Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma) Agonist in Diabetic End-Stage Renal Disease Patients

Study Overview
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Brief Summary
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To test the hypothesis that PPAR-gamma agonist, rosiglitazone, induces carotid plaque regression in diabetic ESRD patients on maintenance PD via its anti-inflammatory property.

Detailed Description
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End-stage renal disease (ESRD) patients are at an increased risk of accelerated atherosclerosis and cardiovascular morbidity and mortality. Non-traditional risk factors such as inflammation and insulin resistance have important contributions to accelerated atherosclerosis in ESRD patients receiving long-term peritoneal dialysis (PD). The peroxisome proliferator-activated receptor-g (PPAR-g) is a member of the nuclear receptor family of ligand-dependent transcription factors. Activation of the PPAR-g has been shown in both clinical and experimental studies to have anti-inflammatory and anti-atherosclerotic properties other than insulin-sensitizing effects. Recent study also showed that PPAR-g agonists reduce plaque inflammation by inhibiting the activation of proinflammatory genes responsible for plaque development and growth. Hence, this study aims to examine the effects of PPAR-g activation on the progression of carotid plaque in diabetic ESRD patients receiving long-term PD using high-resolution magnetic resonance imaging (MRI).

Official Title
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A Randomized Placebo-Controlled Study to Evaluate the Efficacy of Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma) Agonist in Inducing Carotid Atherosclerotic Plaque Regression in Diabetic End-Stage Renal Disease Patients

Conditions
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Endstage Renal Disease, Diabetes

Intervention / Treatment
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* Drug: Pioglitazone
* Drug: Placebo comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diabetic ESRD patients receiving long-term PD treatment, with carotid plaque (defined as focal intima-media thickening >1mm) present on screening ultrasonography Patients who provide informed consent for the study Exclusion Criteria: Patients with systemic inflammatory disease such as systemic lupus erythematosus Patients with chronic liver disease or cirrhosis Patients with current active malignancy Patients with chronic rheumatic heart disease or congenital heart disease Patients with poor general condition Patients with plan for living related kidney transplant within coming 1 year Patients with pre-existing class III/IV heart failure, Patients with recurrent hypoglycemia Patients already on glitazone treatment Female patients with pregnancy Patients with contraindications for MRI examination including those with pacemaker or metallic implant.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Pioglitazone drug 15mg daily for 3 months then 30mg for 9 months (Peroxisome Proliferator-Activated Receptor-gamma agonist) | Drug: Pioglitazone<br>* oral Pioglitazone 15mg daily for 12 weeks, then 30mg daily for 36 weeks<br>* Other names: Actos;|
| Placebo Comparator: 2<br>placebo comparator drug 15mg daily for 3months, then 30mg for 9 months | Drug: Placebo comparator<br>* Placebo comparator<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in carotid plaque volume |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in inflammatory markers include C-reactive protein, interleukin-6, adiponectin, metalloproteinases |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PPAR-gamma, diabetic, kidney disease, atherosclerosis