Effect of Adipokines in Hemodialysis Patients

Not Applicable

Completed

Conditions: End Stage Renal Disease

Interventions: Drug: Placebo
Drug: Pioglitazone

Registration Number: NCT01301027

Lead Sponsor: University of Utah

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 95

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	1 placebo pill a day matching the pioglitazone treatment for 26 weeks
Pioglitazone	Pioglitazone	15 mg/day pioglitazone for 2 weeks, then 30 mg/day for remaining 24 weeks

Primary Outcome Measures

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

Secondary Outcome Measures

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