ASCEND-1: Lifestyle Intervention Plus Mazdutide for Weight Management

Official title

Achieving Sustained Weight Control Via Exercise, Nutrition & Drugs (Mazdutide) (ASCEND- 1 Trial)

Overview

Obesity is a chronic, progressive, and relapsing disease. Although lifestyle interventions and anti-obesity medications are effective for inducing weight loss, evidence regarding their role in long-term weight maintenance after pharmacologically induced weight reduction remains limited. In addition, the high cost and potential adverse effects of weight-loss medications restrict their prolonged use, and it is unclear whether low dose medication, intensive life style intervention or together can serve as an effective strategy for weight maintenance. This randomized controlled trial aims to evaluate the effectiveness of a 1-year intensive lifestyle intervention, a reduced dose of mazdutide (3.0 mg once weekly), or their combination in weight maintenance among individuals with obesity who have achieved initial weight loss after intensive treatment with high dose mazdutide. The study seeks to provide high-quality clinical evidence to inform long-term weight maintenance strategies after weight loss in patients with obesity.

Interventions

• Drug Mazdutide
  Mazdutide is administered subcutaneously at 3.0 mg once weekly for 52 weeks during the weight maintenance period.
• Behavioral Intensive Lifestyle Intervention
  A structured intensive lifestyle intervention including individualized dietary counseling, physical activity guidance, and behavioral modification support for 52 weeks during the weight maintenance period.

Primary outcome measures

• Percentage change of body weight [Time frame: From randomization to Week 52]

Secondary outcome measures (12)

• Change in body mass index (BMI) [Time frame: From randomization to Week 52]
• Change in waist circumference [Time frame: From randomization to Week 52]
• Change in total body fat [Time frame: From randomization to Week 52]
• Change in abdominal visceral fat area [Time frame: From randomization to Week 52]
• Change in hepatic fat content [Time frame: From randomization to Week 52]
• Change in blood pressure [Time frame: From randomization to Week 52]
• Change in serum lipid profile [Time frame: From randomization to Week 52]
• Changes in blood glucose [Time frame: From randomization to Week 52]
• Changes in insulin sensitivity [Time frame: From randomization to Week 52]
• Changes in pancreatic β-cell function [Time frame: From randomization to Week 52]
• Change in pulse wave velocity (PWV) [Time frame: From randomization to Week 52]
• Quality of sleep measured by the Pittsburgh sleep quality index (PSQI) [Time frame: From randomization to Week 52]

Eligibility criteria

Inclusion criteria

• Adult men or women aged 18 years or older;
• Simple obesity, defined as a body mass index (BMI) of 28.0-45.0 kg/m²;
• Able and willing to provide written informed consent.

Exclusion criteria

• Active pulmonary tuberculosis, malignant tumors, human immunodeficiency virus (HIV) infection, or other serious infectious or systemic diseases;
• Severe hepatic impairment (aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\] >3 times the upper limit of normal), severe renal impairment, or end-stage renal disease (estimated glomerular filtration rate \[eGFR\] <30 mL/min/1.73 m²);
• Severe cardiovascular diseases, including angina pectoris, myocardial infarction, or stroke within the past 6 months;
• Severe gastrointestinal diseases, or a history of gastrointestinal resection surgery within the past year;
• Acute or chronic pancreatitis, gallbladder disease, or pancreatic injury;
• Obesity secondary to other causes, including Cushing's syndrome, primary hypothyroidism, hypothalamic obesity, or acromegaly; drug-induced obesity, such as obesity related to the use of antipsychotic agents or glucocorticoids;
• Current smoker or habitual smoking within the past 3 months;
• Current use of other weight-loss medications or a history of bariatric surgery;
• Previously diagnosed diabetes mellitus or current use of glucose-lowering medications;
• Pregnant or breastfeeding women, or women planning pregnancy during the study period;
• Inability to complete a 2-year follow-up due to health conditions, relocation, or other reasons;
• Any other condition deemed by the investigator to make the participant unsuitable for participation in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 13 centers

• The Second Affiliated Hospital of Chongqing Medical University — Chongqing
• Fujian Provincial Hospital, Affiliated to Fuzhou University — Fuzhou
• The First Affiliated Hospital of Xiamen University — Xiamen
• Zhongnan Hospital of Wuhan University — Wuhan
• Nanjing First Hospital, Nanjing Medical University — Nanjing
• The Affiliated Suzhou Science and Technology Town Hospital of Nanjing Medical University — Suzhou
• Huadong Hospital, Fudan University — Shanghai
• Renji Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai
• … and 5 more centers

Identifiers

NCT: NCT07517042 · B2025-712

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗