Effect Of Paricalcitol (Zemplar) On Endothelial Function And Inflammation In Type 2 Diabetes And Chronic Kidney Disease

February 12, 2013 updated by: Vasudevan Raghavan, Scott and White Hospital & Clinic

EFFECT OF PARICALCITOL (ZEMPLAR) ON ENDOTHELIAL FUNCTION AND INFLAMMATION IN TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE

The purpose of this research study is to study the effects of paricalcitol on endothelial function and inflammation, cardiovascular risk factors which are associated with patient populations that have Type 2 diabetes and Stage 3 and 4 Chronic Kidney Disease (CKD).

Hypothesis 1: The state of CKD is associated with oxidative stress and inflammation and impaired post ischemic endothelium dependent flow mediated vasodilation which may contribute to atherogenesis.

Hypothesis 2: The administration of paracalcitol to patients with CKD will suppress oxidative stress and inflammation and improve endothelial function and thus contribute to an anti-atherogenic action.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Emory University
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Joslin Diabetes Clinic, Inc.
    • Nebraska
      • Omaha, Nebraska, United States, 68105
        • Omaha VA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients with Type 2 diabetes and CKD
  2. Age 18 - 70 years
  3. Stable anti-hypertensive and lipid lowering therapy for at least 2 months. All patients should be on an ACEI or ARB unless contraindicated because of side effects (standard of care). No changes in lipid lowering therapy during the 3 months of this study. Blood pressure doses may be changed but new therapy with ACE inhibitors will not be allowed.

Exclusion Criteria:

  1. Severe co morbid conditions - e.g. Cancer, etc.
  2. Congestive heart failure.
  3. Inability to give informed consent or attend study related visits.
  4. Have a history of abnormally high vitamin D or calcium levels in the bloodstream.
  5. Unwilling or unable to complete screening or data collection procedures.
  6. Have a known allergy to the study drug.
  7. Pregnant or breast feeding
  8. Plasma Calcium >9 mg/dl
  9. Patients should discontinue any calcium supplementation prior to entry into the study.
  10. Other vitamin D analogs (eg Sensipar) and vitamin D preparations are contraindicated

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Zemplar
Zemplar 1 mcg or placebo to be taken once daily with breakfast for 3 months
Drug: Zemplar
Zemplar 1 mcg or placebo to be taken once daily with breakfast for 3 months
Placebo Comparator: Placebo
Zemplar 1 mcg or placebo to be taken once daily with breakfast for 3 months
Drug: Placebo
Zemplar 1 mcg or placebo to be taken once daily with breakfast for 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The change in brachial artery Flow Mediated Dilataion with paracalcitol (1mcg/day)compared with placebo for 3 months.
Time Frame: Baseline, 4 weeks, and 12 weeks
We therefore propose a study of the effects of Zemplar compared to placebo in patients with diabetes and stage 3-4 CKD on endothelial function and markers of inflammation and oxidative stress. The finding will help not only guide and encourage such treatment in similar patients, but will give us fundamental mechanistic insights into the role of vitamin D in the pathogenesis of diabetes and CVD.
Baseline, 4 weeks, and 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biomarker Measurement
Time Frame: Baseline, 4 weeks, and 12 weeks

Determine the prevalance of abnormalities in biomarkers of inflammation, oxidative stress and endothelial function in patients with CKD compared to a healthy population

The following are the biomarkers of inflammation and oxidative stress to be measured in the secondary outcomes are:

NFkB binding by mononuclear cells (MNC) ; ROS generation and p47phox expression by MNC plasma concentration of MMP-9, MCP-1, ICAM-1, IL-6 , CRP, ADMA and nitrotyrosine.. urinary isoprostane and plasma Nitrotyrosine in patients with CKD.
Baseline, 4 weeks, and 12 weeks
Biomarker Measurement
Time Frame: Baseline, 4 weeks, and 12 weeks

Compare the change in biomarkers of inflammation, oxidative stress and endothelial function with paracalcitol (1mcg/day) compared with placebo for 3 months in patients with CKD.

The following are the biomarkers of inflammation and oxidative stress to be measured in the secondary outcomes are:

NFkB binding by mononuclear cells (MNC) ; ROS generation and p47phox expression by MNC plasma concentration of MMP-9, MCP-1, ICAM-1, IL-6 , CRP, ADMA and nitrotyrosine.. urinary isoprostane and plasma Nitrotyrosine in patients with CKD.
Baseline, 4 weeks, and 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Scott and White Hospital & Clinic

Collaborators

Abbott

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (Actual)

November 1, 2012

Study Completion (Anticipated)

February 1, 2013

Study Registration Dates

First Submitted

February 29, 2012

First Submitted That Met QC Criteria

February 12, 2013

First Posted (Estimate)

February 15, 2013

Study Record Updates

Last Update Posted (Estimate)

February 15, 2013

Last Update Submitted That Met QC Criteria

February 12, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 81890

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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