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This study has been completed.
Information provided by (Responsible Party):
Anand Vaidya, Brigham and Women's Hospital Identifier:
First received: July 2, 2012
Last updated: September 16, 2016
Last verified: September 2016
The purpose of this study is to evaluate whether vitamin D receptor agonist therapy lowers renin-angiotensin system activity.

Condition Intervention
Type 2 Diabetes
Drug: Calcitriol and Lisinopril
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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 Brigham and Women's Hospital:

Primary Outcome Measures:
  • Circulating RAS activity after calcitriol/placebo therapy [ Time Frame: before 2017 ]

Secondary Outcome Measures:
  • Renal-vascular tissue RAS activity after calcitriol/placebo therapy [ Time Frame: before 2017 ]
  • Renal-vascular RAS activity and urine protein after calcitriol/lisinopril therapy [ Time Frame: before 2017 ]
  • Adiponectin levels [ Time Frame: Before 2017 ]
  • Adipose-tissue RAS measures [ Time Frame: before 2017 ]

Enrollment: 40
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
Drug: Calcitriol and Lisinopril
Subjects will receive calcitriol and lisinopril to evaluate their influence on the renin-angiotensin system when compared to placebo.
Placebo Comparator: placebo
Drug: Placebo
Placebo will be given

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 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.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT01635062

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

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Anand Vaidya, Assistant Professor of Medicine, Harvard Medical School, Brigham and Women's Hospital Identifier: NCT01635062     History of Changes
Other Study ID Numbers: 2012P000905
Study First Received: July 2, 2012
Last Updated: September 16, 2016

Additional relevant MeSH terms:
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs
Calcium Channel Agonists
Membrane Transport Modulators
Vasoconstrictor Agents
Growth Substances
Bone Density Conservation Agents processed this record on March 28, 2017