Does Thiazolidinedione Therapy Improve Endothelial Function and Preserve Renal Function

This study has been terminated.

(Low enrollment because of the specifics of the inclusion criteria)

Sponsor:

Information provided by (Responsible Party):

Patricia J M Best, Mayo Clinic

ClinicalTrials.gov Identifier:

NCT00586261

First received: December 21, 2007

Last updated: March 13, 2013

Last verified: March 2013

History of Changes

Tracking Information

First Received Date ^ICMJE

December 21, 2007

Last Updated Date

March 13, 2013

Start Date ^ICMJE

March 2006

Primary Completion Date

January 2009 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Change in Brachial Arterial Reactivity [ Time Frame: After 6 months of treatment ] [ Designated as safety issue: No ]

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.

Original Primary Outcome Measures ^ICMJE

Change in brachial reactivity [ Time Frame: After 6 months of treatment ] [ Designated as safety issue: No ]
Change in C-reactive protein [ Time Frame: After 6 months of treatment ] [ Designated as safety issue: No ]
Change in creatinine clearance measured by 24 hour urine creatinine [ Time Frame: After 6 months of treatment ] [ Designated as safety issue: No ]

Change History

Complete list of historical versions of study NCT00586261 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Not Provided

Original Secondary Outcome Measures ^ICMJE

Change in pulse wave velocity and augmentation index [ Time Frame: After 6 months of treatment ] [ Designated as safety issue: No ]
Change in serum F2-isoprostanes [ Time Frame: After 6 months of treatment ] [ Designated as safety issue: No ]
Change in urea clearance [ Time Frame: After 6 months of treatment ] [ Designated as safety issue: No ]
Change in estimated glomerular filtration rate by the simplified MDRD equation [ Time Frame: After 6 months of treatment ] [ Designated as safety issue: No ]
Change in degree of microalbuminuria [ Time Frame: After 6 months of treatment ] [ Designated as safety issue: No ]
Number of cardiovascular events within 6 months including death, myocardial infarction, revascularization, or stroke [ Time Frame: After 6 months of treatment ] [ Designated as safety issue: No ]

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

Does Thiazolidinedione Therapy Improve Endothelial Function and Preserve Renal Function

Official Title ^ICMJE

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

Brief Summary

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.

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:

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)
To determine the effects chronic pioglitazone therapy on inflammation and oxidative stress in non-diabetic patients with CKD
To determine the effects chronic pioglitazone therapy on progression of renal disease in non-diabetic patients with CKD

Study Type ^ICMJE

Interventional

Study Phase

Not Provided

Study Design ^ICMJE

Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment

Condition ^ICMJE

Chronic Kidney Disease

Intervention ^ICMJE

Drug: Pioglitazone
Pioglitazone 30 mg daily for 6 months

Other Name: Actos
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 Name: Nitrostat

Study Arm (s)

Placebo Comparator: Placebo
Placebo 30 mg daily for 6 months, nitroglycerin was given to check the brachial reactivity.
Interventions:
- Drug: Placebo
- Drug: Nitroglycerin
Active Comparator: Pioglitazone
Pioglitazone 30 mg daily for 6 months, nitroglycerin was given to check the brachial reactivity.
Interventions:
- Drug: Pioglitazone
- Drug: Nitroglycerin

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Terminated

Enrollment ^ICMJE

Completion Date

July 2009

Primary Completion Date

January 2009 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Gender

Both

Ages

18 Years and older

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Location Countries ^ICMJE

United States

Administrative Information

NCT Number ^ICMJE

NCT00586261

Other Study ID Numbers ^ICMJE

06-002245

Has Data Monitoring Committee

Responsible Party

Patricia J M Best, Mayo Clinic

Study Sponsor ^ICMJE

Mayo Clinic

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Principal Investigator:

Patricia M. Best, M.D.

Mayo Clinic

Information Provided By

Mayo Clinic

Verification Date

March 2013

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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