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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Baxter Healthcare Corporation
Information provided by (Responsible Party):
The University of Hong Kong
ClinicalTrials.gov Identifier:
NCT00745225
First received: September 1, 2008
Last updated: June 19, 2013
Last verified: June 2013
  Purpose

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


Condition Intervention Phase
End-stage Renal Disease
Drug: Pioglitazone
Drug: placebo comparator
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Targeting Peroxisome Proliferator-Activated Receptor-Gamma in Peritoneal Dialysis Patients - Will it Reduce Inflammation, Atherosclerosis, Calcification and Improve Survival of Peritoneal Dialysis Patients?

Resource links provided by NLM:


Further study details as provided by The University of Hong Kong:

Primary Outcome Measures:
  • Change in carotid intima-media thickness [ Time Frame: wk 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in endothelial function, carotid plaque, vascular calcium score, arterial stiffening, abdominal visceral fat, C-reactive protein, HOMA, residual renal function, insulin dosage, overall survival and cardiovascular event-free survival [ Time Frame: at wk 24, wk 48 and wk 96 ] [ Designated as safety issue: No ]
  • carotid intima-media thickness [ Time Frame: Wk 24 and wk 96 ] [ Designated as safety issue: No ]

Estimated Enrollment: 160
Study Start Date: February 2006
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active intervention arm
Peroxisome proliferator activator receptor gamma treatment, Pioglitazone
Drug: Pioglitazone
pioglitazone 15mg daily for 12 weeks, then 30mg daily for 84 weeks
Other Name: Actos
Placebo Comparator: placebo pill
placebo comparator
Drug: placebo comparator
1 capsule daily, 96 weeks.

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.

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00745225

Locations
Hong Kong
Queen Mary Hospital, Tung Wah Hospital, Pamela Youde Nethersole Eastern Hospital
Hong Kong, Hong Kong, 0000
Sponsors and Collaborators
The University of Hong Kong
Baxter Healthcare Corporation
Investigators
Principal Investigator: Angela YM Wang, MD, FRCP University of Hong Kong, Queen Mary Hospital
  More Information

No publications provided

Responsible Party: The University of Hong Kong
ClinicalTrials.gov Identifier: NCT00745225     History of Changes
Other Study ID Numbers: A111-101
Study First Received: September 1, 2008
Last Updated: June 19, 2013
Health Authority: Hong Kong: Ethics Committee

Keywords provided by The University of Hong Kong:
peritoneal dialysis, cardiovascular, PPAR-gamma

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014