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Effect of Adipokines in Hemodialysis Patients

This study has been completed.
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Colorado, Denver
Information provided by (Responsible Party):
Srinvasan Beddhu, University of Utah
ClinicalTrials.gov Identifier:
NCT01301027
First received: February 18, 2011
Last updated: August 9, 2016
Last verified: August 2016
  Purpose

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.


Condition Intervention
End Stage Renal Disease
Drug: Pioglitazone
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Pioglitazone on Adiponectin and Inflammatory Markers in Overweight or Obese Hemodialysis Patients: A Double-Blinded Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • Change in High Molecular Weight Adiponectin (HMW-A) Concentration in Plasma From Baseline to 6 Months [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    The percent difference in hsCRP concentration geometric mean values from baseline to 6 months was calculated for each arm


Secondary Outcome Measures:
  • Change in Tumor Necrosis Factor-α (TNF-α) Concentration in Plasma From Baseline to 6 Months [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    The percent difference in IL-6 concentration geometric mean values from baseline to 6 months was calculated for each arm


Enrollment: 95
Study Start Date: May 2008
Study Completion Date: December 2015
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01301027

Locations
United States, Colorado
University of Colorado
Denver, Colorado, United States, 80262
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
University of Utah
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Colorado, Denver
Investigators
Principal Investigator: Srinivasan Beddhu, M.D. University of Utah
  More Information

Responsible Party: Srinvasan Beddhu, MD, Associate Professor of Medicine, University of Utah
ClinicalTrials.gov Identifier: NCT01301027     History of Changes
Other Study ID Numbers: IRB_00028427  R01DK078112 
Study First Received: February 18, 2011
Results First Received: August 9, 2016
Last Updated: August 9, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by University of Utah:
End stage renal disease
Hemodialysis
Pioglitazone
Adipokines

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 09, 2016