The VALIDATE-D Study

Mass General Brigham

Status: Completed

Conditions: Obesity; Type 2 Diabetes

Treatments: Drug: Placebo; Drug: Calcitriol

Study type: Interventional

Funder types: Other

Identifiers

NCT01635062

2012P000905

Details and patient eligibility

About

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

Full 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.

Enrollment: 41 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

41 participants in 2 patient groups, including a placebo group

calcitriol

Experimental group

Description:

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

Treatment:

Drug: Calcitriol

placebo

Placebo Comparator group

Description:

Subjects will receive placebo for 3 weeks.

Treatment:

Drug: Placebo