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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00886626
Recruitment Status : Completed
First Posted : April 23, 2009
Results First Posted : August 17, 2012
Last Update Posted : October 29, 2012
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute

Brief Summary:

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 or disease Intervention/treatment Phase
Obesity, Morbid Drug: Exenatide Phase 2

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (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
Study Start Date : May 2009
Actual Primary Completion Date : February 2011
Actual Study Completion Date : February 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Exenatide
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Exenatide
Drug: Exenatide
Exenatide, subcutaneous injection, 10 mcg, twice per day
Other Name: Byetta
No Intervention: Control
Control - no intervention

Primary Outcome Measures :
  1. Change in Body Mass Index (BMI) [ Time Frame: 3-month ]
    Change in body mass index (BMI) over three months

Information from the National Library of Medicine

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Ages Eligible for Study:   8 Years to 19 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00886626

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

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: University of Minnesota - Clinical and Translational Science Institute Identifier: NCT00886626     History of Changes
Other Study ID Numbers: 0902M59181
First Posted: April 23, 2009    Key Record Dates
Results First Posted: August 17, 2012
Last Update Posted: October 29, 2012
Last Verified: October 2012

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

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