Clinical trial NCT06989177: Probiotic Intervention on Body Weight
Official title: An Interventional Study Investigating the Effects of Probiotics on Body Weight and Metabolic Homeostasis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Obesity
Homeostasis
Weight Loss
Probiotic Intervention
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 controlled trial with 120 overweight or obese (body-mass index, BMI, ≥ 24 kg/m²) participants and 20 normal-weight participants. Twelve weeks of energy-restricted nutritional and lifestyle intervention with placebo, Lactobacillus paracasei LC-19 (LC-19), or semaglutide (a glucagon-like peptide-1 receptor agonist, GLP-1RA) will be randomly conducted in the overweight or obese participants. The primary goal is to clarify the roles of LC-19 and semaglutide in weight reduction and in improving energy, glucose, and lipid metabolism, while also comparing side effects, adverse events, and long-term outcomes such as weight regain between these two interventions. In addition, the study will explore key factors affecting intervention response to provide evidence for optimizing individualized intervention strategies.

Detailed description: The primary goal is to clarify the roles of LC-19 and semaglutide in weight reduction and in improving energy, glucose, and lipid metabolism, while also comparing side effects, adverse events, and long-term outcomes such as weight regain between these two interventions. In addition, the study will explore key factors affecting intervention response to provide evidence for optimizing individualized intervention strategies.

In this study, 120 overweight or obese participants (BMI ≥ 24 kg/m²) will be recruited and be randomly assigned to one of the three groups: an energy-restricted nutritional and lifestyle intervention + placebo group (control group), an energy-restricted nutritional and lifestyle intervention plus LC-19 group (probiotic group), or an energy-restricted nutritional and lifestyle intervention plus semaglutide injection group (GLP-1RA group), with a 12-week intervention. In addition, 20 normal-weight participants will be recruited and receive 12-week weight maintenance nutritional and lifestyle interventions. Before and after the 12-week interventions, metabolic homeostasis will be used to characterize metabolic health and to be determined using comprehensive measurements of dynamic changes in postprandial metabolic responses (including energy metabolism, multiple clinical biomarkers, metabolomic signatures, gut microbiota, genetic signatures etc.) after the standardized mixed-meal tolerance test (MMTT; 126.5 g glucose, 30.67 g fat and 34.5 g protein) in whole-room indirect calorimeter under resting conditions. In addition, data from dietary intake, anthropometric measurements, body composition, behavior questionnaires, 14-day continuous glucose monitoring, and 14-day accelerometer-based physical activity and sleep monitoring will also be collected to characterize metabolic homeostasis. During the interventions, participants will receive dietary advice, behavior guidance and nutritional and lifestyle education by dietitian and physicians. App-connected wearable devices will be utilized to monitor their dietary intakes and an app-connected scale will be used to monitor their weight changes during interventions. Additionally, at 6 months post-intervention, a follow-up assessment will be conducted, including questionnaires (consistent with the baseline visit), anthropometry (e.g., height, weight, waist and hip circumference, blood pressure, pulse), clinical laboratory tests (e.g., blood glucose, blood lipids, liver and kidney function), and stool sample collection. The study protocol has been approved by the Ethics Committee of Tongde Hospital of Zhejiang Province.

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/min) 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/min) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Carbohydrate Oxidation Rate (g/min) 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 Mass (kg) 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 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/min) 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 (Week 0) 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 Insulin (µIU/mL) from Baseline to Week 12
timeFrame: Baseline and Week 12
measure: Change in Insulin Incremental AUC (µIU·min/mL) from Baseline to Week 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 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 Serum Fasting 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 to Week 12
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 Week 12
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 Week 12
timeFrame: Baseline and Week 12
measure: Change in GLP-1 Incremental AUC (pg·min/mL) from Baseline to Week 12
timeFrame: Baseline (Week 0) 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 Polymorphisms (SNPs)
timeFrame: Baseline
measure: Change in body weight from Week 12 to 6 months post-intervention
timeFrame: Post-intervention 6 months
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: