Effect of Adipokines in Hemodialysis Patients

Effects of Pioglitazone on Adiponectin and Inflammatory Markers in Overweight or Obese Hemodialysis Patients: A Double-Blinded Randomized Controlled Trial

This is a double blinded randomized clinical trial of pioglitazone vs. placebo in overweight or obese, diabetic and non-diabetic hemodialysis patients. This study will examine whether pioglitazone modulates adipokine production by adipose tissue in hemodialysis patients and whether these changes result in reduction of inflammation, insulin resistance and oxidative stress and increase in muscle mass.

In addition, this study will also examine the associations of adiposity with adipokines and the metabolic milieu in hemodialysis patients to better understand the biology of adipocytes in uremic milieu.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Drug: Pioglitazone; Drug: Placebo

Detailed Description

Randomization:

100 overweight or obese patients will be randomly allocated to oral pioglitazone 15 mg/d or placebo for two weeks by blocks of five using a random number generator and monitored for adverse events including hypoglycemia. If they tolerate the 15 mg pioglitazone or matching placebo for two weeks, participants will be assigned to 30 mg of pioglitazone or matching placebo for 24 more weeks. Those who received 15 mg of pioglitazone will receive 30 mg of pioglitazone for the next 24 weeks. Those who received placebo for initial 2 weeks will receive another placebo that matches the 30 mg pioglitazone pill for 24 weeks.

Baseline:

Participants will have fasting blood drawn for adipokines: Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-6 (IL-6), high sensitivity C-Reactive Protein (hsCRP), high molecular weight Adiponectin (HMW-A), and leptin. All patients will undergo MRI scans on the mid-week non-dialysis day. Twenty each of overweight/obese patients randomized to pioglitazone or placebo will also undergo subcutaneous fat biopsy on the mid-week non-dialysis day.

Study Period:

Participants will return to the dialysis unit at weeks 2, 4, 6, 10, 14, 18, 22, and 26. During these visits, clinical assessments will be conducted including review of blood sugars, jaundice, weight gain, and visual symptoms. Study treatment compliance will be assessed and details of adverse events experienced, particularly hospitalizations and emergency department visits will be collected. Fasting blood draws for primary and secondary outcomes will be collected on visit weeks 10 and 26.

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Overweight (Body Mass Index ≥ 25 kilograms per meter squared (kg/m2))
• Adult (18 years or older)
• Chronic hemodialysis patient
• Diabetic (type 2) or insulin resistant

Exclusion Criteria:

• <18 years old
• No insulin resistance
• Active liver disease
• Class III or IV New York Heart Association heart failure
• Macular edema or hard exudates near macula on fundoscopy
• Current active malignancy (excluding squamous and basal cell skin cancers)
• Active AIDS
• Chronic lung disease requiring supplemental oxygen therapy
• Enrolled in interventional trials using drugs or devices
• Bone break of long bones, vertebrae, or hips in the past three years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pioglitazone; 15 mg/day pioglitazone for 2 weeks, then 30 mg/day for remaining 24 weeks	Drug: Pioglitazone; 15mg/day pioglitazone for 2 weeks, then 30mg/day pioglitazone for the remaining 24 weeks; Other Names: Actos
Placebo Comparator: Placebo; 1 placebo pill a day matching the pioglitazone treatment for 26 weeks	Drug: Placebo; 1 pill a day for 26 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in High Molecular Weight Adiponectin (HMW-A) Concentration in Plasma From Baseline to 6 Months	The percent difference in HMW-A concentration geometric mean values from baseline to 6 months was calculated for each arm	Baseline and 6 months
Change in High Sensitivity C-Reactive Protein (hsCRP) Concentration in Plasma From Baseline to 6 Months	The percent difference in hsCRP concentration geometric mean values from baseline to 6 months was calculated for each arm	Baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Tumor Necrosis Factor-α (TNF-α) Concentration in Plasma From Baseline to 6 Months	The percent difference in TNF-α concentration geometric mean values from baseline to 6 months was calculated for each arm	Baseline and 6 months
Change in Interleukin-6 (IL-6) Concentration in Plasma From Baseline to 6 Months	The percent difference in IL-6 concentration geometric mean values from baseline to 6 months was calculated for each arm	Baseline and 6 months

Collaborators and Investigators

• Sponsor: University of Utah
• Collaborators: University of Colorado, Denver; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Srinivasan Beddhu, M.D., University of Utah

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: February 18, 2011
• First Submitted That Met QC Criteria: February 22, 2011
• First Posted (Estimate): February 23, 2011

Study Record Updates

• Last Update Posted (Estimate): October 3, 2016
• Last Update Submitted That Met QC Criteria: August 9, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: End stage renal disease; Adipokines; Hemodialysis; Pioglitazone
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Hypoglycemic Agents; Physiological Effects of Drugs; Pioglitazone
• Other Study ID Numbers: IRB_00028427; R01DK078112 (U.S. NIH Grant/Contract)