Exenatide in Extreme Pediatric Obesity

Study Overview
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Brief Summary
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Extreme pediatric obesity, the fastest growing category of obesity in youth, is associated with high risk for developing cardiovascular disease (CVD) and type 2 diabetes (T2DM). Obesity tracks strongly into adulthood and interventions early in life may reduce risk for developing cardiovascular disease and type 2 diabetes. Few drug therapies for weight loss have been evaluated in adolescents. Since exenatide is associated with weight loss and improves risk factors for cardiovascular disease and type 2 diabetes in adults, it may be useful in extremely obese youth. Our primary objective in this study is to generate preliminary data on the ability of exenatide to reduce body mass index (BMI) and improve risk factors for cardiovascular disease and type 2 diabetes in 26 extremely obese adolescents (age 12-19 years) in a three-month, randomized, double-blind, placebo-controlled pilot clinical trial. GLP-1 therapy has never been evaluated as a treatment for pediatric obesity and is an innovative approach to a challenging and significant health care problem.

Detailed Description
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26 (approximately 13 per site) extremely obese (Body mass index [BMI] > or = 1.2 times the 95th percentile or BMI > or = 35 kg/m2) adolescents (age 12-19 years old) will be enrolled in a six-month study consisting of a three-month, randomized, double-blind (participants and investigators), placebo-controlled pilot clinical trial phase followed by a three-month open-label extension during which all participants will receive exenatide. For the initial three-month phase, participants will be equally (by site) and randomly assigned to one of two groups: 1) exenatide plus lifestyle modification, or 2) placebo plus lifestyle modification. Following baseline testing, subjects will be randomly assigned to study group. Participants will return at one-month for titration and assessment of safety (blood draw and adverse event assessment) and injection/lifestyle modification compliance and at three-months for reassessment of baseline variables and injection/lifestyle modification compliance and allocation to study drug for the three-month open-label extension. Participants will return at four-months for assessment of safety (blood draw and adverse event assessment) and injection/lifestyle modification compliance and at six-months for reassessment of baseline variables and injection/lifestyle modification compliance. All subjects, regardless of group assignment, will participate in the clinical lifestyle modification program offered through either the University of Minnesota or Children's Hospitals and Clinics weight management programs. Participants and their families receive regular (approximately bi-monthly) face-to-face and/or phone behavioral-, dietary-, and physical activity-counseling from a multi-disciplinary team of health care professionals including physicians, dieticians, registered nurses, psychologists, and exercise physiologists. Screening will include review of medical records for previous clinical and laboratory data. The following measures will be collected at baseline, 3 months, and 6 months. Subject will be asked to fast for a minimum of 12 hours.

Official Title
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Exenatide in Extreme Pediatric Obesity

Conditions
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Obesity

Intervention / Treatment
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* Drug: Exenatide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index > or = 1.2 times the 95th percentile (based on gender and age) or Body mass index > or = 35 kg/m2 12-19 years old Exclusion Criteria: Type 1 or 2 diabetes mellitus Previous (within 3-months) or current use of weight loss medication (patients may undergo washout) Previous bariatric surgery Recent initiation (within 1-month) of anti-hypertensive or lipid medication Previous (within 1-month) or current use of medication to treat insulin resistance or hyperglycemia (patients may undergo washout) Major psychiatric disorder Pregnant or planning to become pregnant Tobacco use Liver/renal dysfunction History of pancreatitis Obesity associated with genetic disorder Hyperthyroidism or uncontrolled hypothyroidism Uncontrolled hypertriglyceridemia (=300 mg/dL) Current eating disorder Previous (within 3-months) or current use of drugs associated with weight gain (e.g. steroids/anti-psychotics)

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide, then Open-Label Exenatide<br>Exenatide 5 micrograms (mcg): administered with injection twice per day (BID) for one month; up-titrated to 10 mcg twice per day for remainder of study (5 months) | Drug: Exenatide<br>* Exenatide 5 micrograms (mcg) twice per day (BID) for one month; up-titrated to 10 mcg twice per day for remainder of study.<br>* Other names: Byetta;|
| Placebo Comparator: Placebo, then Open Label Exenatide<br>Placebo injection twice a day for three months; Exenatide open label 5mcg twice a day for one month and up-titrated to 10mcg twice a day for remaining two months of study. | Drug: Exenatide<br>* Exenatide 5 micrograms (mcg) twice per day (BID) for one month; up-titrated to 10 mcg twice per day for remainder of study.<br>* Other names: Byetta;Drug: Placebo<br>* Participants were randomized to a placebo injection for the first three months, then given open-label Exenatide for the remaining three months (Initiated at 5 mcg, twice per day, delivered by subcutaneous injection. After 1 month, exenatide was uptitrated to 10 mcg, twice per day for the remaining 2 months of the drug treatment phase).<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Body Mass Index at 3-months | As results are measured by BMI reduction, percent change (reduction) in BMI is primary outcome measure. | Baseline and 3-months |