An Intervention Study Investigating Effect of Dietary Protein Supplementation on Body Weight and Metabolic Homeostasis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Change in Body Weight (kg) from Baseline to Week 12
研究概览
简要总结
This study is a randomized clinical trail with a parallel design, involving 120 overweight/obese (body-mass index, BMI ≥ 24 kg/m²) participants and 20 normal-weight participants. Overweight/obese participants will be randomly allocated to one of three groups: 1) calorie restricted balanced diet (CRD)group; 2) CRD + semaglutide group; or 3) CRD + segaglutide with protein supplementation. Through a 3-month weight loss intervention and 6-month follow-up, this study aims to investigate the effects of dietary protein supplementation combined with semaglutide on weight loss, energy and glucose and lipid metabolism, muscle loss, and weight regain. Additionally, the study will explore key factors affecting intervention efficacy, including obesity phenotypes, gut microbiota profiles, genetic backgrounds, and lifestyle factors, to provide evidence for optimizing individualized intervention strategies.
详细描述
The primary objective of this study is to determine whether adding dietary protein supplementation to GLP 1 receptor agonist (GLP-1RA, semaglutide) therapy enhances weight loss efficacy, improves energy and glucose-lipid metabolism, mitigates muscle loss, and prevents weight regain. Investigators will also explore key modifiers of treatment response-including obesity phenotype, gut microbiota composition, genetic background, and lifestyle factors-to provide an evidence base for personalized interventions.
Investigators will enroll 120 adults with overweight or obesity (BMI ≥ 24 kg/m²) and randomly assign them (1 : 1 : 1) to one of three 3 month interventions:
- CRD: calorie restricted balanced diet;
- CRD + GLP-1RA: CRD plus semaglutide;
- CRD + GLP-1RA + HP: CRD plus semaglutide and 30 g/day of dietary protein supplement.
Baseline and post intervention assessments will include questionnaires; evaluations of diet, physical activity, and sleep patterns; physical examination (height, weight, waist and hip circumference, blood pressure, pulse); body composition analysis; hepatic fat and fibrosis imaging; facial skin phenotyping; 14 day continuous glucose monitoring; 14 day accelerometer based sleep and activity monitoring; stool and urine collection; and a mixed-macronutrient tolerance test (MMTT) performed in a metabolic chamber.
During the MMTT, participants consume a standardized beverage containing 126.5 g glucose, 30.67 g fat, and 34.5 g protein. Blood samples are collected at 0, 0.5, 1, 2, 3, 4, and 5 hours to characterize post prandial dynamics of energy metabolism, routine clinical biomarkers, and metabolomic profiles. Throughout the intervention, dietary intake is recorded via a mobile application, and body weight changes are tracked with an application linked smart scale.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged 20 to 50 years.
- •Normal-weight participants: 18.5 kg/m² ≤ Body Mass Index (BMI) < 24 kg/m².
- •Overweight or obese participants:
- •BMI ≥ 28 kg/m², or 24 kg/m² ≤ BMI < 28 kg/m² and a clinical diagnosis meeting semaglutide treatment indications (e.g., hyperglycemia, hypertension, dyslipidemia, fatty liver, obstructive sleep apnea, cardiovascular disease, etc.).
- •Willingness to participate in this study and provide signed informed consent.
排除标准
- •Abnormal metabolic indicators (meeting any one of the following criteria is grounds for exclusion):
- •1. Normal weight (18.5 kg/m² ≤ BMI < 24 kg/m²):
- •Waist circumference ≥ 90 cm for men or ≥ 85 cm for women.
- •Fasting glucose ≥ 6.1 mmol/L or 2-hour postprandial glucose ≥ 7.8 mmol/L, or a confirmed diagnosis of diabetes.
- •Systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85 mmHg, or currently under antihypertensive treatment.
- •Fasting triglycerides (TG) ≥ 1.7 mmol/L; high-density lipoprotein cholesterol (HDL-C) < 0.9 mmol/L in men or < 1.0 mmol/L in women.
- •2. Overweight or obese (BMI ≥ 24 kg/m²):
- •Fasting plasma glucose > 11.1 mmol/L or HbA1c > 9%, or previously diagnosed diabetes, or currently using insulin or any antidiabetic medication.
- •Blood pressure ≥ 160/100 mmHg, or clinically diagnosed stage 2 or stage 3 (moderate or severe) hypertension, or currently under antihypertensive treatment.
- •Use of lipid-lowering drugs (e.g., fibrates, bile acid sequestrants, statins, PCSK9 inhibitors) within the past 3 months, or TG ≥ 5.7 mmol/L, or LDL ≥ 4.9 mmol/L.
- •Pregnancy or lactation.
- •Self-reported weight change of more than 5 kg within the 90 days prior to screening.
- •Use of antibiotics, antimicrobials, or anti-inflammatory/analgesic salicylates (e.g., aspirin) within the 3 months prior to screening for 3 days or more.
- •Use of estrogen therapy or other hormonal medications within the past 6 months.
- •Use of GLP-1 receptor agonists or probiotics within the past 3 months.
- •Heavy alcohol consumption (females > 40 g/day, approximately 250 mL of huangjiu [yellow rice wine], or 1000 mL of beer, or 100 mL of liquor per day; males > 80 g/day).
- •Severe liver or kidney dysfunction (ALT, AST, or serum creatinine exceeding 3 times the upper limit of normal, UACR ≥ 30 mg/g, or eGFR < 60 mL/min).
- •Gastrointestinal diseases affecting digestion and absorption (e.g., severe diarrhea, severe constipation, severe inflammatory bowel disease, peptic ulcer, gallstones, cholecystitis).
- •Underwent surgery within the past year (excluding appendectomy or hernia repair).
- •Severe cardiovascular or cerebrovascular diseases (e.g., heart failure, myocardial infarction, stroke, acute myocarditis, severe arrhythmia, or receiving interventional therapy).
- •Presence of metallic implants such as a cardiac stent or pacemaker.
- •Cancer or having received radiation or chemotherapy within the past 5 years.
- •Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia, or a personal history of hyperthyroidism or hypothyroidism.
- •Chronic or acute pancreatitis.
- •Positive hepatitis B surface antigen (HBsAg), active tuberculosis, HIV, or other infectious diseases.
- •Currently participating in another clinical study or having done so within the past 3 months.
- •Claustrophobia.
- •Any psychiatric disorder such as attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, or epilepsy (including current use of antiepileptic medications), or use of antidepressant medications.
- •Inability to read, write, operate a smartphone, or perform daily activities independently.
研究组 & 干预措施
CRD
They will receive calorie restricted balanced diet and placebo
干预措施: Calorie-restricted balanced diet (Behavioral)
CRD+GLP-1RA
They will receive calorie restricted balanced diet and semaglutide
干预措施: Calorie-restricted balanced diet (Behavioral)
CRD+GLP-1RA+HP
They will receive calorie restricted balanced diet, semaglutide, and 30g/day of dietary protein supplementation
干预措施: Calorie-restricted balanced diet (Behavioral)
CRD+GLP-1RA+HP
They will receive calorie restricted balanced diet, semaglutide, and 30g/day of dietary protein supplementation
干预措施: semaglutide (Drug)
CRD+GLP-1RA
They will receive calorie restricted balanced diet and semaglutide
干预措施: semaglutide (Drug)
CRD+GLP-1RA+HP
They will receive calorie restricted balanced diet, semaglutide, and 30g/day of dietary protein supplementation
干预措施: Dietary protein supplementation (Dietary Supplement)
Healthy Comparators
They will receive general lifestyle and nutritional education.
干预措施: General lifestyle and nutritional education (Behavioral)
结局指标
主要结局
Change in Body Weight (kg) from Baseline to Week 12
时间窗: Baseline and Week 12
The change between the baseline and after 12-week intervention. Weight will be assessed using a Seca-255 scale (ScalesGalore).
次要结局
- Change in Energy Expenditure Rate (kcal/minute) from Baseline to Week 12(Baseline and Week 12)
- Change in Respiratory Quotient from Baseline to Week 12(Baseline and Week 12)
- Change in Fat Oxidation Rate (g/minute) from Baseline to Week 12(Baseline and Week 12)
- Change in Carbohydrate Oxidation Rate (g/minute) from Baseline to Week 12(Baseline and Week 12)
- Change in Waist Circumference (cm) from Baseline to Week 12(Baseline and Week 12)
- Change in Hip Circumference (cm) from Baseline to Week 12(Baseline and Week 12)
- Change in Fat-free Mass (kg) From Baseline to Week 12(Baseline (Week 0) and Week 12)
- Change in Fat Mass (kg) From Baseline to Week 12(Baseline (Week 0) and Week 12)
- Change in Controlled Attenuation Parameter (CAP, dB/m) from Baseline to Week 12(Baseline and Week 12)
- Change in Systolic Blood Pressure (mmHg) from Baseline to Week 12(Baseline and Week 12)
- Change in Diastolic Blood Pressure (mmHg) from Baseline to Week 12(Baseline and Week 12)
- Change in Heart Rate (beats/minute) from Baseline to Week 12(Baseline and Week 12)
- Change in Fasting Glucose (mmol/L) from Baseline to Week 12(Baseline and Week 12)
- Change in Glucose Incremental AUC (mmol·min/L) from Baseline to Week 12(Baseline and Week 12)
- Change in HbA1c (%) from Baseline to Week 12(Baseline and Week 12)
- Change in Fasting Insulin (µIU/mL) from Baseline to Weel 12(Baseline and Week 12)
- Change in Insulin Incremental AUC (µIU·min/mL) from Baseline to Weel 12(Baseline and Week 12)
- Change in Fasting C-peptide (ng/mL) from Baseline to Week 12(Baseline and Week 12)
- Change in C-peptide Incremental AUC (ng·min/mL) from Baseline to Week 12(Baseline and Week 12)
- Change in Mean 24-h Glucose (mg/dL) from Baseline to Week 12(Baseline and Week 12)
- Change in Glucose Coefficient of Variation (CV, %) from Baseline to Week 12(Baseline and Week 12)
- Change in Fasting Serum Triglycerides (mmol/L) from Baseline to Week 12(Baseline and Week 12)
- Change in Triglyceride Incremental AUC (mmol·min/L) from Baseline to Week 12(Baseline and Week 12)
- Change in Fasting Serum Total Cholesterol (mmol/L) from Baseline to Week 12(Baseline and Week 12)
- Change in Total Cholesterol Incremental AUC (mmol·min/L) from Baseline at 12 Weeks(Baseline and Week 12)
- Change in Fasting Serum High-Density Lipoprotein Cholesterol (HDL-C, mmol/L) from Baseline to Week 12(Baseline and Week 12)
- Change in HDL-c Incremental AUC (mmol·min/L) from Baseline to 12 Weeks(Baseline and Week 12)
- Change in Fasting Serum Low-Density Lipoprotein Cholesterol (LDL-C, mmol/L) from Baseline to Week 12(Baseline and Week 12)
- Change in LDL-c Incremental AUC (mmol·min/L) from Baseline to 12 Weeks(Baseline and Week 12)
- Change in GLP-1 Incremental AUC (pg·min/mL) from Baseline to Week 12(Baseline and Week 12)
- Change in GIP Incremental AUC (pg·min/mL) from Baseline to Week 12(Baseline and Week 12)
- Change in Ghrelin Incremental AUC (pg·min/mL) from Baseline to Week 12(Baseline and Week 12)
- Change in Shannon Diversity Index From Baseline to Week 12(Baseline and Week 12)
- Change in Relative Abundance of Akkermansia muciniphila (%) From Baseline to Week 12(Baseline and Week 12)
- Single nucleotide polymorphism (SNPs)(Baseline)
- Change in body weight from Week 12 to 6 months post-intervention(Post-intervention 6 months)
- Change in Facial Skin Phenotype from Baseline to Week 12(Baseline and Week 12)
研究者
Xu Lin
Principal Investigator
Chinese Academy of Sciences