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

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ClinicalTrials.gov Identifier: NCT02496611
Recruitment Status : Recruiting
First Posted : July 14, 2015
Last Update Posted : March 25, 2019
Sponsor:
Information provided by (Responsible Party):
University of Minnesota

Brief 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.

Condition or disease Intervention/treatment Phase
Severe Obesity Drug: Exenatide extended-release for injectable suspension (BYDUREON™) Dietary Supplement: Meal Replacement Therapy Phase 2

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). Moreover, GLP-1RA treatment will result in superior maintenance of initial reductions of body fat (total, visceral, and subcutaneous), blood pressure, triglycerides/HDL ratio, inflammation, oxidative stress, postprandial glucose-insulin response, insulin resistance, β cell dysfunction, and arterial stiffness at 52 weeks.

Secondary Objectives Investigate the mechanisms by which GLP-1RA treatment facilitates weight loss maintenance and identify predictors of response to treatment. The investigators hypothesize that compared to placebo, GLP-1RA treatment following a period of meal replacement will reduce appetite (and related hormones) and gastric emptying rate, and will increase satiety (and related hormones) and resting energy expenditure at 26- and 52 weeks following randomization. Moreover, based on our preliminary work, the investigator hypothesize that appetite (and appetite-related hormones) following the meal replacement period and female gender will be associated with superior weight loss maintenance with GLP-1RA treatment.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Enhancing Weight Loss Maintenance With GLP-1RA (BYDUREON™) in Adolescents With Severe Obesity
Study Start Date : December 2015
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : January 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Exenatide

Arm Intervention/treatment
Experimental: Meal Replacement Therapy
A short-term (1-3 month) meal replacement induction period design to achieve ≥5% BMI reduction. If participants achieve ≥5% BMI they will be randomized to drug or placebo in phase 2 of the trail.
Dietary Supplement: Meal Replacement Therapy
A short-term meal replacement induction period designed to achieve >5% BMI reduction in 1, 2, or 3 months.

Placebo Comparator: Weight Loss Maintenance with Pharmacotherapy
We 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)
Drug: Exenatide extended-release for injectable suspension (BYDUREON™)



Primary Outcome Measures :
  1. Weight loss maintenance [ Time Frame: 52 weeks ]
    Maintenance of ≥5% BMI reduction will be achieved with GLP-1RA (BYDUREON™) from baseline to the 52-week time point.


Secondary Outcome Measures :
  1. Maintenance of body fat changes [ Time Frame: 52 weeks ]
    Maintenance of initial reductions of body fat (total (kg), visceral (kg), and subcutaneous (kg)) will be achieved at 52 weeks with GLP-1RA.

  2. Maintenance of blood pressure [ Time Frame: 52 weeks ]
    Maintenance of initial reductions systolic blood pressure (mmHg) will be achieved at 52 weeks with GLP-1RA (BYDUREON™).

  3. Maintenance of improved insulin sensitivity [ Time Frame: 52 weeks ]
    Maintenance of insulin sensitivity will be achieved at 52 weeks with GLP-1RA (BYDUREON™).

  4. Reduced liver fat content [ Time Frame: 26 weeks ]
    Reduce liver fat content (hepatic fat fraction) measured by MRI



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02496611


Locations
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United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Ann E Sheldon, B.S.    612-626-3813    shel0230@umn.edu   
Principal Investigator: Aaron S Kelly, Ph.D.         
Sponsors and Collaborators
University of Minnesota

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Minnesota
ClinicalTrials.gov Identifier: NCT02496611     History of Changes
Other Study ID Numbers: 1505M72081
First Posted: July 14, 2015    Key Record Dates
Last Update Posted: March 25, 2019
Last Verified: March 2019
Keywords provided by University of Minnesota:
Obesity
Pharmacotherapy
GLP-1
Children
Exenatide
BYDUREON
Weight Loss
Maintenance
Additional relevant MeSH terms:
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Obesity
Obesity, Morbid
Weight Loss
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Body Weight Changes
Exenatide
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Obesity Agents
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists