Effect of Adipokines in Hemodialysis Patients

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Drug: Pioglitazone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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End stage renal disease, Hemodialysis, Pioglitazone, Adipokines