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GLP-1 Therapy for Weight Loss and Improved Glucose Tolerance in Obese Children

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT00886626
First received: April 22, 2009
Last updated: October 22, 2012
Last verified: October 2012
  Purpose

The prevalence of severely obese children is on the rise. Behavioral therapies for weight loss are successful in some, but others need more aggressive approaches such as drug therapy. In addition, up to 25% of severely obese children have impaired glucose tolerance (IGT), which places them at significantly elevated risk of developing type 2 diabetes mellitus and cardiovascular disease. Although various drug therapies for weight loss and IGT have been explored in adults, few have been evaluated in children.

Recently, a new drug class has emerged that targets deficiencies of GLP-1. One of the main glycemic mechanisms of action of the GLP-1 agonists such as exenatide is to enhance glucose disposal in the postprandial setting and improve glucose tolerance. In addition, exenatide can induce weight loss by decreasing appetite and slowing gastric motility.


Condition Intervention Phase
Obesity, Morbid
Drug: Exenatide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: GLP-1 Therapy for Weight Loss and Improved Glucose Tolerance in Obese Children: A Randomized, Controlled, Pilot Study

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • Change in Body Mass Index (BMI) [ Time Frame: 3-month ] [ Designated as safety issue: No ]
    Change in body mass index (BMI) over three months


Enrollment: 12
Study Start Date: May 2009
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exenatide
Exenatide
Drug: Exenatide
Exenatide, subcutaneous injection, 10 mcg, twice per day
Other Name: Byetta
No Intervention: Control
Control - no intervention

Detailed Description:

This will be a randomized, open-label, controlled, crossover clinical trial in 12 patients. All patients will receive exenatide and undergo the control phase. Following baseline testing, participants will be randomly assigned to treatment order: therapy (exenatide) or control (lifestyle modification). Half (n = 6) will receive exenatide first (3-months) then cross over to control (no drug therapy for 3-months). Half (n = 6) will be assigned to control first (3-months) then cross over to exenatide (3-months). All efforts will be made to stratify randomization based on gender of the participants. Treatment and control conditions will be three months each. Because of the route of administration of exenatide (subcutaneous injection), placebo will not be utilized for the control phase of the study.

Participants in this study will engage in background intensive lifestyle modification offered by the University of Minnesota Pediatric Weight Management Clinic for the entire study, even during the active drug treatment phase. Intensive lifestyle modification will be purely clinical in nature in which children and their families receive continuing counseling from a team of trained professionals including physicians, dieticians, and psychologists to reduce weight by making healthier eating choices and increasing physical activity.

The screening visit will take place in the Pediatric Weight Management Clinic and will include a complete medical history and physical examination. Screening will include review of medical records for previous clinical and laboratory data (including clinically-ordered glucose tolerance test results). All research testing will take place in the University of Minnesota General Clinical Research Center (GCRC). Subjects will undergo testing at the following intervals: baseline, immediately after the first 3-month phase (whether exenatide or control), and immediately after the second 3- month phase (whether exenatide or control). The following measures will be collected after the subject has been fasting for at least twelve hours:

  • Height, weight, body mass index, waist and hip circumference
  • Fat and lean mass (dual energy x-ray absorptiometry: DXA)
  • Tanner stage determination (performed during screening physical exam or may be obtained from medical chart)
  • Fasting lipid profile (total-, LDL-, and HDL-cholesterol, triglycerides)
  • Systolic and diastolic blood pressure
  • Oral glucose tolerance test (glucose and insulin measured every 30 minutes for 2 hours)
  • Endothelial function (digital reactive hyperemia: EndoPAT 2000, Itamar Medical) - in addition to the baseline measure, endothelial function testing will occur at hours one and two of the oral glucose tolerance test
  • Frozen plasma for storage - in addition to the baseline blood draw, blood for endothelial biomarkers will be obtained at hours one and two of the oral glucose tolerance test
  • Arterial stiffness (pulse wave velocity; augmentation index: Sphygmocor, AtCor Medical)
  • Frozen plasma for pharmacokinetic determination of exenatide in children
  Eligibility

Ages Eligible for Study:   8 Years to 19 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 8-19 years old
  • Subject able to give assent, and parent/guardian capable of giving consent on behalf of the child
  • Body mass index (BMI) ≥ 99th percentile (based on gender and age)

Exclusion Criteria:

  • Type 1 or 2 diabetes mellitus
  • Initiation of 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
  • Severe renal impairment (defined as creatinine clearance <30 mL/min)
  • Gastrointestinal disease
  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: NCT00886626

Locations
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Investigators
Principal Investigator: Aaron S. Kelly, Ph.D. University of Minnesota - Clinical and Translational Science Institute
  More Information

No publications provided by University of Minnesota - Clinical and Translational Science Institute

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT00886626     History of Changes
Other Study ID Numbers: 0902M59181
Study First Received: April 22, 2009
Results First Received: April 25, 2012
Last Updated: October 22, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
Obesity
Impaired Glucose Tolerance
Children

Additional relevant MeSH terms:
Obesity
Obesity, Morbid
Weight Loss
Body Weight
Body Weight Changes
Nutrition Disorders
Overnutrition
Overweight
Signs and Symptoms
Exenatide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014