JOULE - Metabolic Adaptation to Weight Loss in Response to a Behavioural Lifestyle Program With or Without Semaglutide in Adolescents With Obesity - a Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 74
- 试验地点
- 1
- 主要终点
- Measurement of Adaptive thermogenesis
研究概览
简要总结
The Joule MARS study is a single center, randomized, open label clinical trial aiming to explore the metabolic adaptations that occur in response to weight management in adolescents with obesity. Behavioural lifestyle intervention with and without a pharmacological intervention - semaglutide- will be studied. Study participants will be randomized to one of two groups. Group A will follow a behavioral lifestyle program (BLP) alone for 6 months, followed by BLP and treatment with semaglutide for six months. Group B will be enrolled in BLP and semaglutide from baseline to 6 months. The primary research question will assess, in youth aged 12-17 years diagnosed with obesity and enrolled in a weight management program, if the implementation of a BLP together with semaglutide, compared to the implementation of BLP alone for 6 months leads to less adaptive thermogenesis.
详细描述
The Joule MARS (Metabolic Adaptation to weight loss in Response to a behavioural lifestyle program with or without Semaglutide in adolescents with obesity) study is a single-center, randomized controlled trial designed to investigate the effects of a behaviour lifestyle program and the medication semaglutide on resting energy expenditure (REE), work efficiency during standard exercise on a cycle ergometer and related metabolic outcomes in adolescents with obesity. The study will involve two intervention groups:
Group A will participate in a behavioral lifestyle program (BLP) alone for 6 months followed by a combination of semaglutide treatment and a BLP for an additional 6 months.
Group B will receive semaglutide and a BLP for the first 6 months and then terminate the study.
The study objectives are to determine if, in youth aged 12-17 years with obesity and enrolled in a weight management program:
- the implementation of a BLP and semaglutide, compared to the implementation of a BLP alone leads to less adaptive thermogenesis (AT) at 6 months;
- the implementation of a BLP and semaglutide, compared to the implementation of a BLP alone for 6-month, leads to:
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
- None
入排标准
- 年龄范围
- 12 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Youth aged 12-17 years
- •Diagnosed with obesity (BMI ≥2 standard deviations above WHO Reference median)
- •Enrolled in Growing Health Weight Management or Next Step pediatric clinics (ie. have at least one year of the program remaining).
排除标准
- •Any contraindications for MRI (i.e. claustrophobia, implanted metal, metallic injuries recent tattoo or weight >300lb. Ineligible for imaging visit only.
- •Use of atypical anti-psychotics.
- •Use of the following medication classes: (i.e. Beta-blocker medications, Steatogenic medications, Anti-hyperglycemic medications, HIV drugs, Antidepressants, anxiolytic drugs, anti-psychotic drugs, Thyroid drugs, Antiemetic or amphetamine, dextromethorphan and metoclopramide.)
- •Elevated alanine aminotransferase (ALT) > 5 x upper range of normal at screening.
- •Use of glucose lowering or any anti-obesity medication in the previous 3 months.
- •Known monogenic, syndromic or hypothalamic causes of obesity.
- •Diagnosis of type 1 or 2 diabetes mellitus.
- •Prior bariatric surgery or liver transplantation.
- •Alcohol intake exceeding 3 drinks per week or reported cannabis use.
- •Recent history of cigarette smoking (previous 3 months) - ineligible for imaging only.
- •History or family history of multiple endocrine neoplasia 2 or medullary thyroid cancer.
- •History of pancreatitis.
- •Presence of untreated endocrine disorder.
- •History of an eating disorder and / or history of suicidal ideation
- •History of a cardiac condition that precludes exercise testing or unable to have exercise testing done in the GHWM pediatric clinic, inability to use a cycle ergometer.
- •Participant who does not have a peak power value obtained in the GHWM pediatric clinic
- •Female who is pregnant, breast-feeding or intends to become pregnant.
- •Female who refuses to use a means of contraception if sexually active.
- •Participation in any interventional clinical study within 90 days before screening.
研究组 & 干预措施
BLP, then BLP+semaglutide
Group A will engage in a BLP alone for the first six months of the study, then receive BLP and semaglutide (Wegovy®) for the last six months of the study, beginning with 0.25 mg subcutaneously weekly and being titrated every four weeks up to a maximum of 2.4 mg in approved doses 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg.
干预措施: Semaglutide Pen Injector (Drug)
BLP, then BLP+semaglutide
Group A will engage in a BLP alone for the first six months of the study, then receive BLP and semaglutide (Wegovy®) for the last six months of the study, beginning with 0.25 mg subcutaneously weekly and being titrated every four weeks up to a maximum of 2.4 mg in approved doses 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg.
干预措施: Behavioural Lifestyle Program (BLP) (Behavioral)
BLP and semaglutide
In addition to BLP, Group B will receive semaglutide (Wegovy®) titrated to maximal dose tolerated, in approved doses of 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg subcutaneously weekly for 6 months .
干预措施: Semaglutide Pen Injector (Drug)
BLP and semaglutide
In addition to BLP, Group B will receive semaglutide (Wegovy®) titrated to maximal dose tolerated, in approved doses of 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg subcutaneously weekly for 6 months .
干预措施: Behavioural Lifestyle Program (BLP) (Behavioral)
结局指标
主要结局
Measurement of Adaptive thermogenesis
时间窗: 6, 12 months
Adaptive thermogenesis will be calculated as the difference between measured and predicted REE after the intervention. Measured REE will be assessed with the participant awake, but at rest, in a whole room indirect calorimeter. Predicted REE will be calculated based on an equation derived using baseline data from this study population as is currently recommended. Variables that will be considered in deriving the equation include fat-free mass, fat mass, age and sex. We will compare adaptive thermogenesis (primary outcome) and work efficiency between the two treatments utilizing linear regression analysis. Separate analyses for males and females will ensure relevance of study findings to both sexes.
次要结局
- Changes in energy work efficiency from baseline during standardized exercise(Baseline, 6, 12 months)
- Brown Adipose Tissue (BAT) activity(From enrollment to 6 months and to 12 months)
- Health-related quality of life (HRQoL)(Baseline to 6 months and to 12 months)
- Depressive symptoms(Baseline to 6 months and 12 months)
- Total body mass, fat mass and lean mass(Baseline, 6, 12 months)
- Anxiety symptoms(Baseline to 6 months and to 12 months)
- Hepatic fat content(Baseline, 6, 12 months)
- Hepatic stiffness(Baseline, 6 and 12 months)
- Fasting lipid profile(Baseline, 6, 12 months)
- Fasting insulin(Baseline, 6, 12 months)
- Hemoglobin A1C(Baseline, 6 and 12 months)
- Alanine aminotransferase(Baseline, 3, 6, 9 and 12 months)