Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

December 21, 2007
March 13, 2013
March 2006
January 2009   (final data collection date for primary outcome measure)
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.
  • 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 ]
Complete list of historical versions of study NCT00586261 on ClinicalTrials.gov Archive Site
Not Provided
  • 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 ]
Not Provided
Not Provided
 
Does Thiazolidinedione Therapy Improve Endothelial Function and Preserve Renal Function
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.

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
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Chronic Kidney Disease
  • 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
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
36
July 2009
January 2009   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00586261
06-002245
No
Patricia J M Best, Mayo Clinic
Mayo Clinic
Not Provided
Principal Investigator: Patricia M. Best, M.D. Mayo Clinic
Mayo Clinic
March 2013

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