The VALIDATE-D Study

Obesity Clinical Trial

— VALIDATE-D  

Official title:

Evaluating Hormonal Mechanisms for Vitamin D Receptor Agonist Therapy in Diabetes: The VALIDATE-D Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01635062
• Other study ID #: 2012P000905
• Status: Completed
• Phase: N/A
• First received: July 2, 2012
• Last updated: September 16, 2016
• Start date: September 2012
• Est. completion date: December 2015

Study information

• Verified date: September 2016
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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 RAS (primary), as well as measures of the renal-vascular RAS, urine protein, adipocytokine levels, and adipose-tissue RAS activity (secondary)

In an extension phase, Lisinopril will be added to the study drug for another 2 weeks followed by another assessment of the primary and secondary outcome parameters, and subjects will continue lisinopril+study drug for 3 additional months for one final assessment of RAS parameters and urinary protein.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Obesity
• Type 2 Diabetes

Intervention

Drug:
• Calcitriol and Lisinopril
Subjects will receive calcitriol and lisinopril to evaluate their influence on the renin-angiotensin system when compared to placebo.
• Placebo
Placebo will be given

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Circulating RAS activity after calcitriol/placebo therapy		before 2017	No
Secondary	Renal-vascular tissue RAS activity after calcitriol/placebo therapy		before 2017	No
Secondary	Renal-vascular RAS activity and urine protein after calcitriol/lisinopril therapy		before 2017	No
Secondary	Adiponectin levels		Before 2017	No
Secondary	Adipose-tissue RAS measures		before 2017	No