Enhancing Weight Loss Maintenance With GLP-1RA (BYDUREON™) in Adolescents With Severe Obesity

Long-term weight loss maintenance is seldom achieved by individuals with obesity owing to numerous biological adaptations involving appetite, satiety, and energy expenditure in the post- weight loss setting. Following a loss in body weight, peripheral and central mechanisms convey a sense that energy reserves have dwindled, activating a strong counter response to increase caloric intake. Adolescents with severe obesity are not immune to the vexing issue of weight regain. Indeed, only 2% are able to achieve and maintain clinically-meaningful weight loss with lifestyle modification therapy. Therefore, novel treatment paradigms focused on long-term weight loss maintenance are urgently needed. Pharmacotherapy has the potential to prevent weight regain by targeting specific counter-regulatory mechanisms in the post- weight loss setting. One of the most promising candidates is the glucagon like peptide-1 receptor agonist (GLP-1RA) class, which greatly enhanced weight loss maintenance following a short-term low calorie diet among adults with obesity. The rationale for focusing on GLP-1RA treatment (BYDUREON™) to prevent weight regain is supported by the multiple central and peripheral mechanisms of action targeted by this class of drug; many of which specifically address the biological adaptations known to induce relapse. The investigators have strong preliminary data demonstrating that GLP-1RA treatment reduces BMI in adolescents with severe obesity. Moreover, the investigators and others have shown that although meal replacement therapy (structured meals of known caloric content) can elicit robust short-term weight loss among adolescents with severe obesity, weight regain is a pervasive problem. Therefore, in this clinical trial, our innovative approach will utilize GLP-1RA treatment to target weight regain following short-term meal replacement therapy in youth with severe obesity. Participants who achieve ≥5% BMI reduction during the meal replacement phase will be randomized to GLP-1RA treatment or placebo for an additional 52 weeks while simultaneously engaging in lifestyle modification therapy. Importantly, this study will also allow us to examine the extent to which GLP-1RA treatment addresses mechanisms of weight regain, investigate other pleiotropic benefits of GLP-1RA, and identify predictors of weight loss response.

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Key information

Conditions

Severe Obesity Body Weight Body Weight Changes Nutrition Disorders Nutritional and Metabolic Diseases Obesity Obesity, Morbid Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms Weight Loss

Age range

12 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

About this study

Primary Objective Evaluate the effect of GLP-1RA treatment on the maintenance of weight loss and durability of cardiometabolic risk factor improvements among adolescents with severe obesity following a meal replacement induction period. The investigators hypothesize that adolescents with severe obesity receiving GLP-1RA treatment following a short-term meal replacement induction period will demonstrate superior maintenance of initial BMI reduction 52 weeks following randomization compared to those assigned to placebo (primary endpoint) and that a higher proportion of those assigned to GLP-1RA treatment vs. placebo will maintain ≥5% BMI reduction from baseline to the 52-week time point (secondary endpoint).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

BMI ≥1.2 times the 95th percentile (based on sex and age) or BMI ≥35 kg/m2
12-17 years old

Exclusion criteria

Type 1 or 2 diabetes mellitus
Previous (within 6 months) or current use of medication(s) prescribed primarily for weight loss (refer to appendix material for comprehensive list)
If currently using weight altering drug(s) for non-obesity indication(s) (refer to appendix material for comprehensive list), any change in drug(s) or dose within the previous 6 months
Previous bariatric surgery
If currently using anti-hypertensive medication(s), lipid medication(s), and/or medication(s) to treat insulin resistance (refer to appendix material for comprehensive list), any change in drug(s) or dose within the previous 6 months
If currently using CPAP/BIPAP (for sleep apnea), change in frequency of use or settings within the previous 6 months
History of treatment with growth hormone
Neurodevelopmental disorder severe enough to impair ability to comply with study protocol
Clinical diagnosis of bipolar illness, schizophrenia, conduct disorder, and/or substance use/abuse
Females: currently pregnant, planning to become pregnant, or unwilling to use 2 or more acceptable methods of contraception when engaging in sexual activity throughout the study
Tobacco use
Liver/renal dysfunction
ALT or AST >2 times the upper limit of normal
Bicarbonate <18 mmol/L
Creatinine >1.2 mg/dL
History of pancreatitis
Personal- and/or family history of medullary thyroid carcinoma
Personal- and/or family history of multiple endocrine neoplasia type 2
Calcitonin level >50 ng/L
Bulimia nervosa
Neurological disorder
Hypothalamic obesity
Obesity associated with genetic disorder (monogenetic obesity)
Hyperthyroidism or uncontrolled hypothyroidism
History of suicide attempt
History of suicidal ideation or self-harm within the past year
History of cholelithiasis

Treatment and study plan

Weight loss with pharmacotherapy

Drug

Participants randomized to the drug intervention group will receive Exenatide extended-release.

Other names: Exenatide extended release

Weight loss without pharmacotherapy

Drug

Participants randomized to the placebo group will receive a placebo.

Other names: Placebo

Primary outcomes

Body Mass Index

Time frame: 52 weeks

Percentage of body mass index change from Randomization to Week 52

Sponsors and collaborators

Lead sponsor

University of Minnesota

Other

Registry information

Important dates

Study start: 2015
Primary completion: 2020
Study completion: 2020
First posted: Jul 14, 2015
Registry last updated: Jan 3, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed