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

NCT02496611 | Completed Phase 2 Results DMC

• 1 other identifier: 1505M72081
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Severe Obesity

Keywords

Obesity; Pharmacotherapy; GLP-1; Children; Exenatide; BYDUREON; Weight Loss; Maintenance

Outcome Measures

Primary Outcomes (1)

• Body Mass Index

  Percentage of body mass index change from Randomization to Week 52

  52 weeks

Study Arms (2)

Weight Loss Maintenance without Pharmacotherapy

PLACEBO COMPARATOR

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

Weight Loss Maintenance with Pharmacotherapy

ACTIVE COMPARATOR

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

Interventions

Weight loss with pharmacotherapy DRUG

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

Also known as: Exenatide extended release

Weight Loss Maintenance with Pharmacotherapy

Weight loss without pharmacotherapy DRUG

Participants randomized to the placebo group will receive a placebo.

Also known as: Placebo

Weight Loss Maintenance without Pharmacotherapy

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (2)

• Fox CK, Clark JM, Rudser KD, Ryder JR, Gross AC, Nathan BM, Sunni M, Dengel DR, Billington CJ, Bensignor MO, Kelly AS. Exenatide for weight-loss maintenance in adolescents with severe obesity: A randomized, placebo-controlled trial. Obesity (Silver Spring). 2022 May;30(5):1105-1115. doi: 10.1002/oby.23395. Epub 2022 Apr 10.

  PMID: 35403350 DERIVED

• Ryder JR, Kaizer AM, Rudser KD, Daniels SR, Kelly AS. Utility of Body Mass Index in Identifying Excess Adiposity in Youth Across the Obesity Spectrum. J Pediatr. 2016 Oct;177:255-261.e2. doi: 10.1016/j.jpeds.2016.06.059. Epub 2016 Aug 2.

  PMID: 27496270 DERIVED

MeSH Terms

Conditions

Obesity, Morbid; Obesity; Weight Loss

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Intervention Hierarchy (Ancestors)

Therapeutics

Results Point of Contact

• Title: Aaron Kelly PhD
• Organization: University of Minnesota

kelly105@umn.edu

6126253492

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: July 6, 2015
• First Posted: July 14, 2015
• Study Start: December 1, 2015
• Primary Completion: August 14, 2020
• Study Completion: August 14, 2020
• Last Updated: January 3, 2022
• Results First Posted: January 3, 2022

Record last verified: 2021-12

Locations

US (1)