Peroxisome Proliferator-Activated Receptor-Gamma Activation in Peritoneal Dialysis Patients

NCT ID: NCT00745225

Last Updated: 2021-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-02-28
• Study Completion Date: 2014-12-31

Brief Summary

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

Detailed 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.

Conditions

End-stage Renal Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active intervention arm

Peroxisome proliferator activator receptor gamma treatment, Pioglitazone

Group Type: EXPERIMENTAL

Pioglitazone

Intervention Type: DRUG

pioglitazone 15mg daily for 12 weeks, then 30mg daily for 84 weeks

placebo pill

placebo comparator

Group Type: PLACEBO_COMPARATOR

placebo comparator

Intervention Type: DRUG

1 capsule daily, 96 weeks.

Interventions

Pioglitazone

pioglitazone 15mg daily for 12 weeks, then 30mg daily for 84 weeks

Intervention Type: DRUG

placebo comparator

1 capsule daily, 96 weeks.

Intervention Type: DRUG

Other Intervention Names

Actos; Placebo

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baxter Healthcare Corporation

INDUSTRY

Sponsor Role: collaborator

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Dr. Angela Yee-Moon Wang

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Angela YM Wang, MD, PhD, FRCP

Role: PRINCIPAL_INVESTIGATOR

University of Hong Kong, Queen Mary Hospital

Locations

Queen Mary Hospital, Tung Wah Hospital

Hong Kong, , Hong Kong

Countries

Hong Kong

Other Identifiers

A111-101

Identifier Type: -

Identifier Source: org_study_id