Enhancing Weight Loss Maintenance With GLP-1RA (BYDUREON™) in Adolescents With Severe Obesity
Condition: Severe Obesity
MeSH terms: Obesity; Obesity, Morbid; Weight Loss
Intervention: Weight loss with pharmacotherapy; Weight loss without pharmacotherapy
Intervention description: Participants randomized to the drug intervention group will receive Exenatide extended-release.; Participants randomized to the placebo group will receive a placebo.
Intervention MeSH terms: Exenatide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
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)
Enrollment: 100.0
Sex: All
Minimum age: 12 Years
Maximum age: 17 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Obesity; Pharmacotherapy; GLP-1; Children; Exenatide; BYDUREON; Weight Loss; Maintenance

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.
    

Eligibility criteria:

        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