The VALIDATE-D Study

Brigham and Women's Hospital41 enrolled

Overview

The purpose of this study is to evaluate whether vitamin D receptor agonist therapy lowers renin-angiotensin system activity.

This study aims to evaluate whether vitamin D receptor agonist therapy (calcitriol) in diabetes lowers renin-angiotensin system (RAS) activity in a manner similar to an ACE inhibitor. This is a physiology study, focused on evaluating hormonal changes in the circulating and tissue RAS when compared to placebo. Subjects with type 2 diabetes and obesity and normal kidney function will undergo evaluation of their circulating and renal-vascular RAS activity and urinary protein at baseline, after withdrawing interfering medications, while on a controlled electrolyte diet, and in controlled posture settings. They will then randomly receive a study medication (calcitriol or placebo) for 3 weeks followed by a re-assessment of their RAS parameters. The main outcomes that will be evaluated following calcitriol/placebo include measures of the circulating renin activity (primary), as well as measures of the renal-vascular RAS (renal plasma flow) and urine protein (secondary) The primary outcome is the change in the plasma renin activity when sodium restricted, before and after intervention. Secondary outcomes include the change in renal plasma flow and urine protein when sodium loaded, before and after intervention.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

Conditions

Type 2 Diabetes Obesity

Interventions

CalcitriolDRUG

Subjects will receive calcitriol (up to 0.75 mcg daily) for 3 weeks.

PlaceboDRUG

Subjects will receive placebo for 3 weeks.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Type-Two Diabetes (treated with diet alone, with oral hypoglycemic agents, or with a single injection of basal insulin daily) 2. Normal blood pressure, or Mild (Stage 1) Hypertension that is either untreated, or adequately treated with a single anti-hypertensive drug. 3. Age \>18 years and \<70 years 4. Estimated GFR \> 60ml/min 5. Normal laboratory values for: Complete blood count, sodium, potassium, glucose, liver enzymes, urinalysis 6. Electrocardiogram without any signs of prior infarction, ventricular conduction abnormality, or supraventricular arrhythmia. Exclusion Criteria: 1. Chronic Kidney Disease or eGFR\<60 2. History of nephrolithiasis (kidney stones) 3. Multiple (more than one) insulin injections daily (since insulin can alter the RAS) 4. Poorly controlled type 2 diabetes (That may require more aggressive therapy) as defined by an HbA1c\>8.5% 5. Type 1 diabetes 6. Stage 2 or Stage 3 hypertension or the use of more than 1 antihypertensive drug 7. Chronic inflammatory conditions (such as inflammatory bowel disease or arthritis) that are treated with prescribed doses of NSAIDs by a physician. 8. The use of prescribed doses of potassium supplements. 9. History of liver failure 10. History of parathyroid or granulomatous disorders 11. History of heart failure, cerebrovascular disease or coronary heart disease 12. History of known microvascular complications of diabetes (including retinopathy, neuropathy, nephropathy) 13. Illness requiring overnight hospitalization in the past 6 months 14. Active tobacco or recreational drug use 15. Pregnancy or current breast feeding

Locations (1)

Brigham and Women's Hospital

Boston, Massachusetts, United States

Outcomes

Primary Outcomes

The Change in Circulating RAS Activity After Calcitriol/Placebo Therapy

The below results represent the change in Plasma Renin Activity.

Time frame: baseline and 2 weeks following calcitriol/placebo therapy

Secondary Outcomes

Change in Renal Plasma Flow After Calcitriol/Placebo Therapy

Subjects had their renal plasma flow assessed at baseline while sodium loaded, and again after 3 weeks of randomized therapy with either calcitriol (up to 0.75 mcg daily) or placebo.

Time frame: baseline and 3 weeks following calcitriol/placebo therapy

Change in Urine Protein After Calcitriol/Placebo Therapy

Subjects have their urine protein assessed at baseline while sodium loaded and again 3 weeks after randomized therapy with calcitriol or placebo.

Time frame: baseline and 3 weeks following calcitriol/placebo therapy

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.