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

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

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 or tirzepatide) can help people 12 to 24 years old who, between 6 and 24 months after bariatric surgery, have not lost as much weight as expected.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Body-Weight Trajectory; Adolescent Obesity; Bariatric Surgery; Weight Loss Trajectory; Anti-obesity Agents
• Intervention / Treatment: Behavioral: Standard postoperative care; Drug: Injectable semaglutide or injectable tirzepatide

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jaime Moore, MD MPH; Phone Number: 303-724-8419; Email: jaime.moore@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Childrens Hospital Colorado
      • Contact: Jaime Moore, MD MPH; Phone Number: 303-724-8419; Email: jaime.moore@cuanschutz.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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: ≤22% BMI loss at 6-24 months postop
• If entering the Intervention phase from the existing patient pool: ≤22% BMI loss at 6-24 months 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Observational; Participants complete a set of standardized measures before bariatric surgery, 3 months postoperatively, and 6 months postoperatively.
Experimental: Active Medication + Standard Postoperative Care; Participants can be enrolled between 6 and 24 months postoperatively and will receive usual interdisciplinary postoperative care plus weekly subcutaneous injectable semaglutide or tirzepatide for 26 weeks. Initial dose is 0.25mg (semaglutide) or 2.5mg (tirzepatide) and is escalated every 4 weeks as tolerated up to the max dose of 2.4mg for semaglutide or 15mg for tirzepatide for a total exposure of 26 weeks.	Behavioral: Standard postoperative care; Standard postoperative care consists of behaviorally-focused interventions delivered by the interdisciplinary Bariatric Surgery Center team targeting nutrition, physical activity, sleep, and mental health at standard postoperative intervals.; Drug: Injectable semaglutide or injectable tirzepatide; Subcutaneous weekly injectable medication
Active Comparator: Standard Postoperative Care; Participants can be enrolled between 6 to 24 months postoperatively and will receive usual interdisciplinary postoperative care.	Behavioral: Standard postoperative care; Standard postoperative care consists of behaviorally-focused interventions delivered by the interdisciplinary Bariatric Surgery Center team targeting nutrition, physical activity, sleep, and mental health at standard postoperative intervals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intervention phase: Change in BMI	[(BMI at 26 weeks-Weight at Intervention Baseline)]/(BMI at Intervention Baseline)] * 100	Baseline, 26 weeks
Observational phase: Change in fasting glucagon-like peptide-1 (GLP1), measured by blood levels	GLP1 levels are measured prior to an oral mixed meal tolerance test	Baseline, 6 months postoperatively
Observational phase: Change in stimulated glucagon-like peptide-1 (GLP1), measured by blood levels	GLP1 levels are measured during an oral mixed meal tolerance test	Baseline, 6 months postoperatively
Observational phase: Change in insulin sensitivity (IS), measured by fasting blood insulin levels	Fasting insulin levels are measured. IS is defined as 1/fasting insulin	Baseline, 6 months postoperatively
Observational phase: Change in percent fat free mass (FFM), measured by whole body dual-energy X-ray absorptiometry (DXA)	Percent FFM is calculated as (1-Percent Fat Mass) from DXA	Baseline, 6 months postoperatively
Observational phase: Change in resting metabolic rate (RMR), measured by canopy indirect calorimetry	RMR from canopy indirect calorimetry	Baseline, 6 months postoperatively
Observational phase: Change in 24 hour systolic blood pressure (BP), measured by ambulatory BP monitor	Mean 24 hour systolic BP	Baseline, 6 months postoperatively
Observational phase: Change in indexed left ventricular mass (g/m to the 2.7th power), measured by echocardiogram	Resting supine 2-dimensional echocardiogram	Baseline, 6 months postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fasting glucagon-like peptide-1 (GLP1), measured by blood levels	GLP1 levels are measured prior to an oral mixed meal tolerance test	Baseline, 3 months postoperatively
Change in stimulated glucagon-like peptide-1 (GLP1), measured by blood levels	GLP1 levels are measured during an oral mixed meal tolerance test	Baseline, 3 months postoperatively
Change in fasting Peptide YY (PYY), measured by blood levels	PYY levels are measured prior to an oral mixed meal tolerance test	Baseline, 3 months postoperatively
Change in stimulated Peptide YY (PYY), measured by blood levels	Plasma PYY levels are measured during an oral mixed meal tolerance test	Baseline, 3 months postoperatively
Change in fasting ghrelin, measured by blood levels	Ghrelin levels are measured prior to an oral mixed meal tolerance test	Baseline, 3 months postoperatively
Change in stimulated ghrelin, measured by blood levels	Ghrelin levels are measured during an oral mixed meal tolerance test	Baseline, 3 months postoperatively
Change in insulin sensitivity (IS), measured by fasting blood insulin levels	Fasting insulin levels are measured. IS is defined as 1/fasting insulin	Baseline, 3 months postoperatively
Change in percent fat free mass (FFM), measured by whole body dual-energy X-ray absorptiometry (DXA)	Percent FFM is calculated as (1-Percent Fat Mass) from DXA	Baseline, 3 months postoperatively
Change in resting metabolic rate (RMR), measured by canopy indirect calorimetry	RMR from canopy indirect calorimetry	Baseline, 3 months postoperatively
Change in 24 hour systolic blood pressure (BP), measured by ambulatory BP monitor	Mean 24 hour systolic BP	Baseline, 3 months postoperatively
Change in indexed left ventricular mass (g/m to the 2.7th power), measured by echocardiogram	Resting supine 2-dimensional echocardiogram	Baseline, 3 months postoperatively
Intervention Phase: Eligibility rate	(Patients meeting inclusion and exclusion criteria/Total patients screened)*100	Up to 150 weeks
Intervention Phase: Enrollment rate	(Participants enrolled/Patients eligible)*100	Up to 154 weeks
Intervention Phase: Retention rate	(Participants completing all intervention visits/Patients enrolled)*100	Up to 184 weeks
Intervention Phase: Number of participants with at least one serious adverse event (AE) in the active medication group, measured by a count	Individual participants with serious AEs will be counted	Up to 30 weeks
Intervention Phase: Number of participants with an adverse event (AE) that leads to discontinuation of the medication, measured by a count	Participants experiencing an AE that leads to medication discontinuation will be counted	Up to 30 weeks
Change in fasting Peptide YY (PYY), measured by blood levels	PYY levels are measured prior to an oral mixed meal tolerance test	Baseline, 6 months postoperatively
Change in stimulated Peptide YY (PYY), measured by blood levels	Plasma PYY levels are measured during an oral mixed meal tolerance test	Baseline, 6 months postoperatively
Change in fasting ghrelin, measured by blood levels	Ghrelin levels are measured prior to an oral mixed meal tolerance test	Baseline, 6 months postoperatively
Change in stimulated ghrelin, measured by blood levels	Ghrelin levels are measured during an oral mixed meal tolerance test	Baseline, 6 months postoperatively
Intervention Phase: Mean maximum tolerated semaglutide dose or tirzepatide dose	Mean maximum tolerated dose (mg) of weekly injectable semaglutide or tirzepatide	Baseline, 26 weeks

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Jaime Moore, MD MPH, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: August 16, 2024
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 28, 2024

Study Record Updates

• Last Update Posted (Actual): July 15, 2026
• Last Update Submitted That Met QC Criteria: July 13, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Obesity; Semaglutide; Bariatric Surgery; Sleeve gastrectomy; Anti-obesity medication; Bariatric Surgery Post Operative Outcomes
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Body Weight Changes; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Body-Weight Trajectory; Obesity; Pediatric Obesity; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Semaglutide
• Other Study ID Numbers: 21-3604; 5K23HL163480-02 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No