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
  Purpose

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.


Condition Intervention
Chronic Kidney Disease
Drug: Pioglitazone
Drug: Placebo
Drug: Nitroglycerin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Does Chronic Thiazolidinedione Therapy Improve Endothelial Function and Preserve Renal Function in Non-Diabetic Patients With Chronic Kidney Disease?

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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.


Enrollment: 36
Study Start Date: March 2006
Study Completion Date: July 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Nitrostat
Active Comparator: Pioglitazone
Pioglitazone 30 mg daily for 6 months, nitroglycerin was given to check the brachial reactivity.
Drug: Pioglitazone
Pioglitazone 30 mg daily for 6 months
Other Name: Actos
Drug: Nitroglycerin
0.4 mg sublingual nitroglycerin tablet was given to all patients without a contraindication to check the brachial reactivity.
Other Name: Nitrostat

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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00586261

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Patricia M. Best, M.D. Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Patricia J M Best, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00586261     History of Changes
Other Study ID Numbers: 06-002245
Study First Received: December 21, 2007
Results First Received: November 13, 2012
Last Updated: March 13, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
Kidney Failure, Chronic
Renal Insufficiency, Chronic
Proteinuria
Albuminuria

Additional relevant MeSH terms:
Renal Insufficiency, Chronic
Kidney Diseases
Renal Insufficiency
Urologic Diseases
Pioglitazone
2,4-thiazolidinedione
Nitroglycerin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014