Peroxisome Proliferator-Activated Receptor-Gamma Activation in Peritoneal Dialysis Patients (PPAR)

The University of Hong Kong (HKU)

Status and phase

Completed

Phase 4

Conditions

End-stage Renal Disease

Treatments

Drug: Pioglitazone

Drug: placebo comparator

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00745225

A111-101

Details and patient eligibility

About

To study whether peroxisome proliferator-activated receptor-gamma activation in peritoneal dialysis patients will reduce inflammation, atherosclerosis, calcification and improve survival of peritoneal dialysis patients

Full description

Peritoneal dialysis patients are at increased risk of cardiovascular morbidity and mortality and are related to the presence of accelerated atherosclerosis. Other than the traditional cardiovascular risk factors, there is increasing evidence that inflammation is associated with the development of atherosclerosis and cardiovascular events in both the general and dialysis population. C-reactive protein is predictive of higher all-cause mortality and cardiovascular mortality, independent of other cardiovascular risk factors and atherosclerotic vascular disease. As a considerable proportion of peritoneal dialysis patients showed elevated C-reactive protein, it raises an important question as to whether lowering C-reactive protein will have any cardiovascular and survival benefit in these patients. On the other hand, insulin resistance with associated hyperinsulinemia is frequently observed in chronic renal failure and dialysis patients. Although the exact mechanism of insulin resistance needs further evaluation, studies indicated that insulin resistance is an important cardiovascular risk factor and outcome predictor in the general and dialysis population. Moreover, recent evidence indicates an association between chronic inflammation and insulin resistance although the exact interrelationship remains unclear. The peroxisome proliferator-activated receptor-gamma (PPAR-g) is a member of the nuclear receptor family of ligand-dependent transcription factors. PPAR-g is highly expressed in adipose tissue and clinical study has confirmed efficacy of the specific ligands for PPAR-gamma, namely thiazolidinediones (TZD), in improving insulin sensitivity. Recent experimental and clinical studies demonstrated that TZD has anti-inflammatory and anti-atherosclerotic properties other than insulin sensitizing effect in type 2 diabetics. We hypothesize that modulation of the PPAR-g activity may be a novel therapeutic strategy for reducing inflammation and improving insulin sensitivity and may retard the progression of atherosclerosis and possibly reduce mortality of our peritoneal dialysis patients.

Enrollment

160 patients

Sex

All

Ages

20 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Both prevalent patients or patients newly started on continuous peritoneal dialysis, with or without diabetes mellitus will be considered eligible for study entry.
For patients newly started on chronic peritoneal dialysis, they will be suitable for recruitment into the study after one month on peritoneal dialysis.
Patients who provide informed consent for the study

Exclusion criteria

Patients with underlying active malignancy
Patients with chronic liver disease or liver cirrhosis
Patients with active infections
Patients with other chronic active inflammatory disease such as systemic lupus erythematosus, rheumatoid arthritis
Patients who refuse study participation
Patients with underlying congenital heart disease or rheumatic heart disease
Patients with poor general condition
Patients with plans for living related kidney transplant within 2 years
Female patients with pregnancy
Patients with history of recurrent hypoglycemia
Patients with Class III and IV congestive heart failure
Patients already receiving glitazones treatment at the screening visit