Brain Systems and Behaviors Underlying Response to Obesity Treatment in Children
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 63
- 试验地点
- 1
- 主要终点
- Change of BMI z-score
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 10 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Exenatide once weekly extended-release
Weekly subcutaneous injections of glucagon-like peptide (GLP)-1 agonist exenatide once weekly extended-release (2mg) for 24 weeks in randomized intervention.
干预措施: Family Based Behavioral Treatment (Behavioral)
Exenatide once weekly extended-release
Weekly subcutaneous injections of glucagon-like peptide (GLP)-1 agonist exenatide once weekly extended-release (2mg) for 24 weeks in randomized intervention.
干预措施: Exenatide 2 mg [Bydureon] (Drug)
Matching placebo
Weekly subcutaneous injections of placebo for 24 weeks.
干预措施: Family Based Behavioral Treatment (Behavioral)
Matching placebo
Weekly subcutaneous injections of placebo for 24 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change of BMI z-score
时间窗: 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
Body mass index (BMI) z-scores will be derived using CDC growth charts, using the LMS method, to allow for comparison of adiposity over time and across children who differ in age and sex.
次要结局
- Meal induced chances in brain activation to visual food cues(Change from Baseline to post-Family Based Behavioral Treatment at week 24)
- BMI z-score(Up to 12-months after ending treatment)
- Indices of metabolic syndrome(Change from Baseline to post-Family Based Behavioral Treatment at week 24)
- Body composition(Change from Baseline to post-Family Based Behavioral Treatment at week 24 and post drug-treatment at week 32)
研究者
Christian L Roth, MD
Professor
Seattle Children's Hospital