Mazdutide as Adjuvant Therapy Following Sleeve Gastrectomy in Severe Obesity (SMART)

Capital Medical University

Status: Not yet enrolling

Conditions: Severe Obesity

Treatments: Drug: Sleeve gastrectomy plus early mazdutide initiation; Drug: Sleeve gastrectomy followed with early mazdutide placebo initation

Study type: Interventional

Funder types: Other

Identifiers

NCT07135141

SMART trial

Details and patient eligibility

About

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.

Enrollment: 256 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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256 participants in 2 patient groups, including a placebo group

Sleeve gastrectomy plus mazdutide group

Experimental group

Description:

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)

Treatment:

Drug: Sleeve gastrectomy plus early mazdutide initiation

Sleeve gastrectomy plus mazdutide placebo group

Placebo Comparator group

Description:

Participants will receive weekly subcutaneous injections of matched placebo at 5th month post sleeve gastrectomy

Treatment:

Drug: Sleeve gastrectomy followed with early mazdutide placebo initation