Weight regain after intentional short-term weight loss is a common challenge. It often undermines the long-term benefits of obesity treatment. This study is a multi-center 2-arm randomized controlled trial across six regions in China, specifically targeting overweight or obese adults who have recently achieved a short-term weight reduction (≥5% of body weight). The trial will evaluate whether a 10-hour daily Time-Restricted Eating (TRE) regimen can more effectively prevent weight regain compared to standard weight maintenance counseling alone. Both the intervention and control groups will receive the same frequency and intensity of nutritional counseling for weight maintenance; the only difference is that the TRE group will be instructed to confine their daily eating to a self-selected 10-hour window, while the control group has no eating window restriction. In addition to the primary outcome of weight regain, the study will explore potential mechanisms underlying the effects of TRE and assess secondary outcomes including changes in body composition, metabolic health, and quality of life. This study recruits participants from six distinct regions across Eastern, Western, Southern, Northern, and Central China to enhance national representativeness. The study is divided into two phases: the first phase is a 2-month weight loss run-in phase (the screening phase), during which participants will receive standardized lifestyle and diet guidance from trained dietitians. Those who achieve at least a 5% loss of initial body weight by the end of this phase-and maintain a stable weight for approximately three weeks-will proceed to the second phase. In the second phase, participants will be randomly assigned to one of two arms for a 12-month weight maintenance intervention. The Control Arm will receive periodic weight-management nutritional counseling without any eating time restriction, while the TRE Intervention Arm will receive the same guidance plus instructions to follow a daily 10-hour time-restricted eating schedule. This design ensures both groups receive equivalent dietary and lifestyle support, with TRE as the key differential strategy. Following the 12-month intervention phase, participants will be followed for an additional 12 months (without active intervention) to observe longer-term weight outcomes. Data will be collected at multiple time points: baseline (before the weight loss phase), 2 months (end of the weight loss phase and prior to the start of the maintenance phase), 5 months, 8 months, 14 months (end of the weight maintenance phase), as well as 20 months and 26 months (during the post-intervention follow-up). Key outcomes include changes in body weight (to assess weight regain or maintenance), body composition, metabolic health indicators (e.g. blood glucose, lipids), and quality of life measures. To monitor dietary behaviors, participants will be asked to upload meal photos via a designated mobile application with automatic time-stamping, which will be used to assess eating timing and adherence to the prescribed eating window. Body weight will be measured once weekly using Bluetooth-enabled smart scales. To explore potential mechanisms of action, biospecimens (blood and stool) will be collected at baseline, 2 months, 8 months, and 14 months for analysis. In addition, Continuous Glucose Monitoring (CGM) will be performed in a randomly selected subsample of 200 participants (100 from each group) using a standardized device for 14 consecutive days at months 2, 8, and 14. These data will be used to evaluate glycemic stability and adherence to the assigned eating window. Real-time CGM readings will not be disclosed to participants and will not be used to guide individual-level interventions.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
500
Participants will receive a standardized 30-45 minute weight maintenance nutrition education session at the time of randomization, covering principles of balanced dietary intake, reduction of salt, oil, and added sugar, adequate hydration. Thereafter, monthly 15-minute follow-up sessions will be delivered by trained dietitians, matched in frequency and content to those provided in the intervention arm. No temporal restriction will be imposed on eating behaviors. Participants will document meal intake via a mobile application using photograph-based entries with automated time-stamping and will record body weight weekly using Bluetooth-enabled digital scales. To ensure data accuracy, quality control will include twice-monthly brief telephone interviews for unannounced 24-hour dietary recalls.
In addition to receiving the same frequency and content of standardized nutritional counseling as the control group, participants will be instructed to confine all caloric intake to a self-selected 10-hour daily eating window. Outside of this window, only non-caloric beverages (e.g., water, unsweetened tea, black coffee) are permitted. Up to one exception day per week is allowed, during which intake may fall outside the designated window but must still be recorded. Dietary intake will be logged through a mobile application utilizing meal photographs with automated time-stamping; body weight will be recorded weekly using Bluetooth-enabled digital scales. As with the control group, participants will receive twice-monthly unannounced 24-hour dietary recalls and phone interviews to verify dietary records and ensure data quality.
The Fifth Medical Center of Chinese PLA General Hospital
Beijing, Beijing Municipality, China
Army Medical Center of PLA
Chongqing, Chongqing Municipality, China
Shenzhen People's Hospital
Shenzhen, Guangdong, China
The First Affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang, China
Harbin Medical University
Harbin, Heilongjiang, China
The Second Affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang, China
The Second Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi, China
The Affiliated Hospital of Qingdao University
Qingdao, Shandong, China
Weifang People's Hospital
Weifang, Shandong, China
Chengdu Seventh People's Hospital
Chengdu, Sichuan, China
Weight change
The measurement will be conducted using the InBody570 bioelectrical impedance analyzer
Time frame: At 0 (baseline), 2, 5, 8, 14, 20 and 26 months.
Percentage of Participants Maintaining ≥5% Weight Loss from Baseline
The proportion of participants who achieve and sustain at least a 5% reduction in their baseline body weight by the end of the study. A participant is considered successful if their weight at 12 months is ≥5% lower than their weight at baseline.
Time frame: At 14, 20, and 26 months
Change in waist circumference
Measurements will be taken using the same model of standardized soft measuring tape.
Time frame: At 0 (baseline), 2, 5, 8, 14, 20 and 26 months.
Change in hip circumference
Measurements will be taken using the same model of standardized soft measuring tape.
Time frame: At 0 (baseline), 2, 5, 8, 14, 20 and 26 months.
Change in body composition
The body composition of patients will be measured using the InBody570 bioelectrical impedance analyzer, assessing key parameters (e.g., body mass index \[BMI\], fat mass \[FM\], fat-free mass \[FFM\], skeletal muscle mass \[SMM\], visceral fat area \[VFA\], total body water \[TBW\], extracellular water \[ECW\], intracellular water \[ICW\], basal metabolic rate \[BMR\], waist-hip ratio \[WHR\], and phase angle \[PhA\]).
Time frame: At 0 (baseline), 2, 5, 8, 14, 20 and 26 months.
Change in blood pressure (systolic pressure and diastolic pressure)
Measurements will be taken using the same brand and model of precision blood pressure monitor.
Time frame: At 0 (baseline), 2, 5, 8, 14, 20 and 26 months.
Change in heart rate
Measurements will be taken using the same brand and model of precision blood pressure monitor.
Time frame: At 0 (baseline), 2, 5, 8, 14, 20 and 26 months.
Change in handgrip strength
The handgrip strength of patients will be assessed using handgrip dynamometers of the same brand and model.
Time frame: At 0 (baseline), 2, 5, 8, 14, 20 and 26 months.
Changes in blood transcriptomics
Transcriptomic sequencing will be performed on blood samples collected from the patients to observe changes in blood transcriptional levels.
Time frame: At 0 (baseline), 2, 8 and 14 months.
Changes in metabolomics in serum and feces
Metabolomic sequencing will be performed on serum and fecal samples collected from the patients to observe changes in metabolic levels.
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in quality of sleep measured by the Pittsburgh Sleep Quality Index (PSQI)
The sleep quality of each patient will be evaluated by the Pittsburgh Sleep Quality Index (PSQI), with scores ranging from 0 to 21, with higher scores indicating poorer sleep quality
Time frame: At 0 (baseline), 2, 5, 8, 14, 20 and 26 months.
Change in appetite states measured by the Electronic Visual Analogue Scale (eVAS)
Subjective appetite states were assessed using the Electronic Visual Analogue Scale (eVAS), with scores ranging from 0 to 100 for each dimension (hunger, fullness, desire to eat, and estimated food intake). Higher scores indicate stronger sensations.
Time frame: At 0 (baseline), 2, 5, 8, 14, 20 and 26 months.
The DISC Personality Assessment
The DISC Personality Assessment evaluates four dimensions: Dominance (D), Influence (I), Steadiness (S), and Conscientiousness (C), with higher scores indicating stronger behavioral tendencies in each domain.
Time frame: At 0 (baseline)
Change in quality of life measured by the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) Questionnaire
Health-related quality of life was assessed using the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire, with scores ranging from 0 to 100 across five domains (Physical Function, Self-Esteem, Sexual Life, Public Distress, and Work Life). Higher scores indicate better weight-related quality of life.
Time frame: At 0 (baseline), 2, 8, 14 and 26 months.
Change in fasting blood glucose
Blood samples from the patients will be tested for fasting blood glucose levels.
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in fasting insulin
Blood samples from the patients will be tested for fasting insulin levels.
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in glycated hemoglobin (HbA1c)
Blood samples from the patients will be tested for glycated hemoglobin (HbA1c) levels.
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum creatinine level
Serum creatinine level will be measured from blood samples using an enzymatic method. Results will be reported in micromoles per liter (μmol/L).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in blood urea nitrogen level
Blood urea nitrogen level will be measured from blood samples using the urease method. Results will be reported in millimoles per liter (mmol/L).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum uric acid level
Serum uric acid level will be measured from blood samples using the uricase-ultraviolet method. Results will be reported in micromoles per liter (μmol/L).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Alanine Aminotransferase (ALT) level
Serum alanine aminotransferase (ALT) level will be measured from blood samples using a rate method. Results will be reported in units per liter (U/L).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Aspartate Aminotransferase (AST) level
Serum aspartate aminotransferase (AST) level will be measured from blood samples using a rate method. Results will be reported in units per liter (U/L).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in Aspartate aminotransferase to Alanine aminotransferase ratio (AST/ALT)
The AST/ALT ratio (De Ritis ratio) will be calculated from the measured values of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Results will be reported as a ratio.
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Gamma-Glutamyl Transferase (GGT) level
Serum gamma-glutamyl transferase (GGT) level will be measured from blood samples using a rate method. Results will be reported in units per liter (U/L).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Total Protein (TP) level
Serum total protein (TP) level will be measured from blood samples using the biuret method. Results will be reported in grams per liter (g/L).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Albumin (ALB) level
Serum albumin (ALB) level will be measured from blood samples using the bromocresol green (BCG) method. Results will be reported in grams per liter (g/L).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Globulin (GLOB) level
Serum globulin (GLOB) level will be calculated by subtracting the measured serum albumin value from the measured serum total protein value. Results will be reported in grams per liter (g/L).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in Albumin to Globulin ratio (A/G)
The Albumin to Globulin ratio (A/G) will be calculated from the measured values of serum albumin and calculated globulin. Results will be reported as a ratio.
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in depression symptoms as measured by the Self-Rating Depression Scale (SDS)
Depression symptoms will be assessed using the Self-Rating Depression Scale (SDS). The SDS total score ranges from 20 to 80, with higher scores indicating more severe depressive symptoms (worse outcome).
Time frame: At 0 (baseline), 2, 8, 14 and 26 months.
Change in anxiety symptoms as measured by the Self-Rating Anxiety Scale (SAS)
Anxiety symptoms will be assessed using the Self-Rating Anxiety Scale (SAS). The SAS total score ranges from 20 to 80, with higher scores indicating more severe anxiety symptoms (worse outcome).
Time frame: At 0 (baseline), 2, 8, 14 and 26 months.
Change in serum Total Cholesterol (TC) level
Serum concentration of Total Cholesterol (TC) will be measured from blood samples using the cholesterol oxidase method. Results will be reported in millimoles per liter (mmol/L).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Triglycerides (TG) level
Serum concentration of Triglycerides (TG) will be measured from blood samples using an enzymatic method. Results will be reported in millimoles per liter (mmol/L).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum High-Density Lipoprotein Cholesterol (HDL-C) level
Serum concentration of High-Density Lipoprotein Cholesterol (HDL-C) will be measured from blood samples using an enzymatic method. Results will be reported in millimoles per liter (mmol/L).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Low-Density Lipoprotein Cholesterol (LDL-C) level
Serum concentration of Low-Density Lipoprotein Cholesterol (LDL-C) will be measured from blood samples using an enzymatic method. Results will be reported in millimoles per liter (mmol/L).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Interleukin-1 beta (IL-1β) level
Serum concentration of Interleukin-1 beta (IL-1β) will be measured from blood samples using a standardized multiplex immunoassay. Results will be reported in picograms per milliliter (pg/mL).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Interleukin-6 (IL-6) level
Serum concentration of Interleukin-6 (IL-6) will be measured from blood samples using a standardized multiplex immunoassay. Results will be reported in picograms per milliliter (pg/mL).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Interleukin-8 (IL-8) level
Serum concentration of Interleukin-8 (IL-8) will be measured from blood samples using a standardized multiplex immunoassay. Results will be reported in picograms per milliliter (pg/mL).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Interleukin-10 (IL-10) level
Serum concentration of Interleukin-10 (IL-10) will be measured from blood samples using a standardized multiplex immunoassay. Results will be reported in picograms per milliliter (pg/mL).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Tumor Necrosis Factor-alpha (TNF-α) level
Serum concentration of Tumor Necrosis Factor-alpha (TNF-α) will be measured from blood samples using a standardized multiplex immunoassay. Results will be reported in picograms per milliliter (pg/mL).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Transforming Growth Factor-beta (TGF-β) level
Serum concentration of Transforming Growth Factor-beta (TGF-β) will be measured from blood samples using a standardized multiplex immunoassay. Results will be reported in picograms per milliliter (pg/mL).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) level
Serum concentration of Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) will be measured from blood samples using a standardized multiplex immunoassay. Results will be reported in picograms per milliliter (pg/mL).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Leptin level
Serum concentration of Leptin will be measured from blood samples using a standardized immunoassay. Results will be reported in nanograms per milliliter (ng/mL).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Adiponectin level
Serum concentration of Adiponectin will be measured from blood samples using a standardized immunoassay. Results will be reported in micrograms per milliliter (μg/mL).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum C-reactive Protein (CRP) level
Serum concentration of C-reactive Protein (CRP) will be measured from blood samples using an immunoturbidimetric assay. Results will be reported in milligrams per liter (mg/L).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Tumor Necrosis Factor-alpha-induced protein 3 (TNFAIP3/A20) level
Serum concentration of Tumor Necrosis Factor-alpha-induced protein 3 (TNFAIP3/A20) will be measured from blood samples using a standardized enzyme-linked immunosorbent assay (ELISA). Results will be reported in nanograms per milliliter (ng/mL).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in plasma Lipopolysaccharide (LPS) level
Plasma concentration of Lipopolysaccharide (LPS) will be measured from blood samples using a commercial enzyme-linked immunosorbent assay (ELISA) kit. Results will be reported in endotoxin units per milliliter (EU/mL).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Lipopolysaccharide-Binding Protein (LBP) level
Serum concentration of Lipopolysaccharide-Binding Protein (LBP) will be measured from blood samples using a commercial enzyme-linked immunosorbent assay (ELISA) kit. Results will be reported in micrograms per milliliter (μg/mL).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Resolvin D1 (RvD1) level
Serum concentration of Resolvin D1 (RvD1) will be measured from blood samples using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results will be reported in picograms per milliliter (pg/mL).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in serum Resolvin E1 (RvE1) level
Serum concentration of Resolvin E1 (RvE1) will be measured from blood samples using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results will be reported in picograms per milliliter (pg/mL).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Daily Energy and Macronutrient Intake
Total energy intake and macronutrient distribution (percentage of energy from carbohydrates, fat, and protein) will be assessed at each time point using three non-consecutive 24-hour dietary recalls. Results will be reported in kilocalories (kcal) for energy and percentage points (%) for macronutrient distribution.
Time frame: At 0 (baseline), 2, 5, 8 14, 20, and 26 months.
Within-individual variability in daily interstitial glucose (SD)
Variability in daily interstitial glucose will be assessed using the standard deviation (SD) of mean daily glucose values across the continuous glucose monitoring (CGM) period. This metric quantifies day-to-day fluctuation in glucose concentration. Results will be reported in milligrams per deciliter (mg/dL).
Time frame: At months 2, 8, and 14. Each assessment will be conducted using continuous glucose monitoring (CGM) over a consecutive 14-day period.
Within-individual variability in daily interstitial glucose (CV)
Variability in daily interstitial glucose will be assessed using the coefficient of variation (CV), calculated as the standard deviation divided by the mean glucose level across the CGM period. This metric quantifies relative variability in glucose concentration. Results will be reported as a percentage (%).
Time frame: At months 2, 8, and 14. Each assessment will be conducted using continuous glucose monitoring (CGM) over a consecutive 14-day period.
Mean amplitude of glycemic excursions (MAGE)
Variability in daily interstitial glucose will be assessed using mean amplitude of glycemic excursions (MAGE), which represents the average magnitude of significant glucose fluctuations across the CGM period. This metric quantifies short-term glycemic variability. Results will be reported in milligrams per deciliter (mg/dL).
Time frame: At months 2, 8, and 14. Each assessment will be conducted using continuous glucose monitoring (CGM) over a consecutive 14-day period.
Percentage of monitoring time with interstitial glucose 70-140 mg/dL (TIR)
Glycemic control will be assessed as the percentage of total monitoring time spent in the target glucose range of 70-140 mg/dL during CGM. This metric quantifies the proportion of time glucose values remain within the predefined range. Results will be reported as a percentage (%).
Time frame: At months 2, 8, and 14. Each assessment will be conducted using continuous glucose monitoring (CGM) over a consecutive 14-day period.
Change in postprandial glucose excursion
The magnitude of postprandial glucose excursion will be assessed using continuous glucose monitoring (CGM), calculated as the difference between the peak interstitial glucose concentration and the pre-prandial level following main meals. Glucose data will be time-synchronized with self-reported dietary intake logs. Results will be reported in millimoles per liter (mmol/L).
Time frame: At 2, 8, and 14 months.
Change in postprandial time above range (pTAR)
The percentage of time that interstitial glucose concentrations exceed 10.0 mmol/L during the 3-hour postprandial period will be assessed using continuous glucose monitoring (CGM). Glucose data will be time-synchronized with self-reported dietary intake logs. Results will be reported as a percentage of the postprandial monitoring period (%).
Time frame: At 2, 8, and 14 months.
Change in thyroid-stimulating hormone (TSH)
Serum TSH levels will be measured from blood samples. Results will be reported in milli-international units per liter (mIU/L).
Time frame: At 0 (baseline), 2, 8 and 14 months.
Change in free thyroxine (FT4)
Serum FT4 levels will be measured from blood samples. Results will be reported in picomoles per liter (pmol/L).
Time frame: At 0 (baseline), 2, 8 and 14 months.
DNA Methylation Patterns
Genome-wide DNA methylation profiles will be assessed using peripheral blood samples collected at specified time points. Changes in DNA methylation will be explored as potential mechanistic biomarkers mediating the effects of time-restricted eating on metabolic health and weight regulation.
Time frame: At 0 (baseline), 2, 8, and 14 months.
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