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

• ClinicalTrials.gov Identifier: NCT04883346
• Recruitment Status: Recruiting
• First Posted: May 12, 2021
• Last Update Posted: June 24, 2022
• Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )

Study Description

Brief 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 7 study visits....

Condition or disease	Intervention/treatment	Phase
Obesity; Status Post Sleeve Gastrectomy	Drug: Liraglutide	Phase 2

Detailed Description:

This 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 greater than or equal to 30 or BMI greater than or equal to 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.

The Primary objective is 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. Up to 50 adolescents and young adults (age 12-20) will be recruited to treat up to 40 with liraglutide for 16 weeks.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Liraglutide (Saxenda(R), Novo Nordisk) in Adolescents With Obesity After Sleeve Gastrectomy: A Pilot Open-Label Study
• Actual Study Start Date: June 21, 2021
• Estimated Primary Completion Date: July 1, 2022
• Estimated Study Completion Date: October 1, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Liraglutide; Treated with Liraglutide	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.

Outcome Measures

Primary Outcome Measures :

1. Change in BMI [ Time Frame: 16 weeks ]
   The change in BMI (kg/m2) measured from the baseline visit to the week 16 visit will be used to inform a power calculation for a subsequent trial.

Secondary Outcome Measures :

1. Change in Fat Mass [ Time Frame: 16 weeks ]
   Change in fat mass (in kg) from baseline to the week 16 visit
2. Change in BMI [ Time Frame: 16 weeks ]
   The change in BMI (kg/m2) from baseline to the week 16 visit

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 20 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Male or female, 12-20.999 years at screening visit
2. 12 months or more status-post vertical sleeve gastrectomy with a maximum of 10 years after surgery
3. BMI 30 kg/m2 or greater than or equal to 95th percentile for age and sex
4. In good general health as evidenced by medical history
5. Ability to take subcutaneous medication and be willing to adhere to the daily subcutaneous liraglutide regimen
6. Ability to provide consent/assent before any trial-related activities as required per protocol
7. Stated availability for the duration of the study

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Current or recent (within 3 months of start of study drug initiation) use of weight loss medications such as phentermine, topiramate, lisdexamfetamine (prescribed specifically for weight loss; when prescribed for ADHD and dose is stable for last 3 months this medication will be allowed), orlistat, and naltrexone HCl/bupropion HCl, or liraglutide
2. Weight of more than 450 lbs. (because Dual-Energy X-ray Absorptiometry (DXA) scanning cannot be done in those exceeding this weight)
3. Current use of insulin or sulfonylurea or other medication affecting insulin secretion or GLP1 clearance such as a DPPIV inhibitor
4. Weight loss of more than 3% of body weight in the past 2 months
5. Current pregnancy, desire to become pregnant within study period, current lactation or, if sexually active, not willing to use adequate contraceptive measures
6. History of recurrent pancreatitis (greater than 2 episodes)
7. History of chronic kidney disease (eGFR <60)
8. History of gastroparesis
9. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
10. History of prior metabolic and bariatric surgery other than vertical sleeve gastrectomy
11. Current or prior use of any GLP-1 agonist medication during the 6 months before screening, including liraglutide.
12. Known or suspected allergy to trial medication, excipients, or related products
13. Treatment with another investigational drug or other experimental intervention within 3 months prior to enrollment in this trial
14. Individuals who have current substance abuse or a DSM 5 Axis I psychiatric disorder or DSM Axis II Mental Retardation diagnosis that in the opinion of the investigators would impede competence, compliance, or participation in the study
15. Suicidal ideation type 4 or 5, history of past suicide attempt, and suicidal behavior in the past month
16. Presence of a major medical illness not listed above

Contacts and Locations

Contacts

Contact: Anna Zenno, M.D.; (301) 451-0396; anna.zenno@nih.gov

Contact: Jack A Yanovski, M.D.; (301) 496-0858; jy15i@nih.gov

Locations

United States, Maryland

National Institutes of Health Clinical Center; Recruiting

Bethesda, Maryland, United States, 20892

Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 prpl@cc.nih.gov

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Jack A Yanovski, M.D.; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

Publications:

Kelly AS, Auerbach P, Barrientos-Perez M, Gies I, Hale PM, Marcus C, Mastrandrea LD, Prabhu N, Arslanian S; NN8022-4180 Trial Investigators. A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity. N Engl J Med. 2020 May 28;382(22):2117-2128. doi: 10.1056/NEJMoa1916038. Epub 2020 Mar 31.

Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, Lau DC, le Roux CW, Violante Ortiz R, Jensen CB, Wilding JP; SCALE Obesity and Prediabetes NN8022-1839 Study Group. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med. 2015 Jul 2;373(1):11-22. doi: 10.1056/NEJMoa1411892.

Inge TH, Courcoulas AP, Jenkins TM, Michalsky MP, Helmrath MA, Brandt ML, Harmon CM, Zeller MH, Chen MK, Xanthakos SA, Horlick M, Buncher CR; Teen-LABS Consortium. Weight Loss and Health Status 3 Years after Bariatric Surgery in Adolescents. N Engl J Med. 2016 Jan 14;374(2):113-23. doi: 10.1056/NEJMoa1506699. Epub 2015 Nov 6.

• Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• ClinicalTrials.gov Identifier: NCT04883346
• Other Study ID Numbers: 10000241; 000241-CH
• First Posted: May 12, 2021
• Last Update Posted: June 24, 2022
• Last Verified: March 28, 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: .Individual data for all IPD that underlie results in a publication will be made available.
• Supporting Materials: Study Protocol; Informed Consent Form (ICF)
• Time Frame: Data will be available starting 6 months after publication or after 1 year following study closure.
• Access Criteria: Data will be stored in NIH CTDB and will be made available to university-based researchers on reasonable request to the Principal Investigator following establishment of a data sharing agreement.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ):

Children; glucagon-like peptide; Weight Loss; pharmacotherapy for obesity; Bariatric Surgery

Additional relevant MeSH terms:

Obesity; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Liraglutide; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists