Effect of GLP-1 Receptor Agonist Therapy With and Without Exercise Training on Muscle Mass and Physical Function in People With Obesity
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Body composition
研究概览
简要总结
The use of glucagon-like peptide receptor agonists (GLP-1 RAs) may have clinically important effects on skeletal muscle mass (SMM), and physical function. The effects of exercise training in conjunction with GLP-1 RA therapy on these outcomes has not been studied. Additionally, most people treated with GLP-1-based weight loss medications stop taking these medications within 1 year of initiating treatment. This is an important clinical concern because weight regain can occur after weight loss pharmacotherapy is stopped and the impact of stopping GLP-1 RA therapy on physical and metabolic function has not been studied.
In this study, the investigators will conduct a 2-year randomized clinical trial to evaluate body composition, muscle, physical and metabolic function, muscle strength and appetite control and reward signaling in the brain in response to 1-year of GLP-1 RA therapy, with or without exercise training, and subsequent treatment cessation on muscle and appetite-related outcomes assessed 1-year after stopping treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •i) obesity (Body Mass Index ≥ 30 kg/m2)
- •ii) decreased physical function (Modified Physical Performance Test score 17 to 31)
- •iii) approval of their primary physician to participate in this study.
排除标准
- •i) unstable weight (>4% change during the last 2 months before entering the study)
- •ii) ≥150 min per week of structured exercise (e.g., jogging, activities that cause heavy breathing and sweating)
- •iii) diabetes
- •iv) significant cardiopulmonary disease (heart failure, angina, uncontrolled hypertension, chronic obstructive pulmonary disease) or other organ dysfunction (e.g., renal insufficiency [eGFR <30 mL/min/1.73 m2])
- •v) therapy with a GLP-1 or other weight loss medications
- •vi) clinically significant gastric emptying abnormality or chronically take drugs that directly affect gastrointestinal motility
- •vii) history of chronic or acute pancreatitis
- •viii) thyroid-stimulating hormone (TSH) >1.5X the upper limit of normal (patients receiving treatment for hypothyroidism may be included provided their thyroid hormone replacement dose has been stable for at least 3 months)
- •ix) history of significantly active or unstable Major Depressive Disorder or other severe psychiatric disorder (e.g. schizophrenia, bipolar disorder, or other serious mood or anxiety disorder) within the last 2 months that would interfere with study participation
- •x) acute or chronic hepatitis, or other liver disease other than Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD)
- •xi) family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
- •xii) history of active or untreated malignancy or are in remission from a clinically significant malignancy (other than basal- or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years
- •xiii) tobacco use, excessive alcohol intake (≥3 drinks/day for men and ≥2 drinks/day for women) or active substance abuse with illegal drugs by self-report, or regular marijuana use within 3 months of enrollment and unwilling to abstain from marijuana during the trial
- •xiv) Use of medications that are known to affect the study outcome measures or increase the risk of study procedures and that cannot be temporarily discontinued for this study
- •xv) have had bariatric surgery or plan to have endoscopic or bariatric surgery therapy for obesity
- •xvi) anemia (Hgb <10 g/dL)
- •xvii) Conditions that render subject unable to complete all testing procedures (e.g., severe ambulatory impairments, limb amputations, or metal implants that interfere with imaging procedures; coagulation disorders)
- •xii) history of seizure disorder
- •xix) Female who is pregnant, breast-feeding or intends to become pregnant
- •xx) allergy or hypersensitivity to GLP-1 RA medications
- •xxi) unable to grant voluntary informed consent
- •xxii) unable or unwilling to follow the study protocol or who, for any reason, the research team considers the participant is not an appropriate candidate for the study
研究组 & 干预措施
GLP-1 RA + Exercise
Participants in this group will receive semaglutide therapy along with diet behavior counseling and exercise training for 52 weeks.
干预措施: Exercise training (Behavioral)
GLP-1 RA
Participants in this group will receive semaglutide therapy along with diet behavior counseling for 52 weeks
干预措施: Semaglutide (Drug)
GLP-1 RA + Exercise
Participants in this group will receive semaglutide therapy along with diet behavior counseling and exercise training for 52 weeks.
干预措施: Semaglutide (Drug)
结局指标
主要结局
Body composition
时间窗: Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention
DEXA scan
Physical function
时间窗: Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention
Score on the Modified Physical Performance Test
次要结局
- Insulin sensitivity(Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention)
- Muscular Strength for the Seated Row exercise(Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention)
- Muscular Strength for the Leg Flexion exercise(Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention)
- Muscle mass(Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention)
- Muscle volume(Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention)
- Muscular Strength for the Chest Press exercise(Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention)
- Muscular Strength for the Leg Press exercise(Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention)
- Muscle mass(Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention)
- Muscle volume(Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention)
- Insulin sensitivity(Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention)
- Muscular Strength for the Chest Press exercise(Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention)
- Muscular Strength for the Seated Row exercise(Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention)
- Muscular Strength for the Leg Press exercise(Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention)
- Muscular Strength for the Leg Flexion exercise(Baseline, after 52 weeks of intervention, and 52 weeks after stopping the intervention)
- Neural Connectivity(Before (baseline), at the end of dose escalation (around weeks 18-20), at the end of maximal treatment (around 52 weeks), and after treatment cessation (anytime after 60 weeks) in a subset of participants randomized to the semaglutide only group.)