Brain Activation and Satiety in Children 2 (BASIC2)

• ClinicalTrials.gov Identifier: NCT04520490
• Recruitment Status: Recruiting
• First Posted: August 20, 2020
• Last Update Posted: September 1, 2021
• Sponsor: Seattle Children's Hospital
• Collaborator: University of Washington
• Information provided by (Responsible Party): Christian L Roth, MD, Seattle Children's Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Childhood Obesity	Behavioral: Family Based Behavioral Treatment; Drug: Exenatide 2 mg [Bydureon]; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Brain Systems and Behaviors Underlying Response to Obesity Treatment in Children
• Actual Study Start Date: January 28, 2021
• Estimated Primary Completion Date: November 30, 2023
• Estimated Study Completion Date: August 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 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.	Behavioral: Family Based Behavioral Treatment; Children with obesity accompanied by at least one parent or caregiver will attend 24 weekly sessions. Most sessions will be held via video-conference and include 25-30 min. meetings between an interventionist and each child/parent pair to individualize treatment, followed by separate child and parent group meetings lasting 40 - 45 min. A select few sessions will be held in-person between an interventionist and each child/parent pair with no group session. Parents will serve as primary agents of change for their child and for themselves. Training will focus on food and physical activity education, parenting around food and physical activity, and use of behavioral skills (e.g., self-monitoring, environmental control, contingency management). Intervention groups of 8-12 children/families will be initiated every 3-6 mos. in study yrs. 2-3.; Drug: Exenatide 2 mg [Bydureon]; Weekly injections of active drug.; Other Name: Bydureon®
Placebo Comparator: Matching placebo; Weekly subcutaneous injections of placebo for 24 weeks.	Behavioral: Family Based Behavioral Treatment; Children with obesity accompanied by at least one parent or caregiver will attend 24 weekly sessions. Most sessions will be held via video-conference and include 25-30 min. meetings between an interventionist and each child/parent pair to individualize treatment, followed by separate child and parent group meetings lasting 40 - 45 min. A select few sessions will be held in-person between an interventionist and each child/parent pair with no group session. Parents will serve as primary agents of change for their child and for themselves. Training will focus on food and physical activity education, parenting around food and physical activity, and use of behavioral skills (e.g., self-monitoring, environmental control, contingency management). Intervention groups of 8-12 children/families will be initiated every 3-6 mos. in study yrs. 2-3.; Drug: Placebo; Weekly placebo injections

Outcome Measures

Primary Outcome Measures :

1. Change of BMI z-score [ Time Frame: 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.

Secondary Outcome Measures :

1. BMI z-score [ Time Frame: Up to 12-months after ending treatment ]
   Change of body mass index (BMI) z-scores 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.
2. Body composition [ Time Frame: Change from Baseline to post-Family Based Behavioral Treatment at week 24 and post drug-treatment at week 32 ]
   Changes in body composition as assessed using a bioelectrical impedance (BIA)
3. Indices of metabolic syndrome [ Time Frame: Change from Baseline to post-Family Based Behavioral Treatment at week 24 ]
   Changes of insulin resistance assessed by fasting insulin used for homeostasis model assessment of insulin resistance (HOMA-IR) using the formula insulin [mU/l] x glucose [mmol/l]) / 22.5
4. Meal induced chances in brain activation to visual food cues [ Time Frame: Change from Baseline to post-Family Based Behavioral Treatment at week 24 ]
   Change of brain response to visual food cues measured by functional magnetic resonance imaging in a priori regions of interest

Eligibility Criteria

• Ages Eligible for Study: 10 Years to 12 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Christian L Roth, MD; 206-987-5428; christian.roth@seattlechildrens.org

Contact: Clinton T Elfers; 206-884-1256; clinton.elfers@seattlechildrens.org

Locations

United States, Washington

Seattle Children's Hospital; Recruiting

Seattle, Washington, United States, 98105

Contact: Clinton T Elfers 206-884-1256 clinton.elfers@seattlechildrens.org

Principal Investigator: Christian L Roth, MD

Sponsors and Collaborators

Seattle Children's Hospital

University of Washington

More Information

• Responsible Party: Christian L Roth, MD, Professor, Seattle Children's Hospital
• ClinicalTrials.gov Identifier: NCT04520490
• Other Study ID Numbers: STUDY00001984
• First Posted: August 20, 2020
• Last Update Posted: September 1, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Obesity; Pediatric Obesity; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Exenatide; Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Obesity Agents; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists