Obesity
Conditions
Brief summary
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
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.
Interventions
DRUGExenatide
Exenatide 5 micrograms (mcg) twice per day (BID) for one month; up-titrated to 10 mcg twice per day for remainder of study.
DRUGPlacebo
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).
Sponsors
Children's Hospitals and Clinics of Minnesota
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 19 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Body Mass Index at 3-months | Baseline and 3-months | As results are measured by BMI reduction, percent change (reduction) in BMI is primary outcome measure. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the University of Minnesota, Amplatz Children's Hospital Pediatric Weight Management Clinic in Minneapolis or the McNeely Pediatric Diabetes Center and Endocrinology Clinic, Children's Hospitals and Clinics of Minnesota in St Paul.
Participants by arm
| Arm | Count |
|---|---|
| Exenatide 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)
Open label Exenatide : Exenatide 5 micrograms (mcg) twice per day (BID) for one month; up-titrated to 10 mcg twice per day for remainder of study. | 13 |
| Placebo Injection 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.
Open label Exenatide : Exenatide 5 micrograms (mcg) twice per day (BID) for one month; up-titrated to 10 mcg twice per day for remainder of study. | 13 |
| Total | 26 |
Baseline characteristics
| Characteristic | Placebo Injection | Exenatide | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 13 Participants | 13 Participants | 26 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 15.5 years STANDARD_DEVIATION 1.88 | 14.9 years STANDARD_DEVIATION 1.76 | 15.2 years STANDARD_DEVIATION 1.8 |
| Region of Enrollment United States | 13 participants | 13 participants | 26 participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 13 | 12 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 |
Outcome results
Primary
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.
Time frame: Baseline and 3-months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide | Percent Change From Baseline in Body Mass Index at 3-months | -2.9 percentage of change in BMI | Standard Deviation 1.8 |
| Placebo Injection | Percent Change From Baseline in Body Mass Index at 3-months | -0.15 percentage of change in BMI | Standard Deviation 3.2 |