Clinical trial NCT01301027: Effect of Adipokines in Hemodialysis Patients
Official title: Effects of Pioglitazone on Adiponectin and Inflammatory Markers in Overweight or Obese Hemodialysis Patients: A Double-Blinded Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: End Stage Renal Disease
Keywords: End stage renal disease
Hemodialysis
Pioglitazone
Adipokines
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: University of Colorado, Denver
First posted: 2011-02-23
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in High Molecular Weight Adiponectin (HMW-A) Concentration in Plasma From Baseline to 6 Months
timeFrame: Baseline and 6 months
measure: Change in High Sensitivity C-Reactive Protein (hsCRP) Concentration in Plasma From Baseline to 6 Months
timeFrame: Baseline and 6 months
Secondary outcomes:
measure: Change in Tumor Necrosis Factor-α (TNF-α) Concentration in Plasma From Baseline to 6 Months
timeFrame: Baseline and 6 months
measure: Change in Interleukin-6 (IL-6) Concentration in Plasma From Baseline to 6 Months
timeFrame: Baseline and 6 months
Other outcomes:
Locations:
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Utah
name: Srinivasan Beddhu, M.D.
role: PRINCIPAL_INVESTIGATOR
References: