Study of Vitamin D and Uric Acid Lowering on Kidney and Blood Vessel Function (MODERATE)
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ClinicalTrials.gov Identifier: NCT01320722 |
Recruitment Status
:
Completed
First Posted
: March 22, 2011
Results First Posted
: June 29, 2017
Last Update Posted
: June 29, 2017
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Renal Function Endothelial Function Blood Pressure Overweight Obesity | Drug: Vitamin D ergocalciferol Drug: Probenecid Drug: Allopurinol Drug: Placebo | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 242 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | Modifiable Effectors of Renin System Activation: Treatment Evaluation (MODERATE) |
Study Start Date : | March 2011 |
Actual Primary Completion Date : | May 2015 |
Actual Study Completion Date : | June 2015 |

Arm | Intervention/treatment |
---|---|
Experimental: Vitamin D
Vitamin D ergocalciferol 50,000 unit soft gel capsule once per week for 8 weeks.
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Drug: Vitamin D ergocalciferol
50,000 unit soft gel capsule once per week for 8 weeks
Other Name: Vitamin D
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Experimental: 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).
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Drug: 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)
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Experimental: 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).
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Drug: 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)
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Placebo Comparator: Placebo- Vitamin D
Placebo soft gel once per week for 8 weeks.
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Drug: Placebo
Placebo soft gel once per week for 8 weeks
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Placebo Comparator: Placebo- Uric Acid
Placebo tablet once per day for 4 weeks then twice per day for 4 weeks (eight weeks total).
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Drug: Placebo
Placebo tablet once per day for 4 weeks then twice per day for 4 weeks (eight weeks total)
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- Change in Renal Plasma Flow (RPF) in Response to Captopril in High Sodium Balance [Vitamin D] [ Time Frame: 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] [ Time Frame: 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.
- Angiotensin II (ATII) Concentration [Vitamin D] [ Time Frame: 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] [ Time Frame: 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] [ Time Frame: 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.
- Angiotensin II (ATII) Concentration [Uric Acid] [ Time Frame: 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 Endothelium-Dependent Vasodilation (EDV) [ Time Frame: 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.
- Mean 24-Hour Ambulatory Blood Pressure (ABP) [ Time Frame: 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 [ Time Frame: 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.

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Ages Eligible for Study: | 18 Years to 75 Years (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01320722
United States, Massachusetts | |
Brigham and Women's Hospital | |
Boston, Massachusetts, United States, 02115 |
Principal Investigator: | John P Forman, MD, MSc | Brigham and Women's Hospital |
Responsible Party: | John P. Forman, INSTRUCTOR IN MEDICINE, BRIGHAM AND WOMEN'S HOSPITAL, Brigham and Women's Hospital |
ClinicalTrials.gov Identifier: | NCT01320722 History of Changes |
Other Study ID Numbers: |
2010-P-002049 1R01HL105440 ( U.S. NIH Grant/Contract ) |
First Posted: | March 22, 2011 Key Record Dates |
Results First Posted: | June 29, 2017 |
Last Update Posted: | June 29, 2017 |
Last Verified: | May 2017 |
Keywords provided by John P. Forman, Brigham and Women's Hospital:
renin angiotensin system vitamin D uric acid |
allopurinol probenecid endothelial function |
Additional relevant MeSH terms:
Overweight Body Weight Signs and Symptoms Vitamins Vitamin D Ergocalciferols Allopurinol Probenecid Uric Acid Micronutrients Growth Substances Physiological Effects of Drugs |
Bone Density Conservation Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Enzyme Inhibitors Gout Suppressants Antirheumatic Agents Free Radical Scavengers Antioxidants Protective Agents Uricosuric Agents Renal Agents |