Study of Vitamin D and Uric Acid Lowering on Kidney and Blood Vessel Function

NCT01320722 | Completed Phase 3 Results

• 2 other identifiers: 2010-P-0020491R01HL105440
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Function; Endothelial Function; Blood Pressure; Overweight; Obesity

Keywords

renin angiotensin system; vitamin D; uric acid; allopurinol; probenecid; endothelial function

Outcome Measures

Primary Outcomes (6)

• 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.

  Week 8 (pre and post captopril)

• 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.

  Week 8

• 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.

  Week 8

• 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.

  Week 8 (pre and post captopril)

• 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.

  Week 8

• 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.

  Week 8

Secondary Outcomes (3)

• Change in Endothelium-Dependent Vasodilation (EDV)

  Baseline and Week 8 (pre and post ischaemic stimulus)

• Mean 24-Hour Ambulatory Blood Pressure (ABP)

  Baseline and Week 8

• Mean 24-Hour Ambulatory Blood Pressure (ABP) Nocturnal Dipping

  Baseline and Week 8

Study Arms (5)

Vitamin D

EXPERIMENTAL

Vitamin D ergocalciferol 50,000 unit soft gel capsule once per week for 8 weeks.

Drug: Vitamin D ergocalciferol

Probenecid

EXPERIMENTAL

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).

Drug: Probenecid

Allopurinol

EXPERIMENTAL

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).

Drug: Allopurinol

Placebo- Vitamin D

PLACEBO COMPARATOR

Placebo soft gel once per week for 8 weeks.

Drug: Placebo

Placebo- Uric Acid

PLACEBO COMPARATOR

Placebo tablet once per day for 4 weeks then twice per day for 4 weeks (eight weeks total).

Drug: Placebo

Interventions

Vitamin D ergocalciferol DRUG

50,000 unit soft gel capsule once per week for 8 weeks

Also known as: Vitamin D

Vitamin D

Probenecid DRUG

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)

Probenecid

Allopurinol DRUG

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)

Allopurinol

Placebo DRUG

Placebo soft gel once per week for 8 weeks

Placebo- Vitamin D

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (OH)D \< 20 ng/mL OR Uric acid ≥ 5 mg/dL
• Age ≥ 18, ≤ 75 years
• Body Mass Index (BMI) ≥ 25 kg/m\^2

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Overweight; Obesity

Interventions

Ergocalciferols; Vitamin D; Probenecid; Allopurinol

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Secosteroids; Membrane Lipids; Lipids; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: John P Forman, MD
• Organization: Brigham and Women's Hospital

jforman@partners.org

Study Officials

• John P Forman, MD, MSc

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: INSTRUCTOR IN MEDICINE, BRIGHAM AND WOMEN'S HOSPITAL

Study Record Dates

• First Submitted: March 21, 2011
• First Posted: March 22, 2011
• Study Start: March 1, 2011
• Primary Completion: May 1, 2015
• Study Completion: June 1, 2015
• Last Updated: June 29, 2017
• Results First Posted: June 29, 2017

Record last verified: 2017-05

Locations

US (1)