Pioglitazone Attenuates Dysmetabolism in Peritoneal Dialysis (PD) Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01258322
Recruitment Status : Completed
First Posted : December 10, 2010
Last Update Posted : December 10, 2010
Baxter Healthcare Corporation
Information provided by:
Huashan Hospital

Brief Summary:
  1. Background:Cardiovascular disease (CVD) is the major cause of mortality in peritoneal dialysis (PD) patients, in whom it is partly attributable to a higher prevalence of dysmetabolism. Currently, few treatments are available with a proven effect on dyslipidemia, insulin resistance and inflammation in this patient group.
  2. Study design: Randomized, cross-over trial.
  3. Settings and Participants: Prevalent PD patients (>20 years old, s-triglycerides >1.8 mmol/L) who had never received glitazones were enrolled.
  4. Interventions: Participants were randomized to receive either oral pioglitazone (PIO; 15 mg once daily) and no pioglitazone, both for 12 weeks and in random order, with a four-week wash out in between.
  5. Outcomes and measurements: The primary endpoint was change of serum triglyceride (TG) level during the PIO as compared to no PIO. Secondary endpoints included changes in other lipid levels, HOMA-IR, adipocytokines and CRP. Outcome effects were assessed using a GLM.

Condition or disease Intervention/treatment Phase
Peritoneal Dialysis Pioglitazone Hypertriglyceridemia Insulin Resistance Inflammation Drug: Pioglitazone Not Applicable

Detailed Description:

Cardiovascular disease (CVD) is the major cause of mortality in chronic kidney disease, including peritoneal dialysis (PD) patients. While survival has not been shown to differ between peritoneal and hemodialysis, because of glucose uptake from the dialysate PD patients are more prone to dyslipidemia, insulin resistance (IR) and obesity. These metabolic disorders are substantially linked to the development of CVD and mortality in this patient population.

Hypertriglyceridemia, reported to be present in 70% of PD patients, is linked to both glucose uptake from the peritoneum and IRand promote vascular damage. Inflammation has been proposed to be a fundamental promoter of atherosclerosis and demonstrated a dose-response relationship between C-reactive protein (CRP) and mortality . Adipocytokines, such as adiponectin,leptin and resistin, also play important roles in the development of dyslipidemia, IR, atherosclerosis, inflammation and CVD in PD patients. Therefore, therapies targeted at metabolic disorder are an important component of treatment for PD patients. Fibrates, peroxisome proliferator-activated receptors (PPAR)-α agonist, can lower serum TG, however, its use in PD patients is limited by its limited efficacy and often-appeared adverse effects such as rhabdomyolysis and hepatic impairment. Nowadays, PPAR-γ agonist, thiazolidinediones (TZDs), represented by pioglitazone and rosiglitazone, exert their hypoglycemic properties through reduction of insulin resistance. For more than ten years, they have been used to control blood glucose in type 2 diabetes mellitus (T2DM). In addition, TZDs have also been noted to have beneficial effects on lipid metabolism and inflammation apart from their effects on glycogenic control. However, the study about TZDs in the treatment of metabolic disorder in PD patients, especially in nondiabetic subjects is very scarce and limited.

We, therefore set out to investigate the effect of TZDs, pioglitazone on hyperlipidemia, insulin resistance, inflammation and adipokine dysmetabolism of PD patients, especially in nondiabetic patients.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Twelve Weeks of Pioglitazone Therapy Significantly Attenuates Dysmetabolism and Reduces Inflammation in Prevalent Peritoneal Dialysis Patients. A Randomized, Cross-over Trial.
Study Start Date : January 2008
Actual Primary Completion Date : September 2008
Actual Study Completion Date : September 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: pioglitazone Drug: Pioglitazone
The patients were randomized divided into 2 groups; one received no pioglitazone for lowing triglyceride, one with oral pioglitazone (Actos®, Takeda®) 15mg once daily for 12 weeks. After a four-week wash out, patients then continued with the alternate therapy.
Other Name: pioglitazone (Actos®, Takeda®) 15mg

Primary Outcome Measures :
  1. change of serum TG level [ Time Frame: 12 weeks ]

Secondary Outcome Measures :
  1. the change of serum CHO, LDL. HDL level, HOMA-IR, adipocytokines level and CRP [ Time Frame: 12 weeks ]

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

All patients received more than one month regular continuous ambulatory peritoneal dialysis(CAPD) or intermittent peritoneal dialysis(IPD). The causes of chronic renal failure were diabetes and non-diabetes.-

Exclusion Criteria:

history of allergy to thiazolidinediones and fenofibrate; history of any sever adverse event for fibrate that can't be tolerated by the patients; patient can not be follow-up regularly; history of myocardial infarction(MI) or coronary artery bypass graft (CABG) surgery within the past 1 month, history of cerebral vascular accident (CVA) or percutaneous transluminal coronary angioplasty(PTCA) within the past 6 months; chronic use of non-steroidal anti-inflammatory drugs(NSAIDs), steroids or immunosuppressives; patient with the acute infection; patient with malignant tumor; have the evidence of severe hepatic injury (ALT/AST>100u/L).-

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01258322

Sponsors and Collaborators
Huashan Hospital
Baxter Healthcare Corporation
Principal Investigator: Tongying Zhu, MD and PhD Huashan Hospital

Responsible Party: Dr. Tongying Zhu, Huashan Hospital Identifier: NCT01258322     History of Changes
Other Study ID Numbers: Neph-1000
First Posted: December 10, 2010    Key Record Dates
Last Update Posted: December 10, 2010
Last Verified: March 2007

Additional relevant MeSH terms:
Insulin Resistance
Pathologic Processes
Glucose Metabolism Disorders
Metabolic Diseases
Lipid Metabolism Disorders
Hypoglycemic Agents
Physiological Effects of Drugs