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

December 1, 2021 updated by: University of Minnesota
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 17 years (CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Weight Loss Maintenance without Pharmacotherapy
Individuals who, after a short-term (1-3 month) meal replacement induction period, achieve ≥5% BMI reduction. A selection of these participants are then randomized to receive treatment with placebo.
Drug: Weight loss without pharmacotherapy
Participants randomized to the placebo group will receive a placebo.
Other Names:
  • Placebo
ACTIVE_COMPARATOR: Weight Loss Maintenance with Pharmacotherapy
Individuals who, after a short-term (1-3 month) meal replacement induction period, achieve a >/= 5% BMI reduction. A selection of these participants are then randomized to receive treatment with GLP-1RA.
Drug: Weight loss with pharmacotherapy
Participants randomized to the drug intervention group will receive Exenatide extended-release.
Other Names:
  • Exenatide extended release

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Body Mass Index
Time Frame: 52 weeks
Percentage of body mass index change from Randomization to Week 52
52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Minnesota

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2015

Primary Completion (ACTUAL)

August 14, 2020

Study Completion (ACTUAL)

August 14, 2020

Study Registration Dates

First Submitted

July 6, 2015

First Submitted That Met QC Criteria

July 9, 2015

First Posted (ESTIMATE)

July 14, 2015

Study Record Updates

Last Update Posted (ACTUAL)

January 3, 2022

Last Update Submitted That Met QC Criteria

December 1, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1505M72081

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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