Clinical trial NCT06989203: Protein Supplementation Intervention on Body Weight
Official title: An Intervention Study Investigating Effect of Dietary Protein Supplementation on Body Weight and Metabolic Homeostasis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Obesity
Weight Loss
Protein Supplementation
Lead sponsor: Chinese Academy of Sciences
Sponsor class: OTHER_GOV
First posted: 2025-05-25
Enrollment: 140
Sex: ALL
Minimum age (years): 20
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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:

1. CRD: calorie restricted balanced diet;
2. CRD + GLP-1RA: CRD plus semaglutide;
3. 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.

Six months after the intervention, participants undergo follow up assessments (identical questionnaires, physical examination, fasting laboratory tests for glucose, insulin, HbA1c, lipids, and liver and renal function indices) and provide a stool sample.

To provide a healthy reference, Investigators will additionally recruit 20 normal weight adults who will receive weight maintenance dietary counseling for 3 months and undergo pre and post intervention MMTTs in the metabolic chamber. These data will help determine whether the metabolic homeostasis of overweight/obese participants after the three interventions approaches that of healthy individuals and will aid in identifying determinants of inter individual variability.

The study protocol has been approved by the Ethics Committee of Zhejiang Provincial Tongde Hospital.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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):
  1. Waist circumference ≥ 90 cm for men or ≥ 85 cm for women.
  2. Fasting glucose ≥ 6.1 mmol/L or 2-hour postprandial glucose ≥ 7.8 mmol/L, or a confirmed diagnosis of diabetes.
  3. Systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85 mmHg, or currently under antihypertensive treatment.
  4. 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):
  1. Fasting plasma glucose \> 11.1 mmol/L or HbA1c \> 9%, or previously diagnosed diabetes, or currently using insulin or any antidiabetic medication.
  2. Blood pressure ≥ 160/100 mmHg, or clinically diagnosed stage 2 or stage 3 (moderate or severe) hypertension, or currently under antihypertensive treatment.
  3. 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.

Primary outcomes:
measure: Change in Body Weight (kg) from Baseline to Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change in Energy Expenditure Rate (kcal/minute) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Respiratory Quotient from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Fat Oxidation Rate (g/minute) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Carbohydrate Oxidation Rate (g/minute) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Waist Circumference (cm) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Hip Circumference (cm) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Fat-free Mass (kg) From Baseline to Week 12
timeFrame: Baseline (Week 0) and Week 12
measure: Change in Fat Mass (kg) From Baseline to Week 12
timeFrame: Baseline (Week 0) and Week 12
measure: Change in Controlled Attenuation Parameter (CAP, dB/m) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Systolic Blood Pressure (mmHg) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Diastolic Blood Pressure (mmHg) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Heart Rate (beats/minute) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Fasting Glucose (mmol/L) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Glucose Incremental AUC (mmol·min/L) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in HbA1c (%) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Fasting Insulin (µIU/mL) from Baseline to Weel 12
timeFrame: Baseline and Week 12
measure: Change in Insulin Incremental AUC (µIU·min/mL) from Baseline to Weel 12
timeFrame: Baseline and Week 12
measure: Change in Fasting C-peptide (ng/mL) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in C-peptide Incremental AUC (ng·min/mL) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Mean 24-h Glucose (mg/dL) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Glucose Coefficient of Variation (CV, %) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Fasting Serum Triglycerides (mmol/L) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Triglyceride Incremental AUC (mmol·min/L) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Fasting Serum Total Cholesterol (mmol/L) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Total Cholesterol Incremental AUC (mmol·min/L) from Baseline at 12 Weeks
timeFrame: Baseline and Week 12
measure: Change in Fasting Serum High-Density Lipoprotein Cholesterol (HDL-C, mmol/L) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in HDL-c Incremental AUC (mmol·min/L) from Baseline to 12 Weeks
timeFrame: Baseline and Week 12
measure: Change in Fasting Serum Low-Density Lipoprotein Cholesterol (LDL-C, mmol/L) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in LDL-c Incremental AUC (mmol·min/L) from Baseline to 12 Weeks
timeFrame: Baseline and Week 12
measure: Change in GLP-1 Incremental AUC (pg·min/mL) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in GIP Incremental AUC (pg·min/mL) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Ghrelin Incremental AUC (pg·min/mL) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Shannon Diversity Index From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Relative Abundance of Akkermansia muciniphila (%) From Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Single nucleotide polymorphism (SNPs)
timeFrame: Baseline
measure: Change in body weight from Week 12 to 6 months post-intervention
timeFrame: Post-intervention 6 months
measure: Change in Facial Skin Phenotype from Baseline to Week 12
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences
state: Zhejiang
Study officials:
affiliation: Institute for Nutritional Sciecnes, CAS; Hangzhou Institute for Advanced Study, UCAS
name: Xu Lin, PhD
role: PRINCIPAL_INVESTIGATOR
References: