Does Thiazolidinedione Therapy Improve Endothelial Function and Preserve Renal Function

March 13, 2013 updated by: Patricia J M Best, Mayo Clinic

Does Chronic Thiazolidinedione Therapy Improve Endothelial Function and Preserve Renal Function in Non-Diabetic Patients With Chronic Kidney Disease?

The hypothesis of the current proposal is that chronic pioglitazone therapy will result in improved endothelial function, decreased inflammation, and preservation of renal function in patients with CKD but without diabetes.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Despite continued improvements in the outcomes of patients with cardiovascular disease, similar improvements have not been seen in patients with chronic kidney disease (CKD). CKD constitutes one of the highest risk populations for cardiovascular disease. When the creatinine clearance is ≤ 60 ml/min the risk for cardiovascular events is greater than that of diabetes. However, few studies have focused on the prevention or treatment of coronary artery disease (CAD) in CKD patients.

The development of endothelial dysfunction and increased inflammation appear to be critical in the development of atherosclerosis and cardiovascular disease. The broad long-term objective of this grant proposal is to determine unique therapies to reduce endothelial dysfunction and inflammation, and thereby help to prevent cardiovascular disease and preserve renal function in patients with CKD. Thiazolidinediones such as pioglitazone appear to improve endothelial function and decrease inflammation, an effect that may be present in patients with or without diabetes.

To address this hypothesis the following Specific Aims are proposed:

  1. To determine the effects of chronic pioglitazone therapy on endothelial function in non-diabetic patients with CKD (creatinine clearance ≤ 60 ml/ min, but not on dialysis)
  2. To determine the effects chronic pioglitazone therapy on inflammation and oxidative stress in non-diabetic patients with CKD
  3. To determine the effects chronic pioglitazone therapy on progression of renal disease in non-diabetic patients with CKD

Study Type

Interventional

Enrollment (Actual)

36

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
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age over 18 years.
  • Creatinine clearance ≤ 60 ml/min by the Cockcroft-Gault equation
  • Patients not anticipated to go on dialysis or have renal transplantation in the next 6 months
  • Ability to provide informed consent
  • Life expectancy greater than 12 months

Exclusion Criteria:

  • Diabetes mellitus or a fasting blood glucose ≥ 110 mg/dL
  • Acute renal failure
  • Class 3 or 4 heart failure
  • Liver failure, ascites, or an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) two times the upper limit of normal
  • Hemoglobin less than 9 mg/dL
  • Multiple myeloma
  • Premenopausal women not using at least 1 form of birth control
  • Pregnant or nursing women
  • Prisoners
  • Known allergy to pioglitazone

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo 30 mg daily for 6 months, nitroglycerin was given to check the brachial reactivity.
Drug: Placebo
Placebo 30 mg daily for 6 months
Drug: Nitroglycerin
0.4 mg sublingual nitroglycerin tablet was given to all patients without a contraindication to check the brachial reactivity.
Other Names:
  • Nitrostat
Active Comparator: Pioglitazone
Pioglitazone 30 mg daily for 6 months, nitroglycerin was given to check the brachial reactivity.
Drug: Nitroglycerin
0.4 mg sublingual nitroglycerin tablet was given to all patients without a contraindication to check the brachial reactivity.
Other Names:
  • Nitrostat
Drug: Pioglitazone
Pioglitazone 30 mg daily for 6 months
Other Names:
  • Actos

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Brachial Arterial Reactivity
Time Frame: After 6 months of treatment
Brachial arterial reactivity was measured by ultrasound. A blood pressure cuff was placed around the right forearm. Using the ultrasound probe of the ultrasound, 2-dimensional images clearly defining the anterior and posterior intimal wall of the brachial artery were collected. Flow velocities were then measured using pulsed wave Doppler. The blood pressure cuff previously placed around the patient's right forearm was inflated to 200 mmHg. The cuff remained inflated for 5 minutes as the patient remained motionless and quiet. Prior to deflation, the patient was asked to remain still as flow velocities and 2-dimensional images were obtained immediately following cuff deflation. Then a 0.4 mg sublingual nitroglycerin tablet was given to all patients without a contraindication and all measurements were repeated.
After 6 months of treatment

Collaborators and Investigators

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

Sponsor

Mayo Clinic

Investigators

  • Principal Investigator: Patricia M. Best, M.D., Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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

March 1, 2006

Primary Completion (Actual)

January 1, 2009

Study Completion (Actual)

July 1, 2009

Study Registration Dates

First Submitted

December 21, 2007

First Submitted That Met QC Criteria

December 21, 2007

First Posted (Estimate)

January 4, 2008

Study Record Updates

Last Update Posted (Estimate)

March 15, 2013

Last Update Submitted That Met QC Criteria

March 13, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06-002245

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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