Physiologic Response to Bariatric Surgery and the Impact of Adjunct Semaglutide - in Adolescents (the PRESSURE Trial)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Observational phase: Change in fasting glucagon-like peptide-1 (GLP1), measured by blood levels
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 24 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Observational
Participants complete a set of standardized measures before bariatric surgery, 3 months postoperatively, and 6 months postoperatively.
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.
干预措施: Standard postoperative care (Behavioral)
Standard Postoperative Care
Participants can be enrolled between 6 to 24 months postoperatively and will receive usual interdisciplinary postoperative care.
干预措施: Standard postoperative care (Behavioral)
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.
干预措施: Injectable semaglutide or injectable tirzepatide (Drug)
结局指标
主要结局
Observational phase: Change in fasting glucagon-like peptide-1 (GLP1), measured by blood levels
时间窗: Baseline, 12 months postoperatively
GLP1 levels are measured prior to an oral mixed meal tolerance test
Observational phase: Change in stimulated glucagon-like peptide-1 (GLP1), measured by blood levels
时间窗: Baseline, 12 months postoperatively
GLP1 levels are measured during an oral mixed meal tolerance test
Observational phase: Change in indexed left ventricular mass (g/m to the 2.7th power), measured by echocardiogram
时间窗: Baseline, 12 months postoperatively
Resting supine 2-dimensional echocardiogram
Observational phase: Change in insulin sensitivity (IS), measured by fasting blood insulin levels
时间窗: Baseline, 12 months postoperatively
Fasting insulin levels are measured. IS is defined as 1/fasting insulin
Observational phase: Change in percent fat free mass (FFM), measured by whole body dual-energy X-ray absorptiometry (DXA)
时间窗: Baseline, 12 months postoperatively
Percent FFM is calculated as (1-Percent Fat Mass) from DXA
Intervention phase: Change in BMI
时间窗: Baseline, 26 weeks
\[(BMI at 26 weeks-Weight at Intervention Baseline)\]/(BMI at Intervention Baseline)\] \* 100
Observational phase: Change in resting metabolic rate (RMR), measured by canopy indirect calorimetry
时间窗: Baseline, 12 months postoperatively
RMR from canopy indirect calorimetry
Observational phase: Change in 24 hour systolic blood pressure (BP), measured by ambulatory BP monitor
时间窗: Baseline, 12 months postoperatively
Mean 24 hour systolic BP
Observational phase: Change in fasting glucagon-like peptide-1 (GLP1), measured by blood levels
时间窗: Baseline, 6 months postoperatively
GLP1 levels are measured prior to an oral mixed meal tolerance test
Observational phase: Change in stimulated glucagon-like peptide-1 (GLP1), measured by blood levels
时间窗: Baseline, 6 months postoperatively
GLP1 levels are measured during an oral mixed meal tolerance test
Observational phase: Change in insulin sensitivity (IS), measured by fasting blood insulin levels
时间窗: Baseline, 6 months postoperatively
Fasting insulin levels are measured. IS is defined as 1/fasting insulin
Observational phase: Change in percent fat free mass (FFM), measured by whole body dual-energy X-ray absorptiometry (DXA)
时间窗: Baseline, 6 months postoperatively
Percent FFM is calculated as (1-Percent Fat Mass) from DXA
Observational phase: Change in resting metabolic rate (RMR), measured by canopy indirect calorimetry
时间窗: Baseline, 6 months postoperatively
RMR from canopy indirect calorimetry
Observational phase: Change in 24 hour systolic blood pressure (BP), measured by ambulatory BP monitor
时间窗: Baseline, 6 months postoperatively
Mean 24 hour systolic BP
Observational phase: Change in indexed left ventricular mass (g/m to the 2.7th power), measured by echocardiogram
时间窗: Baseline, 6 months postoperatively
Resting supine 2-dimensional echocardiogram
次要结局
- Change in fasting Peptide YY (PYY), measured by blood levels(Baseline, 12 months postoperatively)
- Change in stimulated Peptide YY (PYY), measured by blood levels(Baseline, 12 months postoperatively)
- Intervention Phase: Eligibility rate(Up to 150 weeks)
- Intervention Phase: Mean maximum tolerated semaglutide dose(Baseline, 26 weeks)
- Change in fasting glucagon-like peptide-1 (GLP1), measured by blood levels(Baseline, 3 months postoperatively)
- Change in stimulated glucagon-like peptide-1 (GLP1), measured by blood levels(Baseline, 3 months postoperatively)
- Change in fasting ghrelin, measured by blood levels(Baseline, 12 months postoperatively)
- Change in stimulated ghrelin, measured by blood levels(Baseline, 12 months postoperatively)
- Change in insulin sensitivity (IS), measured by fasting blood insulin levels(Baseline, 3 months postoperatively)
- Change in 24 hour systolic blood pressure (BP), measured by ambulatory BP monitor(Baseline, 3 months postoperatively)
- Change in percent fat free mass (FFM), measured by whole body dual-energy X-ray absorptiometry (DXA)(Baseline, 3 months postoperatively)
- Change in resting metabolic rate (RMR), measured by canopy indirect calorimetry(Baseline, 3 months postoperatively)
- Change in indexed left ventricular mass (g/m to the 2.7th power), measured by echocardiogram(Baseline, 3 months postoperatively)
- Intervention Phase: Enrollment rate(Up to 154 weeks)
- Intervention Phase: Retention rate(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(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(Up to 30 weeks)
- Change in fasting Peptide YY (PYY), measured by blood levels(Baseline, 6 months postoperatively)
- Change in stimulated Peptide YY (PYY), measured by blood levels(Baseline, 6 months postoperatively)
- Change in fasting ghrelin, measured by blood levels(Baseline, 6 months postoperatively)
- Change in stimulated ghrelin, measured by blood levels(Baseline, 6 months postoperatively)
- Intervention Phase: Mean maximum tolerated semaglutide dose or tirzepatide dose(Baseline, 26 weeks)
- Change in fasting Peptide YY (PYY), measured by blood levels(Baseline, 3 months postoperatively)
- Change in stimulated Peptide YY (PYY), measured by blood levels(Baseline, 3 months postoperatively)
- Change in fasting ghrelin, measured by blood levels(Baseline, 3 months postoperatively)
- Change in stimulated ghrelin, measured by blood levels(Baseline, 3 months postoperatively)