Pioglitazone Therapy in Obese Children With Insulin Resistance: A Randomized, Controlled Pilot Study
Primary Purpose
Obesity, Insulin Resistance
Status
Withdrawn
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
pioglitazone
Metformin
Sponsored by
About this trial
This is an interventional treatment trial for Obesity focused on measuring Obese children with insulin resistance
Eligibility Criteria
Inclusion Criteria:
- Age 10-17 years old
- Subject able to give assent, and parent/guardian capable of giving consent on behalf of the child
- Body mass index (BMI) ≥ 95th percentile (based on gender and age)
Fasting insulin ≥ 15 µU/mL AND one or more of the following (cutoffs based on the International Diabetes Federation definition of pediatric metabolic syndrome)1:
- Triglycerides ≥ 150 mg/dL
- HDL cholesterol < 40 mg/dL
- Systolic blood pressure ≥ 130 mmHg
Exclusion Criteria:
- Type 1 or 2 diabetes mellitus
- Has begun a new drug therapy within the past 30 days prior to the screening visit
- BMI ≥ 55
- History of weight loss surgery
- Obesity from a genetic cause (e.g., Prader-Willi)
- Central nervous system injury or severe neurological impairment
- Known systolic or diastolic dysfunction or heart failure
- Females who are currently pregnant or planning to become pregnant
- Liver enzymes > 2.5 times upper limit of normal
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
pioglitazone
Metformin
Arm Description
Pioglitazone: 15 mg per day for 4 weeks, then up-titrated to 30 mg per day for 12 weeks
Metformin XR; 1000 mg once daily for 16 weeks.
Outcomes
Primary Outcome Measures
HDL cholesterol, triglycerides, blood pressure, insulin resistance, endothelial function, arterial stiffness, adipokines, oxidative stress, and blood biomarkers of endothelial activation
Secondary Outcome Measures
Full Information
NCT ID
NCT00775164
First Posted
October 16, 2008
Last Updated
August 30, 2012
Sponsor
University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT00775164
Brief Title
Pioglitazone Therapy in Obese Children With Insulin Resistance: A Randomized, Controlled Pilot Study
Official Title
Pioglitazone Therapy in Obese Children With Insulin Resistance: A Randomized, Controlled Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
August 2012
Overall Recruitment Status
Withdrawn
Why Stopped
Inadequate enrollment
Study Start Date
January 2009 (undefined)
Primary Completion Date
December 2010 (Anticipated)
Study Completion Date
February 2011 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of this study is to examine the effects of four months of pioglitazone vs. metformin treatment on HDL cholesterol, triglycerides, blood pressure, insulin resistance, endothelial function, arterial stiffness, adipokines, oxidative stress, and blood biomarkers of endothelial activation in obese insulin resistant children. 30 obese children with elevated fasting insulin levels will be randomly assigned to pioglitazone or metformin for 16 weeks. Change in clinical variables over the 16-week study period will be compared between groups.
Detailed Description
Background and Specific Aim/Hypothesis Obese, insulin resistant children are at increased risk of future cardiovascular disease due to elevated systolic blood pressure, fasting insulin, triglycerides, inflammation, oxidative stress, and reduced HDL cholesterol. Behavioral/lifestyle therapy should be the foundational approach to treating obesity and insulin resistance in all individuals, especially children. However, some children may need concomitant medical therapy in order to adequately address their severe risk factor profile and early vascular abnormalities. Although not approved by the FDA, metformin has been used with mixed success to treat obesity-associated cardiometabolic risk factors in children with evidence of insulin resistance. Clearly, other drug therapies should be explored to treat cardiovascular risk factors in obese, insulin resistant children.
Thiazolidinediones have been used to improve glucose control in adult patients with type 2 diabetes mellitus for approximately 10 years. These peroxisome proliferator activated receptor agonists are unique among anti-diabetic agents in that they regulate gene transcription to improve insulin sensitivity in peripheral tissues (predominately skeletal muscle and adipose tissue). In addition to improving glycemic control, these drugs also improve multiple cardiometabolic risk factors such as lipoprotein profile, blood pressure, inflammatory markers, adipokines, and endothelial function. Despite the substantial body of data showing benefit in adults, pioglitazone has never been evaluated as a therapy to improve the cardiometabolic risk factor profile in obese children with evidence of insulin resistance.
Specific Aim: To examine the effects of four months of pioglitazone vs. metformin treatment on HDL cholesterol, triglycerides, blood pressure, insulin resistance, endothelial function, arterial stiffness, adipokines, oxidative stress, and blood biomarkers of endothelial activation in obese, insulin resistant children.
Hypothesis: In the context of background behavioral therapy, four months of pioglitazone vs. metformin treatment will significantly improve HDL cholesterol, triglycerides, blood pressure, insulin resistance, endothelial function, arterial stiffness, adipokines, oxidative stress, and blood biomarkers of endothelial activation in obese insulin resistant children.
Significance There is a substantial lack of data in the literature concerning potential drug therapies for reducing risk factors in children at high risk of developing future cardiovascular disease. Since the prevalence of obesity and insulin resistance in children has increased dramatically in the last several decades, there is an urgent need for data from randomized, controlled trials to guide treatment approaches for high risk children. This pilot study will result in the acquisition of valuable preliminary data which will be used to seek funding for and conduct a larger scale clinical trial evaluating the efficacy of pioglitazone for treating cardiometabolic risk factors in obese, insulin resistant children.
Methods Patient Population: 30 obese, hyperinsulinemic children and adolescents entering a Pediatric Weight Management Program at the University of Minnesota will be enrolled. In this program, children and their families work with a team of trained professionals including physicians, dieticians, and psychologists to reduce weight by making healthier eating choices and increasing physical activity.
Study Design: This will be a randomized, double-blind, active-comparator clinical trial. Variables will be assessed at baseline (prior to randomization) and after four months of therapy.
Data Collection: The screening visit will take place in the Pediatric Weight Management Clinic and will include a complete medical history and physical examination. All research testing will take place in the University of Minnesota General Clinical Research Center (GCRC).
Statistical Analysis and Power Considerations: Randomization will be stratified by gender and Tanner stage. Changes between groups over time will be compared with a 2X2 (group by time) repeated measures ANOVA with Bonferroni post-hoc tests. The main analysis of interest will be the ANOVA interaction term, which compares the change in variables over time (pre vs. post) between groups. The purpose of this study will be to obtain preliminary data to design and seek funding for a larger clinical trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Insulin Resistance
Keywords
Obese children with insulin resistance
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
pioglitazone
Arm Type
Experimental
Arm Description
Pioglitazone: 15 mg per day for 4 weeks, then up-titrated to 30 mg per day for 12 weeks
Arm Title
Metformin
Arm Type
Active Comparator
Arm Description
Metformin XR; 1000 mg once daily for 16 weeks.
Intervention Type
Drug
Intervention Name(s)
pioglitazone
Other Intervention Name(s)
ACTOS
Intervention Description
15 mg per day for 4 weeks, then up-titrated to 30 mg per day for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Glucophage XR
Intervention Description
Metformin XR; 1000 mg once daily
Primary Outcome Measure Information:
Title
HDL cholesterol, triglycerides, blood pressure, insulin resistance, endothelial function, arterial stiffness, adipokines, oxidative stress, and blood biomarkers of endothelial activation
Time Frame
16 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 10-17 years old
Subject able to give assent, and parent/guardian capable of giving consent on behalf of the child
Body mass index (BMI) ≥ 95th percentile (based on gender and age)
Fasting insulin ≥ 15 µU/mL AND one or more of the following (cutoffs based on the International Diabetes Federation definition of pediatric metabolic syndrome)1:
Triglycerides ≥ 150 mg/dL
HDL cholesterol < 40 mg/dL
Systolic blood pressure ≥ 130 mmHg
Exclusion Criteria:
Type 1 or 2 diabetes mellitus
Has begun a new drug therapy within the past 30 days prior to the screening visit
BMI ≥ 55
History of weight loss surgery
Obesity from a genetic cause (e.g., Prader-Willi)
Central nervous system injury or severe neurological impairment
Known systolic or diastolic dysfunction or heart failure
Females who are currently pregnant or planning to become pregnant
Liver enzymes > 2.5 times upper limit of normal
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aaron S. Kelly, Ph.D.
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Pioglitazone Therapy in Obese Children With Insulin Resistance: A Randomized, Controlled Pilot Study
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