NCT04883346

Liraglutide (Saxenda(R)) in Adolescents With Obesity After Sleeve Gastrectomy

Phase II Trial of Liraglutide (Saxenda(R), Novo Nordisk) in Adolescents With Obesity After Sleeve Gastrectomy: A Pilot Open-Label Study

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) · NIH
• Sex: All
• Age: 12 Years – 20 Years
• Healthy volunteers: Not accepted

Summary

Background: Metabolic Bariatric Surgery, including a surgery called vertical sleeve gastrectomy, is the most effective weight loss treatment for severe obesity. However, many adolescents who have this surgery still have obesity 1 year later or regain weight. Researchers want to see if a drug can help. Objective: To learn if liraglutide can help adolescents who still have obesity 1 year or more after vertical sleeve gastrectomy lose additional weight. Eligibility: Healthy adolescents ages 12-20.99 years who are 1-10 years post vertical sleeve gastrectomy and have a BMI of 30 kg/m2 or \>=95th percentile for age and sex. Design: Participants will be screened with: Medical history Physical exam Questionnaires about their mood and feelings about their weight Blood and urine tests Nutrition counseling. They will keep a diet log. A test where they view and respond to pictures of food Wrist accelerometer set-up. They will wear an accelerometer (a device like a watch) on their wrist for 14 days. It will measure their physical activity. Some screening tests will be repeated during the study. Participants will have an oral glucose tolerance test. They will ingest a sweet liquid. Blood samples will be taken. Participants will take liraglutide daily for 16 weeks. They will learn how to inject it under their skin. Participants will have a body scan to measure muscle and fat. Participants will be invited to eat as much as they want at a buffet meal at NIH. How much food they eat will be calculated. They will assess their appetite and mood before and after the meal. Participation will last for 7 months. Participants will have up to 7 study visits....

Detailed description

Study Description: This trial is an open-label Phase II non-randomized pilot study conducted at the NIH Clinical Center to investigate the efficacy of daily subcutaneous injection of liraglutide, a glucagon-like peptide-1 (GLP1) analogue to promote reduction of body mass index (BMI) in adolescents who continue to have obesity (BMI (Bullet)30 or BMI \>=95th percentile for age and sex) 1 year or more after vertical sleeve gastrectomy (SG). We hypothesize that administration of liraglutide will be associated with reduction in BMI in such adolescents. Objectives: Primary objective: To determine the effect size for the change in BMI of liraglutide 3.0 mg daily subcutaneously at 16 weeks in adolescents who have obesity after SG, in order to use the observed changes to determine the sample size of a subsequent randomized, controlled investigation. Hypothesis: The Primary Endpoint is estimation of required sample size for a later randomized controlled trial through calculation of effect size for change in body mass index (BMI) from baseline to 16 weeks of liraglutide. The hypothesis is: The data will be sufficient to calculate the effect size for change in BMI from baseline to 16 weeks for a 2-group experiment (placebo versus liraglutide). Secondary objectives: To study the effects of 16 weeks of liraglutide 3.0 mg subcutaneously on change in mean BMI and fat mass in adolescents who underwent vertical sleeve gastrectomy (SG) \>=1y prior to study initiation but still have obesity or have a recrudescence of obesity despite surgery. To compare the effects of liraglutide on BMI and fat mass in enrolled participants who had a poor initial response to SG (\<20% BMI reduction at BMI nadir) vs. those with a typical post-SG weight loss (\>=20% BMI reduction at BMI nadir). Additional Objectives: To examine the effects of daily subcutaneous liraglutide in enrolled participants on changes in body composition, metabolic syndrome markers, energy intake, glucose tolerance, gastrointestinal (GI) hormone concentrations, appetite, free living physical activity, mood, suicidality, weight related quality of life, self-perception of body image, and secretome. Endpoints: Primary Endpoint: Estimation of required sample size for a later RCT through calculation of effect size for change in body mass index (BMI) from baseline to 16 weeks of liraglutide. Key Secondary Endpoints: Changes in BMI and fat mass after 16 weeks of liraglutide Comparison of changes in BMI and fat mass after 16 weeks of liraglutide in participants who had a poor initial response to SG (\<20% BMI reduction at BMI nadir) vs. those with a typical post-S weight loss (\>=20% BMI reduction at BMI nadir) Tolerability and safety of liraglutide 3.0 mg. Additional (exploratory) Endpoints: Change from baseline to 16 weeks of liraglutide in: 1. Proportion reducing BMI by at least 5% and 10% 2. BMI standard deviation score for age and sex (BMIz) 3. Body weight 4. Percentage total body fat mass by DXA 5. Appetite score using visual analog scale (VAS) 6. Attention bias to highly palatable images 7. Energy intake at buffet meal 8. Free living physical activity by accelerometry 9. Metabolic syndrome markers (waist circumference, systolic and diastolic blood pressure, lipids, fasting plasma glucose level) 10. Fasting plasma insulin and HOMA-IR index 11. 2-hour oral glucose tolerance test (OGTT) insulin and glucose measurements 12. Hemoglobin A1C 13. Plasma GI hormones (GLP-1 and PYY) during OGTT 14. Weight related quality of life (QoL) score 15. Beck Depression Inventory total score 16. Body-Esteem Scale Score for Adolescents and Adults 17. Columbia Suicide Severity Rating Scale 18. Secretome analysis 19. Stool microbiome analysis

Conditions

• Obesity
• Status Post Sleeve Gastrectomy

Interventions

Type	Name	Description
DRUG	Liraglutide	Liraglutide by subcutaneous injection administered daily. Dose will be initiated at 0.6mg per day and increased to a maximum of 3.0 mg per day as tolerated.

Timeline

• Start date: 2021-06-21
• Primary completion: 2024-03-15
• Completion: 2024-04-30
• First posted: 2021-05-12
• Last updated: 2024-11-20
• Results posted: 2024-11-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study