NCT07135141尚未招募不适用
Mazdutide as Adjuvant Therapy Following Sleeve Gastrectomy in Severe Obesity:A Multicenter, Randomized, Double-Blind, Placebo-Controlled Superiority Trial
干预措施
相关药物
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 256
- 试验地点
- 14
- 主要终点
- the rate of excess weight loss(EWL%) compared to baseline
研究概览
简要总结
The SMART study is a 96-week, multicenter, randomized, double-blind, placebo-controlled superiority clinical trial. A total of 256 severe obesity patients are randomized 1:1 to either receive the bariatric surgery plus GCG/GLP-1 dual receptor agonist group (receiving sleeve gastrectomy followed by subcutaneous injections of mazdutide weekly, with stepwise dose escalation to a maintenance dose per protocol) or the bariatric surgery plus placebo group (receiving matched procedure plus placebo injections). The primary objective is to evaluate the potential enhancing weight reduction effects of the combination therapy with bariatric surgery and mazdutide measured by the percentage change of excess weight loss.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18-70 years (inclusive), male or female;
- •BMI≥37.5 kg/m2, with or without obesity-related complications;
- •Planned to take sleeve gastrectomy
- •Understand the trial protocol, voluntarily sign the informed consent form (ICF), and agree to follow all study requirements and restrictions.
排除标准
- •Previous gastrointestinal surgery such as stomach and duodenum, or weight loss and metabolic surgery;
- •History of thyroid C-cell carcinoma, multiple endocrine neoplasia (MEN) 2A or 2B, or relevant family history;
- •ALT > 3.0 × ULN (if NAFLD is diagnosed at screening and within 6 months prior to screening, ALT ≤ 5.0 × ULN can be enrolled), or AST > 3.0 ×ULN, or total bilirubin (TBIL) > 2 × ULN
- •Estimated glomerular filtration rate eGFR < 45 mL/min/1.73 m2 using the CKD-EPI equation
- •Chronic anemia：Hemoglobin < 110 g/L (males) or < 100 g/L (females)；
- •Have the following 12-lead electrocardiogram (ECGs) abnormalities at screening(<50 beats/min or >100 beats/min), 2nd or 3rd degree atrioventricular block, long QT syndrome or QTcF > 450 ms (males), QTcF > 470 ms (females), left or right bundle branch block, pre-excitation syndrome, or other significant arrhythmia (except sinus arrhythmia);
- •Acute hyperglycemic/hypoglycemic events within 1 year, including:
- •diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and hypoglycemic coma, etc;
- •Participants with previous severe myocardial infarction, stroke, acute and chronic heart failure, cardiac procedure such as percutaneous coronary intervention, coronary artery bypass grafting, or are not suitable for participation in this study after the investigator's assessment;
- •Previous or confirmed mental illness at screening/randomization phase[Previous moderate to severe depressionPHQ questionnaire (Depression Screening Scale) ≥ 15 points, C-SSRS questionnaire (Columbia Suicide Severity Scale) category 4 or 5 at screening or randomization, or "Yes" in suicidal behavior or suicidal ideation];
- •Previous specific infectious diseases, incl. acquired immunodeficiency syndrome, viral hepatitis B, viral hepatitis C, etc;
- •End-stage disease with an expected survival of less than 5 years or previous/current malignancy;
- •Use of GLP-1 receptor (GLP-1R) agonists or GLP-1R/GCGR agonists or GIPR/GLP-1R agonists or GIPR/GLP-1R/GCGR agonists within three months prior to screening;
- •History of alcohol or drug abuse at screening;
- •History of specific drugs use beyond 2 times, incl. moderate anticholinergics, antiparkinsonians, antiepileptic drugs, antipsychotics, benzodiazepines and sedatives, morphine and narcotic analgesics, stimulant drugs, medical marijuana, marijuana, and cannabidiol, etc.;
- •Pregnant or lactating females, males or females of childbearing potential who are not willing to use contraception throughout the study and for 8 weeks after the end of the study;
- •Having participated in other clinical investigators who have a conflict of interest with this study;
- •The investigator suspects that the participant may be allergic to ingredients in the study drug or drugs of the same class;
研究组 & 干预措施
Sleeve gastrectomy plus mazdutide group
Experimental
Participants will receive weekly subcutaneous injections of mazdutide at 5th month post sleeve gastrectomy(starting at 2.0 mg, with stepwise dose escalation to a target maintenance dose of 6.0 mg and optional adaptive downgrade to 4.0 mg if necessary)
干预措施: Sleeve gastrectomy plus early mazdutide initiation (Drug)
Sleeve gastrectomy plus mazdutide placebo group
Placebo Comparator
Participants will receive weekly subcutaneous injections of matched placebo at 5th month post sleeve gastrectomy
干预措施: Sleeve gastrectomy followed with early mazdutide placebo initation (Drug)
结局指标
主要结局
the rate of excess weight loss(EWL%) compared to baseline
时间窗: At 48th week post procedure
EWL%=\[preoperative weight-post operative weight\]/\[preoperative weight -ideal body weight\]x100%, ideal weight=height²(m²)x25kg/m²
次要结局
- Assessing the change in BMI(kilogram/square meter, kg/m²） classification compared to baseline(Based on the BMI classification in Chinese adiposity diagnosis and treatment guideline 2024)(At 48th week post procedure)
- Assessing the rate of total body weight loss(TBWL%) compared to baseline(At 48th week post procedure)
- Assessing the change of waist circumference(centimeter, cm) compared to baseline(at 48th week post procedure)
- Assessing the change of hip circumference(centimeter, cm) compared to baseline(At 48th week post procedure)
- Assessing the change of blood pressure(incl. systolic blood pressure and diastolic blood pressure) compared to baseline（Hydrargyrum, mmHg）(At 48th week post procedure)
- Assessing the percentage change(%) of triglyceride(TG), low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC) or high-density lipoprotein cholesterol(HDL-C) compared to baseline(At 48th week post procedure)
- Assessing the change of aspartate transaminase(AST) or alanine aminotransferase(ALT) compared to baseline(At 48th week post procedure)
- Assessing the change(%) of serum uric acid compared to baseline(At 48th week post procedure)
- Assessing the change of nutrition status (incl. albumin, victamin B12, folic acid or serum iron and so forth) compared to baseline(At 48th week post procedure)
- Assessing the change of body weight related life quality(IWQOL-Lite) , upper GI symptom scale(GERDQ) or overall life quality scale(SF-36) compared to baseline(At 48th week post procedure)
- Assessing the rate(%) of procedure-related or drug-related complications, re-admission, or major cardiovascular adverse events(At 48th week post procedure)
- Assessing the rate(%) of body weight regain among participants(At 96th week post procedure)
- Assessing the percentage change（%） of body fat or fat-free mass compared to baseline(At 48th week post procedure)
- Assessing the percentage change（%） of liver fat content or pancreatic fat content compared to baseline(At 48th week post procedure)
研究者
Zhongtao Zhang
Professor, Vice president of hospital
Beijing Friendship Hospital
研究点 (14)
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