Physiologic Response to Bariatric Surgery and the Impact of Adjunct Semaglutide in Adolescents (PRESSURE)

University of Colorado Denver (CU Denver)

Status and phase: Enrolling; Phase 1

Conditions: Anti-obesity Agents; Bariatric Surgery; Obesity; Adolescent Obesity; Body-Weight Trajectory; Weight Loss Trajectory

Treatments: Behavioral: Standard postoperative care; Drug: Injectable semaglutide

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06575738

21-3604

5K23HL163480-02 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The study plans to learn more about what happens to the body after bariatric surgery in people 12 to 24 years old. The study aims to understand why people respond differently to bariatric surgery and how to define success beyond weight loss alone. The study also plans to learn more about whether a medication (semaglutide) can help people 12 to 24 years old who, between 1 and 2 years after bariatric surgery, have not lost as much weight as expected.

Enrollment: 40 estimated patients

Sex: All

Ages: 12 to 24 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Observation Phase

Inclusion Criteria:

• Signed and dated informed consent form
• Willingness to comply with all study procedures and availability for the duration of the study
• Male or female biological sex, age 12 through 24 years
• In the preoperative pathway for vertical sleeve gastrectomy

Exclusion Criteria:

• Planned Roux-en-Y gastric bypass
• Hypothalamic obesity
• Type 2 Diabetes
• Current use of oral glucocorticoids (i.e. within 10 days of baseline visit)
• Current use of insulin

Intervention/Treatment Phase

Inclusion Criteria:

• Signed and dated informed consent form
• Status post vertical sleeve gastrectomy
• Male or female biological sex, age 12 through 24 years
• Meeting minimum nutrition goals
• Obesity: age 12-17 years: BMI ≥95th%ile for age/sex | age 18-24 years: BMI ≥ 30kg/m^2
• If entering the Intervention phase from the Observational phase: ≤20% BMI loss at 1 year postop
• If entering the Intervention phase from the existing patient pool: ≤20% BMI loss at 1-2 years postop

Exclusion Criteria:

• Surgically correctable cause of suboptimal postoperative weight loss
• Known hypersensitivity to any component of semaglutide
• Personal or family history of medullary thyroid carcinoma
• Personal history of multiple endocrine neoplasia type 2
• Hypothalamic Obesity
• Type 2 Diabetes
• History of pancreatitis
• Uncontrolled hypertension
• Clinically significant arrhythmia or heart disease that could be exacerbated by increased heart rate
• Malignant neoplasm within the last 5 years
• Untreated thyroid disorder
• Tanner Stage 1
• Baseline alanine transaminase (ALT) or aspartate aminotransferase (AST) ≥ 5x upper limit of normal
• Baseline Creatinine >1.2mg/dL
• Active treatment for bulimia nervosa
• Active major psychiatric disorder limiting informed consent
• Suicidal ideation of type 4 or 5 on Columbia-Suicide Severity Rating Scale (C-SSRS)
• Intentional self-harm within the previous 1 month
• Severe unmanaged depression, defined by Center for Epidemiological Studies Depression (CESD) score of 26 or greater and by clinical evaluation
• Recent change to concomitant medications for hypertension, dyslipidemia, depression or anxiety (<4 weeks prior to enrollment)
• Use of oral glucocorticoids (within 10 days of baseline visit)
• Use of metformin (within 3 months of baseline visit)
• Use of insulin secretagogues (within 4 half-lives of the medication of baseline visit)
• Current use of insulin
• Use of anti-obesity medications (within 4 half-lives of the medication of baseline visit)
• Current pregnancy
• For females of reproductive potential: Plan to become pregnant in the next 8 months
• For females of reproductive potential: Not on contraception (i.e. two forms of birth control for example oral birth control pills and condoms) for at least 1 month prior to enrollment and agreement to use these during study participation and for an additional 8 weeks after the final dose of study medication

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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40 participants in 3 patient groups

Observational

No Intervention group

Description:

Participants complete a set of standardized measures before bariatric surgery, 3 months postoperatively, and 12 months postoperatively.

Active Medication + Standard Postoperative Care

Experimental group

Description:

Participants can be enrolled between 1 and 2 years postoperatively and will receive usual interdisciplinary postoperative care plus weekly subcutaneous injectable semaglutide for 26 weeks. Initial dose is 0.25mg and is escalated every 4 weeks as tolerated (0.5mg, 1.0mg, 1.7mg, 2.4mg) for a total exposure of 26 weeks.

Treatment:

Drug: Injectable semaglutide

Behavioral: Standard postoperative care

Standard Postoperative Care

Active Comparator group

Description:

Participants can be enrolled between 1 and 2 years postoperatively and will receive usual interdisciplinary postoperative care.

Treatment:

Behavioral: Standard postoperative care