brain activation and satiety in children 2

Conditions: Childhood Obesity

Summary: childhood obesity and related long-term effects are serious public health problems, but not all children with obesity do well in treatment. this study will test a new combination of family-based behavioral treatment (fbt) with a drug intervention using a glucagon-like peptide-1 receptor agonist (glp-1ra) exenatide once weekly extended-release (exqw, bydureon®) in order to improve obesity intervention outcomes in 10-12-year-old children.

using functional and structural magnetic resonance neuroimaging, this study will evaluate brain factors which could undermine treatment responses and long-term obesity intervention outcomes. specific aim 1 will test the effect of adding exqw to fbt on change in bmi z-score over a total glp-1ra treatment duration of 24 weeks and a subsequent 1-year observational follow-up period after treatment cessation. to provide mechanistic insight, specific aim 2 will test whether adding glp-1ra intervention to fbt impacts neural activation by food cues. finally, the proposed research will investigate the role of a cellular inflammatory process in the mediobasal hypothalamus-called gliosis-which might contribute to impaired hypothalamic function, attenuated satiety responsiveness, and potentially to worse weight management outcomes. specific aim 3 will test if hypothalamic gliosis is modified by fbt and/or fbt plus glp-1ra in children and if its extent is related to immediate and/or long-term intervention outcomes. study design: this double-blinded, randomized, placebo-controlled research study uses fmri to characterize neural responses to a test meal before and at the end of fbt intervention, with vs. without additional glp-1ra intervention. in addition, it uses structural mri (smri) to test if mbh gliosis is reversible and/or associated with intervention outcomes.

Eligibility criteria:
inclusion criteria: * 10-12 years of age * male or female * ability and willingness to participate in study visits including fmri scans, blood draws, and weekly injections; * parent willing to provide informed written consent and child willing to provide written assent; * child has bmi z-score \>95th percentile. for age and sex; * one parent that is obese or overweight (bmi \>27 kg/m2); willingness of 1 parent (does not have to be the parent with obesity) to engage in weekly family-based weight control treatment delivered in english. exclusion criteria: * history of acute or chronic serious medical conditions; * known diabetes mellitus or recent (6 mo.) history of anemia; * presence of any implanted metal or metal devices, including ferro-metallic surgical clips or orthodontic braces; * claustrophobia; * documented cognitive disorder, disruptive behavior, inability to participate in group sessions; * current use of medications known to alter appetite, body weight, or brain response * food intolerance to test meal (macaroni and cheese) or vegetarianism/veganism or severe food allergies. * known renal impairment (gfr\<60 ml/min/1.73m2) * history of gastroparesis, pancreatitis or gallstones (unless status post cholecystectomy); * family history of multiple endocrine neoplasia type 2 or familial medullary thyroid carcinoma; * known elevated calcitonin level at phone screening or increased measured calcitonin level at study visits; * untreated thyroid disorder or adrenal insufficiency; * use of weight loss medications (child participant) within 3 months of screening visit. * participating parent is pregnant