The VALIDATE-D Study

Not Applicable

Completed

• Conditions: Type 2 Diabetes; Obesity
• Interventions: Drug: Placebo; Drug: Calcitriol

• Registration Number: NCT01635062
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

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

Detailed Description

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 Timeline

• Study First Submitted: 2012-07-02
• Study First Submitted QC: 2012-07-03
• Study First Posted: 2012-07-06
• Study Start: 2012-09
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Results First Submitted: 2017-01-06
• Status Verified: 2017-02
• Results First Submitted QC: 2017-02-28
• Last Update Submitted: 2017-02-28
• Results First Posted: 2017-04-11
• Last Update Posted: 2017-04-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

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.

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	Subjects will receive placebo for 3 weeks.
calcitriol	Calcitriol	Subjects will receive calcitriol (titrated up to 0.75 mcg daily) for 3 weeks.

Primary Outcome Measures

Name	Time	Method
The Change in Circulating RAS Activity After Calcitriol/Placebo Therapy	baseline and 2 weeks following calcitriol/placebo therapy	The below results represent the change in Plasma Renin Activity.

Secondary Outcome Measures

Name	Time	Method
Change in Renal Plasma Flow After Calcitriol/Placebo Therapy	baseline and 3 weeks following 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.
Change in Urine Protein After Calcitriol/Placebo Therapy	baseline and 3 weeks following 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.

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States