The VALDIATE-D Study (VALIDATE-D)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Brigham and Women's Hospital
Sponsor:
Information provided by (Responsible Party):
Anand Vaidya, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT01635062
First received: July 2, 2012
Last updated: January 16, 2014
Last verified: January 2014
  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 and Lisinopril
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Renal-vascular tissue RAS activity after calcitriol/placebo therapy [ Time Frame: before 2017 ] [ Designated as safety issue: No ]
  • Renal-vascular RAS activity and urien protein after calcitriol/lisinopril therapy [ Time Frame: before 2017 ] [ Designated as safety issue: No ]
  • Adiponectin levels [ Time Frame: Before 2017 ] [ Designated as safety issue: No ]
  • Adipose-tissue RAS measures [ Time Frame: before 2017 ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: September 2012
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01635062

Contacts
Contact: Kristina Secinaro, RD 617-278-0305
Contact: Anand Vaidya, MD, MMSc 617-525-8285

Locations
United States, Massachusetts
Brigham and Women's Hospital Recruiting
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

No publications provided

Responsible Party: Anand Vaidya, Instructor in Medicine, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01635062     History of Changes
Other Study ID Numbers: 2012P000905
Study First Received: July 2, 2012
Last Updated: January 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Lisinopril
Calcitriol
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs
Calcium Channel Agonists
Membrane Transport Modulators
Vasoconstrictor Agents
Vitamins
Micronutrients
Growth Substances
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on September 18, 2014