Clinical trial NCT01635062: The VALIDATE-D Study
Official title: Evaluating Hormonal Mechanisms for Vitamin D Receptor Agonist Therapy in Diabetes: The VALIDATE-D Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes
Obesity
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2012-07-06
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: The Change in Circulating RAS Activity After Calcitriol/Placebo Therapy
timeFrame: baseline and 2 weeks following calcitriol/placebo therapy
Secondary outcomes:
measure: Change in Renal Plasma Flow After Calcitriol/Placebo Therapy
timeFrame: baseline and 3 weeks following calcitriol/placebo therapy
measure: Change in Urine Protein After Calcitriol/Placebo Therapy
timeFrame: baseline and 3 weeks following calcitriol/placebo therapy
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital, Harvard Medical School
name: Anand Vaidya, MD, MMSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brown JM, Secinaro K, Williams JS, Vaidya A. Evaluating hormonal mechanisms of vitamin D receptor agonist therapy in diabetic kidney disease: the VALIDATE-D study. BMC Endocr Disord. 2013 Aug 23;13:33. doi: 10.1186/1472-6823-13-33.