, ketoprofen, ketorolac, mycophenolate, or ACE-inhibitors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Angiotensin II (ATII) Concentration [Uric Acid] | Week 8 | ATII concentration is a measure of systemic renin angiotensin system (RAS) activation. Blood was collected and plasma ATII was analyzed using a double-antibody radioimmunoassay (RIA) laboratory test. |
| Angiotensin II (ATII) Concentration [Vitamin D] | Week 8 | ATII concentration is a measure of systemic renin angiotensin system (RAS) activation. Blood was collected and plasma ATII was analyzed using a double-antibody radioimmunoassay (RIA) laboratory test. |
| Change in Renal Plasma Flow (RPF) Response to Captopril in High Sodium Balance [Uric Acid] | Week 8 (pre and post captopril) | RPF in response to captopril iis a measure of the vasodilator effect from inhibiting angiotensin II (AngII)- mediated vascular tone and therefore the degree of kidney specific Renin Angiotensin System (RAS) activity. Participants consumed a high sodium diet 3 days prior to the test. Following an 8 hour fast, participants remained in a supine (lying down) position and had an intravenous (IV) catheter inserted in each arm, one for infusion and one for blood collection. An 8 milligrams (mg)/kilogram(kg) loading dose of para-aminohippuric acid (PAH) was given, immediately followed by a continuous PAH infusion at 12 mg/minute. After 60 minutes a single dose of 25 mg of captopril was administered. Three pre-captopril measurements and three post-captopril measurements of RPF were made. RPF was normalized to body surface area of 1.73 meters squared (m\^2). The change in RPF was calculated as post-captopril RPF- pre-captopril RPF. |
| Plasma Renin Activity (PRA) [Uric Acid] | Week 8 | PRA is a measure of systemic renin angiotensin system (RAS) activation. Blood was collected and plasma PRA was analyzed using a competitive binding radioimmunoassay (RIA) laboratory test. |
| Change in Renal Plasma Flow (RPF) in Response to Captopril in High Sodium Balance [Vitamin D] | Week 8 (pre and post captopril) | Change in RPF in response to captopril is a measure of the vasodilator effect from inhibiting angiotensin II (AngII)- mediated vascular tone and therefore the degree of kidney specific Renin Angiotensin System (RAS) activity. Participants consumed a high sodium diet 3 days prior to the test. Following an 8 hour fast, participants remained in a supine (lying down) position and had an intravenous (IV) catheter inserted in each arm, one for infusion and one for blood collection. An 8 milligrams (mg)/kilogram(kg) loading dose of para-aminohippuric acid (PAH) was given, immediately followed by a continuous PAH infusion at 12 mg/minute. After 60 minutes a single dose of 25 mg of captopril was administered. Three pre-captopril measurements and three post-captopril measurements of RPF were made. RPF was normalized to body surface area of 1.73 meters squared (m\^2). The change in RPF was calculated as post-captopril RPF- pre-captopril RPF. |
| Plasma Renin Activity (PRA) [Vitamin D] | Week 8 | PRA is a measure of systemic renin angiotensin system (RAS) activation. Blood was collected and plasma PRA was analyzed using a competitive binding radioimmunoassay (RIA) laboratory test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean 24-Hour Ambulatory Blood Pressure (ABP) | Baseline and Week 8 | A 24-hour mean ambulatory blood pressure was monitored using a 24 hour ABP device. The ABP device is a small box that is worn on the belt or pant/skirt line with a line that connect under the clothing to the cuff on the upper arm. Blood Pressure was recorded every 30 minutes during the day and every 60 minutes during the night for 24 hours. |
| Mean 24-Hour Ambulatory Blood Pressure (ABP) Nocturnal Dipping | Baseline and Week 8 | A 24-hour mean ambulatory blood pressure was monitored using a 24 hour ABP device. The ABP device is a small box that is worn on the belt or pant/skirt line with a line that connect under the clothing to the cuff on the upper arm. Blood Pressure was recorded every 30 minutes during the day and every 60 minutes during the night for 24 hours. Nocturnal dipping is the percent change lower between the daytime and nighttime values. |
| Change in Endothelium-Dependent Vasodilation (EDV) | Baseline and Week 8 (pre and post ischaemic stimulus) | Endothelial function was assessed by EDV using brachial artery ultrasonography. Measurements of brachial artery diameter were made under basal conditions and reactive hyperemia following ischaemic stimulus. A blood pressure cuff on the forearm was pumped up for 5 minutes then released. Images were taken at baseline and after reactive hyperemia (increased blood flow). The maximum diameter was determined by the investigator. Change in EDV was expressed as a percent of brachial luminal diameter calculated as post-ischaemic brachial artery diameter - pre-ischaemic brachial artery diameter/pre-ischaemic brachial artery diameter \* 100. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vitamin D Vitamin D ergocalciferol 50,000 unit soft gel capsule once per week for 8 weeks. | 46 |
| Placebo- Vitamin D Placebo soft gel once per week for 8 weeks. | 47 |
| Probenecid Probenecid 500 mg tablet once per day for 4 weeks, then either 500 mg tablet once per day for 4 weeks or 1000 mg once per day for 4 weeks (8 weeks total). | 47 |
| Allopurinol Allopurinol 300 mg tablet once per day for 4 weeks then either 300 mg once per day or 600 mg once per day for 4 weeks (8 weeks total). | 49 |
| Placebo- Uric Acid Placebo tablet once per day for 4 weeks then twice per day for 4 weeks (eight weeks total). | 53 |
| Total | 242 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 3 | 6 | 0 |
| Overall Study | Did not Receive Intervention | 3 | 2 | 1 | 1 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 1 | 3 |
| Overall Study | Non-compliant with Medication | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Not Available for the 8 Week Visit | 0 | 3 | 0 | 0 | 0 |
| Overall Study | Not Compliant with Study Procedures | 0 | 0 | 0 | 4 | 0 |
| Overall Study | Participant Developed a Rash | 0 | 0 | 2 | 1 | 1 |
| Overall Study | Pregnancy | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Started an Exclusionary Medication | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrew due to Health Condition | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Vitamin D | Placebo- Vitamin D | Total | Probenecid | Allopurinol | Placebo- Uric Acid |
|---|---|---|---|---|---|---|
| Age, Continuous | 39 years STANDARD_DEVIATION 13 | 35 years STANDARD_DEVIATION 11 | 41 years STANDARD_DEVIATION 14 | 37 years STANDARD_DEVIATION 14 | 43 years STANDARD_DEVIATION 12.5 | 41 years STANDARD_DEVIATION 14 |
| Angiotensin II Concentration (ATII) [Uric Acid] | — | — | 19.1 pg/mL STANDARD_DEVIATION 4.6 | 19.6 pg/mL STANDARD_DEVIATION 5 | 18.9 pg/mL STANDARD_DEVIATION 4 | 18.8 pg/mL STANDARD_DEVIATION 4.8 |
| Angiotensin II Concentration (ATII) [Vitamin D] | 19.9 picogram(pg)/mL STANDARD_DEVIATION 5.9 | 19.9 picogram(pg)/mL STANDARD_DEVIATION 4.5 | 19.9 picogram(pg)/mL STANDARD_DEVIATION 5 | — | — | — |
| Change in Renal Plasma Flow (RPF) in Response to Captopril [Vitamin D] | 33.9 milliliters(mL)/minute(min) per 1.73 m^2 STANDARD_DEVIATION 56.1 | 37.3 milliliters(mL)/minute(min) per 1.73 m^2 STANDARD_DEVIATION 46.9 | 35.6 milliliters(mL)/minute(min) per 1.73 m^2 STANDARD_DEVIATION 50 | — | — | — |
| Change in RPF in Response to Captopril [Uric Acid] | — | — | 36.3 mL/min per 1.73 m^2 STANDARD_DEVIATION 38.7 | 38 mL/min per 1.73 m^2 STANDARD_DEVIATION 46 | 41 mL/min per 1.73 m^2 STANDARD_DEVIATION 32.2 | 30 mL/min per 1.73 m^2 STANDARD_DEVIATION 35.5 |
| Plasma Renin Activity (PRA) [Uric Acid] | — | — | 0.27 ng/mL STANDARD_DEVIATION 0.4 | 0.3 ng/mL STANDARD_DEVIATION 0.52 | 0.3 ng/mL STANDARD_DEVIATION 0.33 | 0.2 ng/mL STANDARD_DEVIATION 0.33 |
| Plasma Renin Activity (PRA) [Vitamin D] | 0.34 nanograms (ng)/mL per hour STANDARD_DEVIATION 0.37 | 0.42 nanograms (ng)/mL per hour STANDARD_DEVIATION 0.44 | 0.38 nanograms (ng)/mL per hour STANDARD_DEVIATION 0.4 | — | — | — |
| Sex: Female, Male Female | 31 Participants | 31 Participants | 137 Participants | 23 Participants | 24 Participants | 28 Participants |
| Sex: Female, Male Male | 15 Participants | 16 Participants | 105 Participants | 24 Participants | 25 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 43 | 6 / 45 | 16 / 46 | 36 / 48 | 25 / 51 |
| serious Total, serious adverse events | 0 / 43 | 0 / 45 | 4 / 46 | 6 / 48 | 2 / 51 |
Outcome results
Primary
Angiotensin II (ATII) Concentration [Uric Acid]
ATII concentration is a measure of systemic renin angiotensin system (RAS) activation. Blood was collected and plasma ATII was analyzed using a double-antibody radioimmunoassay (RIA) laboratory test.
Time frame: Week 8
Population: All randomized enrolled participants with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vitamin D | Angiotensin II (ATII) Concentration [Uric Acid] | 20.3 pg/mL |
| Placebo- Vitamin D | Angiotensin II (ATII) Concentration [Uric Acid] | 21.4 pg/mL |
| Placebo- Uric Acid | Angiotensin II (ATII) Concentration [Uric Acid] | 19.1 pg/mL |
p-value: 0.3Repeated Measures Analysis
p-value: 0.1Repeated Measures Analysis
Primary
Angiotensin II (ATII) Concentration [Vitamin D]
ATII concentration is a measure of systemic renin angiotensin system (RAS) activation. Blood was collected and plasma ATII was analyzed using a double-antibody radioimmunoassay (RIA) laboratory test.
Time frame: Week 8
Population: All randomized enrolled participants included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D | Angiotensin II (ATII) Concentration [Vitamin D] | 19.5 pg/mL | Standard Deviation 4.4 |
| Placebo- Vitamin D | Angiotensin II (ATII) Concentration [Vitamin D] | 19.7 pg/mL | Standard Deviation 7.1 |
Comparison: Week 8p-value: 0.57t-test, 2 sided
Primary
Change in Renal Plasma Flow (RPF) in Response to Captopril in High Sodium Balance [Vitamin D]
Change in RPF in response to captopril is a measure of the vasodilator effect from inhibiting angiotensin II (AngII)- mediated vascular tone and therefore the degree of kidney specific Renin Angiotensin System (RAS) activity. Participants consumed a high sodium diet 3 days prior to the test. Following an 8 hour fast, participants remained in a supine (lying down) position and had an intravenous (IV) catheter inserted in each arm, one for infusion and one for blood collection. An 8 milligrams (mg)/kilogram(kg) loading dose of para-aminohippuric acid (PAH) was given, immediately followed by a continuous PAH infusion at 12 mg/minute. After 60 minutes a single dose of 25 mg of captopril was administered. Three pre-captopril measurements and three post-captopril measurements of RPF were made. RPF was normalized to body surface area of 1.73 meters squared (m\^2). The change in RPF was calculated as post-captopril RPF- pre-captopril RPF.
Time frame: Week 8 (pre and post captopril)
Population: All randomized enrolled participants included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D | Change in Renal Plasma Flow (RPF) in Response to Captopril in High Sodium Balance [Vitamin D] | 35.7 mL/min per 1.73 m^2 | Standard Deviation 47.7 |
| Placebo- Vitamin D | Change in Renal Plasma Flow (RPF) in Response to Captopril in High Sodium Balance [Vitamin D] | 35.9 mL/min per 1.73 m^2 | Standard Deviation 26.2 |
Comparison: Week 8p-value: 0.72Repeated Measures Analysis
Primary
Change in Renal Plasma Flow (RPF) Response to Captopril in High Sodium Balance [Uric Acid]
RPF in response to captopril iis a measure of the vasodilator effect from inhibiting angiotensin II (AngII)- mediated vascular tone and therefore the degree of kidney specific Renin Angiotensin System (RAS) activity. Participants consumed a high sodium diet 3 days prior to the test. Following an 8 hour fast, participants remained in a supine (lying down) position and had an intravenous (IV) catheter inserted in each arm, one for infusion and one for blood collection. An 8 milligrams (mg)/kilogram(kg) loading dose of para-aminohippuric acid (PAH) was given, immediately followed by a continuous PAH infusion at 12 mg/minute. After 60 minutes a single dose of 25 mg of captopril was administered. Three pre-captopril measurements and three post-captopril measurements of RPF were made. RPF was normalized to body surface area of 1.73 meters squared (m\^2). The change in RPF was calculated as post-captopril RPF- pre-captopril RPF.
Time frame: Week 8 (pre and post captopril)
Population: All randomized enrolled participants with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vitamin D | Change in Renal Plasma Flow (RPF) Response to Captopril in High Sodium Balance [Uric Acid] | 33 mL/min per 1.73 m^2 |
| Placebo- Vitamin D | Change in Renal Plasma Flow (RPF) Response to Captopril in High Sodium Balance [Uric Acid] | 36 mL/min per 1.73 m^2 |
| Placebo- Uric Acid | Change in Renal Plasma Flow (RPF) Response to Captopril in High Sodium Balance [Uric Acid] | 30 mL/min per 1.73 m^2 |
p-value: 0.8Repeated Measures Analysis
p-value: 0.6Repeated Measures Analysis
Primary
Plasma Renin Activity (PRA) [Uric Acid]
PRA is a measure of systemic renin angiotensin system (RAS) activation. Blood was collected and plasma PRA was analyzed using a competitive binding radioimmunoassay (RIA) laboratory test.
Time frame: Week 8
Population: All randomized enrolled participants with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vitamin D | Plasma Renin Activity (PRA) [Uric Acid] | 0.4 ng/mL per hour |
| Placebo- Vitamin D | Plasma Renin Activity (PRA) [Uric Acid] | 0.3 ng/mL per hour |
| Placebo- Uric Acid | Plasma Renin Activity (PRA) [Uric Acid] | 0.2 ng/mL per hour |
p-value: 0.6Repeated Measures Analysis
p-value: 0.7Repeated Measures Analysis
Primary
Plasma Renin Activity (PRA) [Vitamin D]
PRA is a measure of systemic renin angiotensin system (RAS) activation. Blood was collected and plasma PRA was analyzed using a competitive binding radioimmunoassay (RIA) laboratory test.
Time frame: Week 8
Population: All randomized enrolled participants included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D | Plasma Renin Activity (PRA) [Vitamin D] | 0.36 ng/mL per hour | Standard Deviation 0.44 |
| Placebo- Vitamin D | Plasma Renin Activity (PRA) [Vitamin D] | 0.44 ng/mL per hour | Standard Deviation 0.8 |
Comparison: Week 8p-value: 0.77t-test, 2 sided
Secondary
Change in Endothelium-Dependent Vasodilation (EDV)
Endothelial function was assessed by EDV using brachial artery ultrasonography. Measurements of brachial artery diameter were made under basal conditions and reactive hyperemia following ischaemic stimulus. A blood pressure cuff on the forearm was pumped up for 5 minutes then released. Images were taken at baseline and after reactive hyperemia (increased blood flow). The maximum diameter was determined by the investigator. Change in EDV was expressed as a percent of brachial luminal diameter calculated as post-ischaemic brachial artery diameter - pre-ischaemic brachial artery diameter/pre-ischaemic brachial artery diameter \* 100.
Time frame: Baseline and Week 8 (pre and post ischaemic stimulus)
Population: All randomized enrolled participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vitamin D | Change in Endothelium-Dependent Vasodilation (EDV) | Baseline | 6.3 percent of brachial luminal diameter | Standard Deviation 3.6 |
| Vitamin D | Change in Endothelium-Dependent Vasodilation (EDV) | Week 8 | 6.1 percent of brachial luminal diameter | Standard Deviation 4.6 |
| Placebo- Vitamin D | Change in Endothelium-Dependent Vasodilation (EDV) | Baseline | 7.9 percent of brachial luminal diameter | Standard Deviation 4.7 |
| Placebo- Vitamin D | Change in Endothelium-Dependent Vasodilation (EDV) | Week 8 | 6.8 percent of brachial luminal diameter | Standard Deviation 4.7 |
| Placebo- Uric Acid | Change in Endothelium-Dependent Vasodilation (EDV) | Baseline | 7.4 percent of brachial luminal diameter | Standard Deviation 5.1 |
| Placebo- Uric Acid | Change in Endothelium-Dependent Vasodilation (EDV) | Week 8 | 8.3 percent of brachial luminal diameter | Standard Deviation 5.1 |
| Allopurinol | Change in Endothelium-Dependent Vasodilation (EDV) | Week 8 | 6.2 percent of brachial luminal diameter | Standard Deviation 4.8 |
| Allopurinol | Change in Endothelium-Dependent Vasodilation (EDV) | Baseline | 7.6 percent of brachial luminal diameter | Standard Deviation 6 |
| Placebo- Uric Acid | Change in Endothelium-Dependent Vasodilation (EDV) | Baseline | 6.5 percent of brachial luminal diameter | Standard Deviation 3.8 |
| Placebo- Uric Acid | Change in Endothelium-Dependent Vasodilation (EDV) | Week 8 | 7.1 percent of brachial luminal diameter | Standard Deviation 4.9 |
Comparison: Week 8p-value: 0.35t-test, 2 sided
Comparison: Week 8p-value: 0.7t-test, 2 sided
Comparison: Week 8p-value: 0.06t-test, 2 sided
Secondary
Mean 24-Hour Ambulatory Blood Pressure (ABP)
A 24-hour mean ambulatory blood pressure was monitored using a 24 hour ABP device. The ABP device is a small box that is worn on the belt or pant/skirt line with a line that connect under the clothing to the cuff on the upper arm. Blood Pressure was recorded every 30 minutes during the day and every 60 minutes during the night for 24 hours.
Time frame: Baseline and Week 8
Population: All randomized enrolled participants with complete 24-hour ABP data available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall SBP, Week 8 | 121.6 mmHg | Standard Deviation 8.3 |
| Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Asleep SBP, Baseline | 113.9 mmHg | Standard Deviation 11 |
| Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Asleep SBP, Week 8 | 114.7 mmHg | Standard Deviation 8.1 |
| Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Awake SBP, Baseline | 122.4 mmHg | Standard Deviation 10.9 |
| Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Awake SBP, Week 8 | 124.2 mmHg | Standard Deviation 9.1 |
| Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall Diastolic Blood Pressure (DBP), Baseline | 71.6 mmHg | Standard Deviation 6.4 |
| Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall DBP, Week 8 | 72.0 mmHg | Standard Deviation 5.6 |
| Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall Systolic Blood Pressure (SBP), Baseline | 120.4 mmHg | Standard Deviation 10.2 |
| Placebo- Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Awake SBP, Week 8 | 127.6 mmHg | Standard Deviation 9.2 |
| Placebo- Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall Diastolic Blood Pressure (DBP), Baseline | 73.7 mmHg | Standard Deviation 5.8 |
| Placebo- Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Asleep SBP, Week 8 | 117.4 mmHg | Standard Deviation 11.4 |
| Placebo- Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall Systolic Blood Pressure (SBP), Baseline | 123.7 mmHg | Standard Deviation 7.6 |
| Placebo- Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Awake SBP, Baseline | 126.4 mmHg | Standard Deviation 7.4 |
| Placebo- Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Asleep SBP, Baseline | 116.5 mmHg | Standard Deviation 8.7 |
| Placebo- Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall SBP, Week 8 | 124.7 mmHg | Standard Deviation 9.6 |
| Placebo- Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall DBP, Week 8 | 74.7 mmHg | Standard Deviation 7.2 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Asleep SBP, Baseline | 119.2 mmHg | Standard Deviation 12.4 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall DBP, Week 8 | 73.8 mmHg | Standard Deviation 6.9 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall Diastolic Blood Pressure (DBP), Baseline | 73.3 mmHg | Standard Deviation 7.8 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Awake SBP, Week 8 | 128.1 mmHg | Standard Deviation 9.3 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Asleep SBP, Week 8 | 116.2 mmHg | Standard Deviation 9.6 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Awake SBP, Baseline | 130.0 mmHg | Standard Deviation 9.2 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall SBP, Week 8 | 125.2 mmHg | Standard Deviation 9.1 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall Systolic Blood Pressure (SBP), Baseline | 126.9 mmHg | Standard Deviation 10.2 |
| Allopurinol | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall SBP, Week 8 | 123.7 mmHg | Standard Deviation 9.4 |
| Allopurinol | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Asleep SBP, Baseline | 117.1 mmHg | Standard Deviation 10 |
| Allopurinol | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall Systolic Blood Pressure (SBP), Baseline | 124.1 mmHg | Standard Deviation 8.8 |
| Allopurinol | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Awake SBP, Week 8 | 125.1 mmHg | Standard Deviation 9.6 |
| Allopurinol | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall Diastolic Blood Pressure (DBP), Baseline | 72.1 mmHg | Standard Deviation 7.1 |
| Allopurinol | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Asleep SBP, Week 8 | 118.6 mmHg | Standard Deviation 11.7 |
| Allopurinol | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall DBP, Week 8 | 72.0 mmHg | Standard Deviation 6.5 |
| Allopurinol | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Awake SBP, Baseline | 126.7 mmHg | Standard Deviation 8.4 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Asleep SBP, Week 8 | 116.2 mmHg | Standard Deviation 10.5 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall Systolic Blood Pressure (SBP), Baseline | 122.4 mmHg | Standard Deviation 9.7 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall Diastolic Blood Pressure (DBP), Baseline | 71.9 mmHg | Standard Deviation 7.4 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Awake SBP, Baseline | 125.5 mmHg | Standard Deviation 9 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Asleep SBP, Baseline | 113.9 mmHg | Standard Deviation 12.2 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall SBP, Week 8 | 122.9 mmHg | Standard Deviation 9.5 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Overall DBP, Week 8 | 72.6 mmHg | Standard Deviation 6.2 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) | Awake SBP, Week 8 | 124.9 mmHg | Standard Deviation 10.1 |
Comparison: Overall SBPp-value: 0.92Repeated Measures Analysis
Comparison: Overall DBPp-value: 0.64Repeated Measures Analysis
Comparison: Awake SBPp-value: 0.8Repeated Measures Analysis
Comparison: Asleep SBP at Week 8p-value: 0.97Repeated Measures Analysis
Comparison: Overall SBPp-value: 0.34Repeated Measures Analysis
Comparison: Overall DBPp-value: 0.59Repeated Measures Analysi
Comparison: Awake SBFp-value: 0.57Repeated Measures Analysis
Comparison: Asleep SBPp-value: 0.08Repeated Measures Analysis
Comparison: Overall SBPp-value: 0.59Repeated Measures Analysis
p-value: 0.53Repeated Measures Analysis
Comparison: Awake SBPp-value: 0.55Repeated Measures Analysis
Comparison: Asleep SBPp-value: 0.8Repeated Measures Analysis
Secondary
Mean 24-Hour Ambulatory Blood Pressure (ABP) Nocturnal Dipping
A 24-hour mean ambulatory blood pressure was monitored using a 24 hour ABP device. The ABP device is a small box that is worn on the belt or pant/skirt line with a line that connect under the clothing to the cuff on the upper arm. Blood Pressure was recorded every 30 minutes during the day and every 60 minutes during the night for 24 hours. Nocturnal dipping is the percent change lower between the daytime and nighttime values.
Time frame: Baseline and Week 8
Population: All randomized enrolled participants with complete 24-hour ABP data available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) Nocturnal Dipping | Baseline | 7.3 percent change | Standard Deviation 6.3 |
| Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) Nocturnal Dipping | Week 8 | 7.5 percent change | Standard Deviation 5.7 |
| Placebo- Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) Nocturnal Dipping | Baseline | 7.8 percent change | Standard Deviation 5.1 |
| Placebo- Vitamin D | Mean 24-Hour Ambulatory Blood Pressure (ABP) Nocturnal Dipping | Week 8 | 8.1 percent change | Standard Deviation 6 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) Nocturnal Dipping | Baseline | 8.4 percent change | Standard Deviation 6.8 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) Nocturnal Dipping | Week 8 | 9.2 percent change | Standard Deviation 6.1 |
| Allopurinol | Mean 24-Hour Ambulatory Blood Pressure (ABP) Nocturnal Dipping | Week 8 | 5.2 percent change | Standard Deviation 7.1 |
| Allopurinol | Mean 24-Hour Ambulatory Blood Pressure (ABP) Nocturnal Dipping | Baseline | 7.5 percent change | Standard Deviation 5.3 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) Nocturnal Dipping | Baseline | 9.4 percent change | Standard Deviation 6.2 |
| Placebo- Uric Acid | Mean 24-Hour Ambulatory Blood Pressure (ABP) Nocturnal Dipping | Week 8 | 6.9 percent change | Standard Deviation 6.2 |
p-value: 0.98Repeated Measures Analysis
p-value: 0.07Repeated Measures Analysis
p-value: 0.97Repeated Measures Analysis