Clinical trial NCT06575738: Physiologic Response to Bariatric Surgery and the Impact of Adjunct Semaglutide in Adolescents
Official title: Physiologic Response to Bariatric Surgery and the Impact of Adjunct Semaglutide - in Adolescents (the PRESSURE Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Obesity
Adolescent Obesity
Body-Weight Trajectory
Weight Loss Trajectory
Bariatric Surgery
Anti-obesity Agents
Keywords: Obesity
Anti-obesity medication
Bariatric Surgery
Bariatric Surgery Post Operative Outcomes
Semaglutide
Sleeve gastrectomy
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2024-08-28
Enrollment: 48
Sex: ALL
Minimum age (years): 12
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Observational phase: Change in fasting glucagon-like peptide-1 (GLP1), measured by blood levels
timeFrame: Baseline, 12 months postoperatively
measure: Observational phase: Change in stimulated glucagon-like peptide-1 (GLP1), measured by blood levels
timeFrame: Baseline, 12 months postoperatively
measure: Observational phase: Change in insulin sensitivity (IS), measured by fasting blood insulin levels
timeFrame: Baseline, 12 months postoperatively
measure: Observational phase: Change in percent fat free mass (FFM), measured by whole body dual-energy X-ray absorptiometry (DXA)
timeFrame: Baseline, 12 months postoperatively
measure: Observational phase: Change in resting metabolic rate (RMR), measured by canopy indirect calorimetry
timeFrame: Baseline, 12 months postoperatively
measure: Observational phase: Change in 24 hour systolic blood pressure (BP), measured by ambulatory BP monitor
timeFrame: Baseline, 12 months postoperatively
measure: Observational phase: Change in indexed left ventricular mass (g/m to the 2.7th power), measured by echocardiogram
timeFrame: Baseline, 12 months postoperatively
measure: Intervention phase: Change in BMI
timeFrame: Baseline, 26 weeks
Secondary outcomes:
measure: Change in fasting glucagon-like peptide-1 (GLP1), measured by blood levels
timeFrame: Baseline, 3 months postoperatively
measure: Change in stimulated glucagon-like peptide-1 (GLP1), measured by blood levels
timeFrame: Baseline, 3 months postoperatively
measure: Change in fasting Peptide YY (PYY), measured by blood levels
timeFrame: Baseline, 3 months postoperatively
measure: Change in fasting Peptide YY (PYY), measured by blood levels
timeFrame: Baseline, 12 months postoperatively
measure: Change in stimulated Peptide YY (PYY), measured by blood levels
timeFrame: Baseline, 3 months postoperatively
measure: Change in stimulated Peptide YY (PYY), measured by blood levels
timeFrame: Baseline, 12 months postoperatively
measure: Change in fasting ghrelin, measured by blood levels
timeFrame: Baseline, 3 months postoperatively
measure: Change in fasting ghrelin, measured by blood levels
timeFrame: Baseline, 12 months postoperatively
measure: Change in stimulated ghrelin, measured by blood levels
timeFrame: Baseline, 3 months postoperatively
measure: Change in stimulated ghrelin, measured by blood levels
timeFrame: Baseline, 12 months postoperatively
measure: Change in insulin sensitivity (IS), measured by fasting blood insulin levels
timeFrame: Baseline, 3 months postoperatively
measure: Change in percent fat free mass (FFM), measured by whole body dual-energy X-ray absorptiometry (DXA)
timeFrame: Baseline, 3 months postoperatively
measure: Change in resting metabolic rate (RMR), measured by canopy indirect calorimetry
timeFrame: Baseline, 3 months postoperatively
measure: Change in 24 hour systolic blood pressure (BP), measured by ambulatory BP monitor
timeFrame: Baseline, 3 months postoperatively
measure: Change in indexed left ventricular mass (g/m to the 2.7th power), measured by echocardiogram
timeFrame: Baseline, 3 months postoperatively
measure: Intervention Phase: Eligibility rate
timeFrame: Up to 150 weeks
measure: Intervention Phase: Enrollment rate
timeFrame: Up to 154 weeks
measure: Intervention Phase: Retention rate
timeFrame: Up to 184 weeks
measure: Intervention Phase: Mean maximum tolerated semaglutide dose
timeFrame: Baseline, 26 weeks
measure: Intervention Phase: Number of participants with at least one serious adverse event (AE) in the active medication group, measured by a count
timeFrame: Up to 30 weeks
measure: Intervention Phase: Number of participants with an adverse event (AE) that leads to discontinuation of the medication, measured by a count
timeFrame: Up to 30 weeks
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Childrens Hospital Colorado
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Jaime Moore, MD MPH
role: PRINCIPAL_INVESTIGATOR
References: