A randomised, placebo-controlled trial of the effect of pioglitazone on vascular endothelial function and novel biomarkers for macrovascular events in diabetics with established peripheral arterial disease - PAD and Pioglitazone Study

• Conditions: The study involves patients with type 2 Diabetes and Peripheral Arterial Disease.The overall objective of the research proposal is to determine the occurrence of biomarkers that typify the metabolic syndrome in patients with peripheral vascular diseases.

• Registration Number: EUCTR2007-001800-20-GB
• Lead Sponsor: niversity of Dundee

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-06-26
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

For Pre-Intervention stage of the study subjects with Peripheral Arterial Disease (PAD)and type 2 Diabetes will be included. PAD will be defined as patients with classical symptoms of intermittent claudication plus an ankle brachial blood pressure index (ABPI) of <0.9, the accepted cut off level for such a diagnosis.

We are amending our inclusion criteria and will also be including patients with toe-brachial pressure index (TBI) of <0.70. This measurement will be used in patients who have high ABPI >1.1 due to non-compressible arteries. This validated measurement has previously been used in Genzyme WALK study which is an International Gene Therapy trial in PAD patients. There is no clinical contraindication for these patients. This will help us in recruitment.

We are also submitting a poster about the study which we will display around the hospital for advertisement of the study.

For Intervention stage of the study patients with short distance claudication (<200yards) will be selected for the walking study , as their walking distances are more reproducible, ( ie using the standardized Gardner walking treadmill protocol no more than 25% variation from 2 consecutive treadmill tests performed at least a week apart during the Screening period). Patients for this 2nd study will be type 2 diabetic patients not receiving insulin.
Are the trial subjects under 18?
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Contraindication to thiazolidinedione group of drugs.
2. Subjects taking Sulphonylureas
3. Subjects with Cardiovascular disease event within last three months like MI, unstable angina, stroke.
4. For Phase 2 study, subjects having more than 25% variation from 2 consecutive treadmill tests performed atleast a week apart.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: Pre-Intervention Stage:<br>1.Identify biomarkers for improved vascular health<br>2.Transcriptional mRNA profiling of peripheral blood leukocytes from patients with PAD in reference to standard treatment <br>3.Transcriptional gene and protein profiling in muscle of PAD patients in resting and in exercise <br> <br>Intervention Stage:<br>4.Correlate clinical parameters (e.g. walking distances) in patients with Peripheral Arterial Disease (PAD) and type 2 diabetes treated with various standard of care medicines to genes and protein profiling in muscle biopsies. ;Main Objective: The overall objective of the research proposal is to determine the occurrence of biomarkers with proven links to future Cardiovascular events in patients with Peripheral Arterial Disease (PAD)and type 2 diabetes receiving various standards of care medicines including pioglitazone.;Primary end point(s): New biomarkers in PAD