- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01635062
The VALIDATE-D Study (VALIDATE-D)
Evaluating Hormonal Mechanisms for Vitamin D Receptor Agonist Therapy in Diabetes: The VALIDATE-D Study
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Massachusetts
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Boston, Massachusetts, United States, 02115
- Brigham and Women's Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Type-Two Diabetes (treated with diet alone, with oral hypoglycemic agents, or with a single injection of basal insulin daily)
- Normal blood pressure, or Mild (Stage 1) Hypertension that is either untreated, or adequately treated with a single anti-hypertensive drug.
- Age >18 years and <70 years
- Estimated GFR > 60ml/min
- Normal laboratory values for: Complete blood count, sodium, potassium, glucose, liver enzymes, urinalysis
- Electrocardiogram without any signs of prior infarction, ventricular conduction abnormality, or supraventricular arrhythmia.
Exclusion Criteria:
- Chronic Kidney Disease or eGFR<60
- History of nephrolithiasis (kidney stones)
- Multiple (more than one) insulin injections daily (since insulin can alter the RAS)
- Poorly controlled type 2 diabetes (That may require more aggressive therapy) as defined by an HbA1c>8.5%
- Type 1 diabetes
- Stage 2 or Stage 3 hypertension or the use of more than 1 antihypertensive drug
- Chronic inflammatory conditions (such as inflammatory bowel disease or arthritis) that are treated with prescribed doses of NSAIDs by a physician.
- The use of prescribed doses of potassium supplements.
- History of liver failure
- History of parathyroid or granulomatous disorders
- History of heart failure, cerebrovascular disease or coronary heart disease
- History of known microvascular complications of diabetes (including retinopathy, neuropathy, nephropathy)
- Illness requiring overnight hospitalization in the past 6 months
- Active tobacco or recreational drug use
- Pregnancy or current breast feeding
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: calcitriol
Subjects will receive calcitriol (titrated up to 0.75 mcg daily) for 3 weeks.
|
Subjects will receive calcitriol (up to 0.75 mcg daily) for 3 weeks.
Other Names:
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Placebo Comparator: placebo
Subjects will receive placebo for 3 weeks.
|
Subjects will receive placebo for 3 weeks.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Change in Circulating RAS Activity After Calcitriol/Placebo Therapy
Time Frame: baseline and 2 weeks following calcitriol/placebo therapy
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The below results represent the change in Plasma Renin Activity.
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baseline and 2 weeks following calcitriol/placebo therapy
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Renal Plasma Flow After Calcitriol/Placebo Therapy
Time Frame: 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.
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baseline and 3 weeks following calcitriol/placebo therapy
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Change in Urine Protein After Calcitriol/Placebo Therapy
Time Frame: 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.
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baseline and 3 weeks following calcitriol/placebo therapy
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2012P000905
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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