Prevention of Instent Renarrowing With Aggressive Glucose Lowering With Pioglitazone in Diabetic Patients (PPAR-G)

January 6, 2009 updated by: Queen Elizabeth II Health Sciences Centre

Prevention of Neointimal Proliferation With Aggressive Reduction of Glucose Concentrations (Pioglitazone) Study -- PPAR-G -- An IVUS Pilot Feasibility Study in Type 2 Diabetic Patients.

Patients with diabetes have worse outcomes after percutaneous coronary intervention (PCI) procedures, compared to those patients without diabetes. They are at increased risk of death, heart attack, or needing further procedures due to renarrowing of their coronary narrowings after implantation of a coronary stent. Studies have suggested that poor control of diabetes may be partly responsible for these poor outcomes. Thiazolidinedione drugs, such as pioglitazone, can improve the diabetes control and make the patient more sensitive to the effects of insulin. Preliminary studies suggest that pioglitazone may also help prevent renarrowing after PCI.

This study was a pilot study designed to determine whether more aggressive treatment of the diabetes with the routine use of the drug pioglitazone (30mg/day for 6 months), in addition to the patient's usual diabetic medications adjusted to optimize their diabetic control (get glycated hemoglobin < 7%), could reduce the amount of tissue buildup within the stent after 6 months, compared to a group less aggressively treated without pioglitazone and their usual medications for diabetes.

An intravascular ultrasound probe was used to assess the extent of tissue buildup within the stent and this was performed immediately after the PCI as a baseline and repeated after 6 months of therapy.

The investigators hypothesize that the more aggressive diabetic treatment with pioglitazone would reduce the extent of tissue growth within the stent after 6 months of therapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background: Despite drug-eluting stents (DES), diabetic patients remain at high risk of restenosis and poor clinical outcomes after percutaneous coronary intervention (PCI). Studies have suggested poor glycemic control and insulin resistance may be predictors of poor outcomes after PCI. There are conflicting studies as to whether strategies to improve glycemic control can improve outcomes after PCI. Thiazolidinediones, such as pioglitazone (PIO), may have anti-restenotic benefits, independent of glycemic control.

Study design: This study was a single centre prospective, randomized, open-label, blinded-endpoint (PROBE) parallel design trial. Type 2 diabetic patients, treated with diet or oral antidiabetic medication (sulfonylurea vs. metformin or combination; but no thiazolidinedione or insulin), who are undergoing elective or urgent PCI with stenting were eligible. Fifty type 2 diabetic patients were randomly assigned to either: intensive glycemic control: pioglitazone (PIO; 30 mg/d x 6 months) in addition to titration of oral hypoglycemic agents (OHA) to get HbA1c<6% (PIO: n=25) vs. conservative glycemic control: titration of OHA to get HbA1c<7% (CONTROL: n=25). Intravascular ultrasound (IVUS) was performed immediately after PCI and repeated at 6 months to determine the effect on instent neointimal plaque volume and area. Coronary stenting was carried out in a standard fashion, with routine use of a glycoprotein 2b/3a inhibitor during the procedure. From August 2002 until June 2005, DES were not permitted in the protocol. After June 2005, we amended the protocol to allow DES, as they had become routinely used in diabetic patients in our institution, especially for vessel size <3mm and/or lesion length>15mm. DES were used in 7 PIO and 11 CONTROL subjects, and bare metal stents (BMS) in the rest. Patients were then followed with clinic visits at 1, 3 and 6 months. OHA, other than pioglitazone, were adjusted in a stepwise manner in order to attain the HbA1c targets. Other concomitant medications, including anti-anginals, lipid-lowering therapy, and antihypertensive medication were adjusted according to their clinical need and current Canadian guidelines. After 6 months treatment, or before if clinically indicated, all subjects were to return for repeat cardiac catheterization, including repeat coronary angiography and IVUS of the intervened vessel to assess the serial change in luminal dimensions. Fasting blood was collected for plasma glucose, HbA1c, insulin, lipid profile, hs-CRP, adiponectin, leptin, matrix metalloproteinase-9, and interleukin-6 at the time of PCI and at the follow-up IVUS. If the patient developed recurrent ischemic symptoms before 6 months, the final IVUS could be performed earlier, if they were found to have clinically-significant restenosis (diameter stenosis > 50%). Otherwise, patients were still encouraged to have their protocol 6 month IVUS follow-up. 41 patients (n=20 PIO, n=21 CONTROL) had analyzable pairs of IVUS.

Study hypothesis: We hypothesized that there would be significantly less instent neointimal proliferation on IVUS at 6 months in the group receiving aggressive glycemic control plus the thiazolidinedione pioglitazone. We also hypothesized that the reduction in neointimal hyperplasia will likely relate to improvements in glycemic control (HbA1c) and insulin resistance. Additionally, we wanted to explore the biochemical predictors (glucose parameters, lipids, inflammatory markers, adipokines) for neointimal proliferation.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 4

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

  • Canada
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 3A7
        • Queen Elizabeth II Health Sciences Centre

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

30 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • between the ages 30 to 80 years
  • had type 2 diabetes mellitus treated with diet or oral hypoglycemic agents (OHA: sulfonylurea or metformin alone or the combination of sulfonylurea or metformin as long as metformin dose was < 2000 mg/d)
  • All patients were undergoing either elective or urgent PCI of a de novo native coronary lesion (> 70 % diameter stenosis) in a vessel ≥ 2.5 mm diameter that was felt to be suitable for stenting and an IVUS examination.

Exclusion Criteria:

  • left main > 50 % stenosis
  • ongoing congestive heart failure or left ventricular ejection fraction < 30%
  • primary PCI for ST elevation MI
  • use of insulin or thiazolidinedione therapy (rosiglitazone or pioglitazone) immediately before PCI
  • known intolerance to thiazolidinediones
  • creatinine > 130 µmol/L
  • significant liver disease: ALT or AST > 3 times upper limit of normal, history of cirrhosis, or hepatitis
  • women who were pregnant, breastfeeding, or childbearing potential

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intensive glycemic control
Included routine use of pioglitazone (30 mg/d) for 6 months in addition to titration of their other oral hypoglycemic agents in order to get the HbA1c<6%.
Drug: pioglitazone
pioglitazone 30mg p.o. once a day for 6 months
Drug: oral hypoglycemic agents
sulfonylurea or metformin
Active Comparator: conservative glycemic control
Included titration of oral hypoglycemic agents to get HbA1c<7% without the use of a thiazolidinedione.
Drug: oral hypoglycemic agents
sulfonylurea or metformin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary IVUS endpoint of the study was the change in three-dimensional neointimal plaque volume within the stented segment at follow-up, compared to baseline.
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
The secondary IVUS endpoint was the change in the two-dimensional NIA within the stent, using the cross-sectional slice showing the smallest LA on follow-up and comparing it to the corresponding baseline slice.
Time Frame: 6 months
6 months

Collaborators and Investigators

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

Sponsor

Queen Elizabeth II Health Sciences Centre

Collaborators

Nova Scotia Health Research Foundation

Investigators

  • Principal Investigator: Lawrence M Title, MD FRCPC, QE II Health Sciences Centre

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

August 1, 2002

Primary Completion (Actual)

November 1, 2006

Study Completion (Actual)

March 1, 2007

Study Registration Dates

First Submitted

January 6, 2009

First Submitted That Met QC Criteria

January 6, 2009

First Posted (Estimate)

January 8, 2009

Study Record Updates

Last Update Posted (Estimate)

January 8, 2009

Last Update Submitted That Met QC Criteria

January 6, 2009

Last Verified

January 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NSHRF #404N-01
  • NSHRF grant #404N-01

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.

Clinical Trials on Coronary Artery Disease

Clinical Trials on pioglitazone

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Venezuela

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe