Clinical trial NCT06271200: Strategic Lifestyle Intervention for Metabolic Syndrome (SLIM-MET)
Official title: Effects of Intensive Lifestyle Interventions (ILI) on Weight Loss and Cardiometabolic Risks in Obese Adults With Metabolic Syndrome: A Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Metabolic Syndrome
Keywords: Weight loss
Intermittent fasting
10,000 steps
Mobile App
Continuous glucose monitoring (CGM)
GLP-1 receptor agonist
SGLT-2 inhibitor
Lead sponsor: National Health Research Institutes, Taiwan
Sponsor class: OTHER
Collaborators: name: Tri-Service General Hospital
name: Chang Gung Memorial Hospital
name: National Taiwan University Hospital Hsin-Chu Branch
name: Taichung Armed Forces General Hospital
First posted: 2024-02-21
Enrollment: 200
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a randomized, parallel-group, observer-masked clinical trial. A total of 200 obese participants with MetS will be enrolled. Eligible subjects will be randomly assigned to the ILI group or ULI group with an allocation ratio of 2:1.
Primary purpose: PREVENTION

Brief summary: This study is a randomized, parallel-group, observer-masked clinical trial. A total of 200 obese participants with MetS will be enrolled. Eligible subjects will be randomly assigned to the ILI group or ULI group with an allocation ratio of 2:1. The ILI group will be instructed to eat in 8 hours while fasting in 16 hours on daily basis over 24 weeks. Furthermore, enhanced daily physical activities with walking more than 10,000 steps will be implemented. The enrolled participants will be instructed to follow a diet with reduction of daily intake of 500 kcals per day. ILI group will be asked to use the Health2Sync mobile app to track self-measured outcomes and daily diet control. The investigators objectively measure step counts for participants of ILI group during 24-week intervention period using a wearable device (Fitbit Inspire 2). Participants are asked to attach the pedometer on their waist belt, except while bathing and sleeping. The ULI group will be instructed to follow habitual meal timing. In addition, all participants of both groups will receive the health education. Anthropometric, sociodemographic data, biochemical variables, and metabolic variables will be measured at baseline and during follow-up visit. DEXA and MRI of abdomen will be measured at baseline and during following up visits. The proposed trial is designed to provide 85% statistical power to detect a significant difference in changes in the metabolic syndrome severity score after reduction \> 5% body weight over 24 weeks.

After completion of the initial 24-week lifestyle intervention, which often has limited weight loss efficacy when used alone, a second-phase intervention will be conducted from week 26 to week 52. Participants in both the ILI and ULI groups will be randomly assigned in a 1:1 ratio to receive one of two evidence-based oral weight control medications: a GLP-1 receptor agonist (Rybelsus) or an SGLT-2 inhibitor (Forxiga), for a duration of 26 weeks. The ILI group will continue with the daily 8-hour time-restricted eating and 16-hour fasting regimen, along with walking more than 10,000 steps per day. This phase aims to evaluate the effects of these two medications on weight reduction and liver fat content, with or without prior 26-week intensive lifestyle intervention. After the 26-week medication intervention, all participants will be followed for an additional 52 weeks to assess the sustainability of weight loss.


Eligibility criteria: Inclusion Criteria:

* Men or women aged from ≥ 20 years to 65 years
* BMI 27.0 to 45.0 kg/m2 with metabolic syndrome by IDF definition

Exclusion Criteria:

* History of HIV, hepatitis B or C (self-report) or active pulmonary tuberculosis
* Diagnosis of type 1 or type 2 diabetes and regular taking oral or injection hypoglycemic therapy
* History of malignant tumors with active managements.
* History of medullary thyroid carcinoma or diagnosis of multiple endocrine neoplasia syndrome type 2 (MEN 2)
* Serious liver dysfunction or chronic kidney disease (aspartate aminotransferase (AST) or alanine transaminase (ALT) \> 3 times the upper limit of normal, or estimated glomerular filtration rate (eGFR) \< 30 ml/min/1.73 m2)
* History of serious cardiovascular or cerebrovascular disease (angina, myocardial infarction or stroke) in the past 6 months History of severe gastrointestinal diseases or gastrointestinal surgery in the past 6 months
* History of Cushing's syndrome, hypothyroidism, acromegaly, hypothalamic obesity without regular managements.
* History of hypersensitivity to semaglutide or any component of RYBELSUS®, or history of severe hypersensitivity reactions to Forxiga, such as anaphylaxis or angioedema.
* Taking medications affecting weight or energy intake/energy expenditure in the last 3 months, including weight loss medications, antipsychotic drugs or other medications as determined by the study physician
* Currently participating in weight loss programs or weight change in the past 3 months (\>5% current body weight)
* Women who are pregnant or plan to become pregnant
* Patients who cannot be followed for 3 years (due to a health situation or migration)
* Patients who are unwilling or unable to give informed consent

Primary outcomes:
measure: Change in the metabolic syndrome severity score (Z score) after reduction > 5% body weight from baseline to 24 weeks
timeFrame: 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Zhunan
country: Taiwan
facility: Institute of Molecular and Genomic Medicine, National Health Resesarch Institutes
state: Miaoli County
Study officials:
affiliation: National Health Research Institutes, Taiwan
name: Wayne Huey-Herng Sheu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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