Mazdutide as Adjuvant Therapy Following Sleeve Gastrectomy in Severe Obesity

N/ANot Yet RecruitingNCT07135141

Beijing Friendship Hospital256 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

256

Conditions

Severe Obesity

Interventions

After sleeve gastrectomy is preformed, mazdutide injection (pre-filled auto-injector pen) is administered subcutaneously at the same time each week at 5th month post procedure. The treatment begins with a starting dose of 2.0 mg, followed by a titration schedule increasing by 2.0 mg every 4 weeks (2.0 mg → 4.0 mg). If well-tolerated, participants reached the target maintenance dose of 6.0 mg (4.0 mg → 6.0 mg)weekly for maintenance. The protocol permits adaptive dose downgrade to 4.0 mg weekly when clinically indicated, such as intolerance. The total intervention is maintained until 48 weeks post procedure.

Sleeve gastrectomy followed with early mazdutide placebo initationDRUG

After sleeve gastrectomy is preformed, mazdutide placebo injection (pre-filled auto-injector pen) is administered subcutaneously at the same time each week at 5th month post procedure. The treatment begins with a starting dose of 2.0 mg placebo, followed by a titration schedule increasing by 2.0 mg every 4 weeks (2.0 mg → 4.0 mg). If well-tolerated, participants reached the target maintenance dose of 6.0 mg placebo(4.0 mg → 6.0 mg) weekly for maintenance. The protocol permits adaptive dose downgrade to 4.0 mg weekly when clinically indicated, such as intolerance. The total intervention is maintained until 48 weeks post procedure.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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;

Locations (14)

Beijing Friendship Hospital, Capital Medical University

Beijing, China

Beijing Hospital

Beijing, China

Peking University People's Unviersity

Beijing, China

The Third Hospital of Central South University

Changsha, China

West China Hospital of Sichuan University

Chengdu, China

The First Affiliated Hospital of Jinan University(Guangzhou Overseas Chinese Hospital)

Guangzhou, China

Qilu Hospital of Shandong University

Jinan, China

Kunming First People's Hospital

Kunming, China

Nanjing Drum Tower Hospital

Nanjing, China

Huadong Hospital affiliated to Fudan University

Shanghai, China

...and 4 more locations

Outcomes

Primary Outcomes

the rate of excess weight loss(EWL%) compared to baseline

EWL%=\[preoperative weight-post operative weight\]/\[preoperative weight -ideal body weight\]x100%, ideal weight=height²(m²)x25kg/m²