The VALIDATE-D Study

NCT ID: NCT01635062

Last Updated: 2017-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2015-12-31

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.

Conditions

Type 2 Diabetes; Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

calcitriol

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

Group Type: EXPERIMENTAL

Calcitriol

Intervention Type: DRUG

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

placebo

Subjects will receive placebo for 3 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Subjects will receive placebo for 3 weeks.

Interventions

Calcitriol

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

Intervention Type: DRUG

Placebo

Subjects will receive placebo for 3 weeks.

Intervention Type: DRUG

Other Intervention Names

1,25-dihydroxyvitamin D3

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Anand Vaidya

Assistant Professor of Medicine, Harvard Medical School

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anand Vaidya, MD, MMSc

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital, Harvard Medical School

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 23971740 (View on PubMed)

Other Identifiers

2012P000905

Identifier Type: -

Identifier Source: org_study_id