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The VALIDATE-D Study (VALIDATE-D)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01635062
First Posted: July 6, 2012
Last Update Posted: April 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Anand Vaidya, Brigham and Women's Hospital
  Purpose
The purpose of this study is to evaluate whether vitamin D receptor agonist therapy lowers renin-angiotensin system activity.

Condition Intervention
Type 2 Diabetes Obesity Drug: Calcitriol Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Evaluating Hormonal Mechanisms for Vitamin D Receptor Agonist Therapy in Diabetes: The VALIDATE-D Study

Resource links provided by NLM:


Further study details as provided by Anand Vaidya, Brigham and Women's Hospital:

Primary Outcome Measures:
  • The Change in Circulating RAS Activity After Calcitriol/Placebo Therapy [ Time Frame: baseline and 2 weeks following calcitriol/placebo therapy ]
    The below results represent the change in Plasma Renin Activity.


Secondary Outcome Measures:
  • 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.

  • 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.


Enrollment: 41
Study Start Date: September 2012
Study Completion Date: December 2015
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: calcitriol
Subjects will receive calcitriol (titrated up to 0.75 mcg daily) for 3 weeks.
Drug: Calcitriol
Subjects will receive calcitriol (up to 0.75 mcg daily) for 3 weeks.
Other Name: 1,25-dihydroxyvitamin D3
Placebo Comparator: placebo
Subjects will receive placebo for 3 weeks.
Drug: Placebo
Subjects will receive placebo for 3 weeks.

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01635062


Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
Principal Investigator: Anand Vaidya, MD, MMSc Brigham and Women's Hospital, Harvard Medical School
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Anand Vaidya, Assistant Professor of Medicine, Harvard Medical School, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01635062     History of Changes
Other Study ID Numbers: 2012P000905
First Submitted: July 2, 2012
First Posted: July 6, 2012
Results First Submitted: January 6, 2017
Results First Posted: April 11, 2017
Last Update Posted: April 11, 2017
Last Verified: February 2017

Additional relevant MeSH terms:
Calcitriol
Dihydroxycholecalciferols
Calcium Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents