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Principal Investigator: Amy C. Gross
Organization: UNIVERSITY OF MINNESOTA
Fiscal Year: 2024
Award: $357,024
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
Project Summary/Abstract
Neurobehavioral characteristics have the potential to predict initial weight loss and weight loss maintenance in
response to various treatment approaches in adolescents with obesity. However, prior research is limited by
heavy reliance on cross-sectional analyses and a focus on immersion-type interventions (e.g., inpatient
treatment), which are not widely available. Identifying neurobehavioral predictors of response to clinically
applicable treatments will stimulate needed progress in the emerging field of precision medicine. Building on a
funded, randomized comparative effectiveness trial (R01-DK123273), the current study will prospectively
examine neurobehavioral predictors of initial weight loss response and weight loss maintenance for
adolescents with obesity participating in intensive lifestyle modification therapy (LMT) or low intensity LMT plus
medical management using the glucagon-like peptide-1 receptor agonist (GLP1-RA), semaglutide. In the
proposed study we will: 1) identify baseline neurobehavioral predictors of weight loss response in adolescents
with obesity undergoing intervention; 2) for participants achieving >5% BMI reduction at 6 months (i.e. initial
responders), identify neurobehavioral predictors of weight loss maintenance at 12; and 3) evaluate differences
in predictors of response between intensive LMT and GLP-1RA therapy. This prospective, observational study
will include 116 adolescents with obesity and will focus on the three main aspects of executive functions -
inhibition, cognitive flexibility, and working memory – as well as reward responsivity using gold-standard
measures. For each domain, a single factor (i.e., score) will be created from factor analysis and these latent
factors will be used as predictors in the statistical models. To our knowledge, this will be the first study to
evaluate neurobehavioral predictors of weight loss response to GLP-1RA therapy in adolescents. Moreover,
we will be one of few who have prospectively evaluated neurobehavioral predictors of treatment response and
weight loss maintenance for adolescents with obesity. Our overarching goal is to move beyond the current
“one-size-fits-all” paradigm and understand how to best match adolescents with obesity to personally effective
treatment, which will maximize clinical outcomes while minimizing exposure to unnecessary risks.
Terms: <12-20 years old><21+ years old><Address><Adolescence><Adolescent><Adolescent Youth><Adolescent obesity><Adult><Adult Human><Affect><Agonist><Appetite><Area><BMI><BMI percentile><BMI z-score><Behavior><Body Weight decreased><Body mass index><Brain><Brain Nervous System><Brain region><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><Characteristics><Childhood><Chronic><Chronic Disease><Chronic Illness><Clinical><Cognitive><Cross Sectional Analysis><Cross-Sectional Analyses><Cross-Sectional Studies><Cross-Sectional Survey><Cues><Data><Desire for food><Development><Disease><Disease Frequency Surveys><Disorder><Drug Therapy><Drugs><Educational workshop><Encephalon><Exposure to><Factor Analyses><Factor Analysis><Food><Foundations><Funding><GLP-1 receptor><GLP-I receptor><Goals><Health><Heterogeneity><Hyperphagia><Immediate Memory><Immersion><Impairment><Individual><Informal Social Control><Inpatients><Intervention><Intervention Strategies><Length of Life><Life Expectancy><Life Style Modification><Longevity><Maintenance><Medical><Medication><NIDDK><NIH><National Institute of Diabetes and Digestive and Kidney Diseases><National Institutes of Health><Neural Development><Obesity><Observation research><Observation study><Observational Study><Observational research><Outcome><Overeating><Parents><Participant><Pharmaceutical Preparations><Pharmacotherapy><Population><Prediction of Response to Therapy><Predictive Factor><Probabilistic Models><Probability Models><Process><Public Health><Quetelet index><Randomized><Research><Resistance><Rewards><Risk><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Self Regulation><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Short-Term Memory><Shortterm Memory><Statistical Models><Time><United States National Institutes of Health><Weight Gain><Weight Increase><Weight Loss><Weight Reduction><Weight maintenance regimen><Workshop><Youth><Youth 10-21><adiposity><adolescence (12-20)><adult adiposity><adult obesity><adulthood><adults with obesity><body weight gain><body weight increase><body weight loss><chronic disorder><clinical applicability><clinical application><clinical care><clinical relevance><clinically relevant><co-morbid><co-morbidity><comorbidity><comparative effectiveness trial><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><corpulence><critical developmental period><developmental><drug treatment><drug/agent><effective intervention><effective therapy><effective treatment><executive control><executive function><experience><flexibility><flexible><glucagon-like peptide-1 receptor><high reward><improved><interventional strategy><juvenile><juvenile human><lifestyle modification><neurobehavioral><neurodevelopment><new approaches><novel approaches><novel strategies><novel strategy><obese adolescents><obesity among adolescents><obesity during adolescence><obesity in adolescence><obesity in adolescents><obesity intervention><obesity therapy><obesity treatment><parent><pediatric><polyphagia><precision medicine><precision-based medicine><predict responsiveness><predict therapeutic response><predict therapy response><predicting response><preference><prospective><public health relevance><randomisation><randomization><randomly assigned><resistant><response><response to therapy><response to treatment><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><standard measure><statistical linear mixed models><statistical linear models><success><therapeutic response><therapy prediction><therapy response><treatment prediction><treatment response><treatment response prediction><treatment responsiveness><treatment strategy><virtual><weight control><weight management><working memory><wt gain><wt-loss><youth adiposity>