Peroxisome Proliferator-Activated Receptor-Gamma Activation in Peritoneal Dialysis Patients
Condition: End-stage Renal Disease
MeSH terms: Kidney Failure, Chronic
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Pioglitazone; placebo comparator
Intervention type(s): Drug; Drug
Intervention description(s): pioglitazone 15mg daily for 12 weeks, then 30mg daily for 84 weeks; 1 capsule daily, 96 weeks.
Other intervention name(s): Actos; Placebo
Intervention MeSH terms: Pioglitazone
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Double-blind randomized placebo-controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: peritoneal dialysis, cardiovascular, PPAR-gamma