Study of Vitamin D and Uric Acid Lowering on Kidney and Blood Vessel Function
Condition: Renal Function; Endothelial Function; Blood Pressure; Overweight; Obesity
MeSH terms: Overweight
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Vitamin D ergocalciferol; Probenecid; Allopurinol; Placebo; Placebo
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): 50,000 unit soft gel capsule once per week for 8 weeks; 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); 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); Placebo soft gel once per week for 8 weeks; Placebo tablet once per day for 4 weeks then twice per day for 4 weeks (eight weeks total)
Other intervention name(s): Vitamin D
Intervention MeSH terms: Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins; Allopurinol; Probenecid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: renin angiotensin system; vitamin D; uric acid; allopurinol; probenecid; endothelial function