Impact of Semaglutide Withdrawal on Cardiometabolic Profile and Physiology of Energy Balance: a Randomized Controlled Trial Comparing Gradual Dose Reduction With Immediate Treatment Cessation.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 98
- 试验地点
- 1
- 主要终点
- Differences in changes in body weight between each study group
研究概览
简要总结
Semaglutide is a medication from the class of drugs called glucagon-like peptide-1 agonists that promote weight loss. There is little clinical data on the best strategy to achieve weight maintenance following weight reduction induced by semaglutide. For people who need to discontinue treatment, it is unknown whether the weight regain, its accompanied health benefits could be ameliorated with a gradual reduction in semaglutide. The investigators will study if a gradual reduction of semaglutide is associated with different heart risk profile and hormones involved in energy regulation as compared to immediate treatment cessation.
详细描述
It is known that semaglutide induces a supra-physiologic agonism of GLP-1 receptors on central nervous system receptors associated with hedonic eating which likely promotes a homeostatic response (i.e. adaptation) related to appetite control. This concept raises the question of whether a gradual de-escalation of GLP-1RA could ameliorate the tendency for weight regain/cardiometabolic deterioration and compensatory changes in energy balance regulation following cessation of treatment.Thus, the investigators propose an open-label, parallel-arm, randomized controlled trial to determine whether a gradual dose reduction in semaglutide prior to complete discontinuation is associated with differential changes in weight and cardiometabolic profile (blood pressure homeostasis and energy balance regulatory hormones) as compared to immediate treatment cessation in individuals living with obesity without pre-existing cardiovascular disease who are receiving semaglutide for weight management.
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women with previously diagnosed BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 and adiposity-related complications (such as osteoarthritis, nonalcoholic liver disease, sleep apnea, and hypertension) without preexisting cardiovascular disease or type 2 diabetes.
- •Age 18 - 75 years inclusive
- •Ongoing weight-loss treatment consisting of weekly subcutaneous semaglutide at minimum dose of 1 mg/weekly with documented weight reduction of at least 10% of pre-treatment body weight
- •Stable weight over past 12 weeks (less than 5% change in body weight) (self-reported)
- •Ability to read and understand English
排除标准
- •Previously diagnosed cardiovascular disease defined as previous myocardial infarction, previous stroke, or symptomatic peripheral arterial disease.
- •Currently pregnant or lactating
- •Previously diagnosed type 2 diabetes
- •Use of any other pharmacological treatment for weight-loss
- •Previous surgical treatment for weight loss such as gastric bypass or gastric band
- •Any history of eating disorder
- •Renal dysfunction as evidenced by estimated glomerular filtration rate < 25 ml/min by CKD-EPI Creatinine Equation
- •New York Heart Association class II-IV heart failure
- •Hepatic disease considered to be clinically significant (includes jaundice, chronic hepatitis, or previous liver transplant) or transaminases >2.5X the upper limit of normal
- •Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy within the previous 5 years (with the exception of basal cell skin cancer)
- •Personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2
- •Any other factor likely to limit adherence to the study, in the opinion of the investigators
研究组 & 干预措施
Gradual dose reduction of semaglutide
Participants will reduce semaglutide dosage by 25% every 4-weeks until complete treatment cessation at week 16
干预措施: Gradual dose reduction of semaglutide (Drug)
Cessation of semaglutide
Participants will discontinue treatment at once at week 16
干预措施: Abrupt cessation of semaglutide (Drug)
结局指标
主要结局
Differences in changes in body weight between each study group
时间窗: 32 weeks
Differences in body weight change (%) between baseline visit 1 (semaglutide discontinuation) and 5 (16-weeks after complete semaglutide withdrawal) will be compared between the study groups
次要结局
- Differences in 24-h systolic BP levels between each study group(32 weeks)
- Differences in fasting ghrelin between each study group(32 weeks)