ASCEND-1: Lifestyle Intervention Plus Mazdutide for Weight Management

April 1, 2026 updated by: Shanghai Zhongshan Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

420

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Chongqing Municipality
      • Chongqing, Chongqing Municipality, China, 400000
        • Recruiting
        • The Second Affiliated Hospital of Chongqing Medical University
        • Contact:
        • Principal Investigator:
          • Dongfang Liu, MD
    • Fujian
      • Fuzhou, Fujian, China, 350000
        • Recruiting
        • Fujian Provincial Hospital, Affiliated to Fuzhou University
        • Contact:
        • Principal Investigator:
          • Gang Chen, MD
      • Xiamen, Fujian, China, 361003
        • Recruiting
        • The First Affiliated Hospital of Xiamen University
        • Contact:
        • Principal Investigator:
          • Changqin Liu, MD
    • Hubei
      • Wuhan, Hubei, China, 430000
        • Recruiting
        • Zhongnan Hospital of Wuhan University
        • Contact:
        • Principal Investigator:
          • Zhe Dai, MD
    • Jiangsu
      • Nanjing, Jiangsu, China, 210000
        • Recruiting
        • Nanjing First Hospital, Nanjing Medical University
        • Contact:
        • Principal Investigator:
          • Qian Li, MD
      • Suzhou, Jiangsu, China, 215000
        • Recruiting
        • The Affiliated Suzhou Science and Technology Town Hospital of Nanjing Medical University
        • Contact:
        • Principal Investigator:
          • Zhimin Ma, MD
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200030
        • Recruiting
        • Zhongshan Hospital, Fudan University
        • Contact:
        • Principal Investigator:
          • HUIJIE ZHANG, MD, PhD
      • Shanghai, Shanghai Municipality, China, 200000
        • Recruiting
        • Huadong Hospital, Fudan University
        • Contact:
        • Principal Investigator:
          • Bin Lu, PhD
      • Shanghai, Shanghai Municipality, China, 200000
        • Recruiting
        • Renji Hospital, Shanghai Jiao Tong University School of Medicine
        • Contact:
        • Principal Investigator:
          • Jing Ma, PhD
      • Shanghai, Shanghai Municipality, China, 200000
        • Recruiting
        • Shanghai Tenth People's Hospital, School of Medicine, Tongji University
        • Principal Investigator:
          • Shen Qu, PhD
        • Contact:
    • Sichuan
      • Luzhou, Sichuan, China, 646000
        • Recruiting
        • The Affiliated Hospital of Southwest Medical University
        • Contact:
        • Principal Investigator:
          • Yong Xu, MD
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310000
        • Recruiting
        • Zhejiang Provincial People's Hospital
        • Contact:
          • Xiaohong Wu, MD
          • Phone Number: 86-0571-85893111
          • Email: drxhwu@163.com
        • Principal Investigator:
          • Xiaohong Wu, MD
      • Wenzhou, Zhejiang, China, 325000
        • Recruiting
        • The First Affiliated Hospital of Wenzhou Medical University
        • Contact:
        • Principal Investigator:
          • Hong Zhu, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Placebo plus Intensive Lifestyle Intervention
After 16-week intensive treatment with mazdutide, participants are randomized into four different arms. In this arm, participants receive placebo once weekly plus intensive lifestyle intervention 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.
Experimental: Mazdutide
After 16-week intensive treatment with mazdutide, participants are randomized into four different arms. In this arm, participants receive mazdutide 3.0 mg once weekly for 52 weeks during the weight maintenance period.
Drug: Mazdutide
Mazdutide is administered subcutaneously at 3.0 mg once weekly for 52 weeks during the weight maintenance period.
Experimental: Mazdutide Plus Intensive Lifestyle Intervention
After 16-week intensive treatment with mazdutide, participants are randomized into four different arms. In this arm, participants receive mazdutide 3.0 mg once weekly plus intensive lifestyle intervention 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.
Drug: Mazdutide
Mazdutide is administered subcutaneously at 3.0 mg once weekly for 52 weeks during the weight maintenance period.
No Intervention: Standard Health Education (Control)
After 16-week intensive treatment with mazdutide, participants are randomized into four different arms. In this arm, participants receive standard health education only for 52 weeks during the weight maintenance period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percentage change of body weight
Time Frame: From randomization to Week 52
From randomization to Week 52

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in body mass index (BMI)
Time Frame: From randomization to Week 52
From randomization to Week 52
Change in waist circumference
Time Frame: From randomization to Week 52
From randomization to Week 52
Change in total body fat
Time Frame: From randomization to Week 52
From randomization to Week 52
Change in abdominal visceral fat area
Time Frame: From randomization to Week 52
Abdominal visceral fat area is quantified by CT scan
From randomization to Week 52
Change in hepatic fat content
Time Frame: From randomization to Week 52
Hepatic fat content is quantified by controlled attenuation parameter (CAP), measured by Fibroscan.
From randomization to Week 52
Change in blood pressure
Time Frame: From randomization to Week 52
From randomization to Week 52
Change in serum lipid profile
Time Frame: From randomization to Week 52
From randomization to Week 52
Changes in blood glucose
Time Frame: From randomization to Week 52
From randomization to Week 52
Changes in insulin sensitivity
Time Frame: From randomization to Week 52
Insulin sensitivity is assessed by HOMA-IR index
From randomization to Week 52
Changes in pancreatic β-cell function
Time Frame: From randomization to Week 52
Pancreatic β-cell function is assessed by HOMA-β index
From randomization to Week 52
Change in pulse wave velocity (PWV)
Time Frame: From randomization to Week 52
From randomization to Week 52
Quality of sleep measured by the Pittsburgh sleep quality index (PSQI)
Time Frame: From randomization to Week 52
From randomization to Week 52
Quality of life measured by the 12-item Short-Form Health Survey Questionnaire (SF-12)
Time Frame: From randomization to Week 52
From randomization to Week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Zhongshan Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2026

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

March 18, 2026

First Submitted That Met QC Criteria

April 1, 2026

First Posted (Actual)

April 8, 2026

Study Record Updates

Last Update Posted (Actual)

April 8, 2026

Last Update Submitted That Met QC Criteria

April 1, 2026

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B2025-712

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All IPD that underlie results in a publication.

IPD Sharing Time Frame

After publication.

IPD Sharing Access Criteria

IPD and supporting information will be avaible to researchers upon reasonable request (e.g. with a practical and meaningful research proposal).

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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