Clinical trial NCT04520490: Brain Activation and Satiety in Children 2
Official title: Brain Systems and Behaviors Underlying Response to Obesity Treatment in Children
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Childhood Obesity
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
Collaborators: name: University of Washington
First posted: 2020-08-20
Enrollment: 63
Sex: ALL
Minimum age (years): 10
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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

Primary outcomes:
measure: Change of BMI z-score
timeFrame: Change from drug treatment randomization at week 8 of family-based behavioral treatment (FBT) to end of combined intervention (FBT + drug) at week 24 of FBT
Secondary outcomes:
measure: BMI z-score
timeFrame: Up to 12-months after ending treatment
measure: Body composition
timeFrame: Change from Baseline to post-Family Based Behavioral Treatment at week 24 and post drug-treatment at week 32
measure: Indices of metabolic syndrome
timeFrame: Change from Baseline to post-Family Based Behavioral Treatment at week 24
measure: Meal induced chances in brain activation to visual food cues
timeFrame: Change from Baseline to post-Family Based Behavioral Treatment at week 24
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
References: