Enhancing Weight Loss Maintenance With GLP-1RA (BYDUREON™) in Adolescents With Severe Obesity
Condition: Severe Obesity
MeSH terms: Obesity; Obesity, Morbid; Weight Loss
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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).
    

Intervention name(s): Weight loss with pharmacotherapy; Weight loss without pharmacotherapy
Intervention type(s): Drug; Drug
Intervention description(s): Participants randomized to the drug intervention group will receive Exenatide extended-release.; Participants randomized to the placebo group will receive a placebo.
Other intervention name(s): Exenatide extended release; Placebo
Intervention MeSH terms: Exenatide
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Individuals who consented to the project were enrolled in a screening phase of the study where they received meal replacement therapy in attempt to achieve a >/= 5% body mass reduction. Individuals who did not meet this goal were considered screen failures. Individuals who met this goal were allowed to remain in the study and be randomized to one of the treatment arms (placebo or GLP-1 RA).
A total of 100 participants consented and were enrolled and 66 participants achieved the required BMI reduction with MRT and were randomized to study treatment (33 to GLP-1 RA (exenatide) and 33 to placebo).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Obesity; Pharmacotherapy; GLP-1; Children; Exenatide; BYDUREON; Weight Loss; Maintenance