Association Between Food Intake-Related Brain Functional Patterns and Metabolic Profiles in Patients With Obesity: A Randomized Crossover Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Acute Brain Functional Response to Macronutrient Challenges
研究概览
简要总结
This study is a prospective, single-center, randomized, controlled, crossover intervention trial. A total of 60 participants, including 30 patients with obesity and 30 healthy controls, will be enrolled. Each participant will receive an isocaloric liquid meal challenge (glucose, fat, or protein) on three separate experimental days, with a washout period of at least 7 days between visits to eliminate carryover effects from the previous intervention. The primary objective is to investigate the association between brain functional patterns and plasma metabolic profiles following the ingestion of different macronutrients in patients with obesity, aiming to uncover potential neuro-metabolic imbalance features.
详细描述
This study is a prospective, single-center, randomized, controlled, crossover intervention trial enrolling 60 participants, including 30 obese patients and 30 healthy control volunteers. Each participant will be randomly assigned to one of the six possible sequences of three macronutrient interventions (A: glucose, B: fat, C: protein)-namely ABC, ACB, BAC, BCA, CAB, or CBA-to ensure balanced allocation across intervention orders. Each participant will undergo one nutrient challenge on each of three separate experimental days, with at least a 7-day washout period between visits to minimize carryover effects from prior interventions. During the washout periods, participants are required to maintain stable habitual dietary patterns and avoid extreme diets, high-intensity exercise, irregular sleep schedules, and intake of additional nutritional supplements; adherence will be monitored via brief diet and activity logs.
The intervention consists of isocaloric (200 kcal) and isovolumetric (300 mL) liquid meals, specifically formulated as follows: Glucose arm: 50 g glucose powder dissolved in water to a final volume of 300 mL; Fat arm: 100 mL intralipid emulsion diluted with water to a final volume of 300 mL; Protein arm: 54 g whey protein powder dissolved in water to a final volume of 300 mL. On each experimental day, participants must arrive in a fasting state. Prior to nutrient administration, they will complete clinical laboratory tests, body composition assessment, hepatic fat quantification, and eating behavior questionnaires. During and after the intervention, participants will provide dynamic postprandial satiety ratings, multi-timepoint blood and stool samples (for untargeted metabolomic analysis), and undergo functional magnetic resonance imaging (fMRI) within a predefined postprandial time window. Finally, neuroimaging metrics, peripheral metabolomic profiles, and subjective satiety scores will be integrated through multidimensional correlation analyses to explore the neuro-metabolic coupling responses to different macronutrient challenges in obesity, thereby providing theoretical insights and potential targets for precision nutrition interventions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Obese participants:
- •BMI ≥ 28 kg/m²;
- •Age 18-40 years;
- •Any gender;
- •Right-handed.
- •Healthy control participants:
- •BMI 18.5-23.9 kg/m²;
- •Age 18-40 years;
- •Any gender;
- •Right-handed.
排除标准
- •Diabetes mellitus;
- •Contraindications or allergies to any ingredient in the standardized meal or macronutrient challenges used in this study;
- •Central nervous system disorders (e.g., traumatic brain injury, acute cerebral infarction, epilepsy) or psychiatric disorders (e.g., depression, schizophrenia); use of medications acting on the central nervous system within the past 3 months or long-term use;
- •Severe impairment of liver, kidney, heart, or gastrointestinal function, including alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels >2 times the upper limit of normal; estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m² calculated by the CKD-EPI equation; history of unstable angina or myocardial infarction within the past 3 months, or heart failure classified as New York Heart Association (NYHA) class II or higher; history of gastrointestinal stoma, bowel resection, intestinal obstruction, or peptic ulcer disease;
- •Contraindications to MRI, such as implanted metallic devices or claustrophobia;
- •Pregnancy or lactation;
- •Participation in another clinical trial currently or within the past 3 months; use of nutritional supplements within the past 3 months or long-term use;
- •History of prior metabolic/bariatric surgery;
- •Use of antibiotics or probiotics within the past 1 month;
- •Use of medications affecting metabolism or causing weight loss within the past 1 month; body weight fluctuation exceeding 3 kg during the month prior to screening;
- •Unusual dietary habits; daily alcohol intake >40 grams, smoking >10 cigarettes per day, or coffee consumption ≥2 cups per day.
研究组 & 干预措施
Glucose Challenge
Participants receive a single 200 kcal liquid meal consisting of 50 g glucose powder dissolved in water to a final volume of 300 mL, administered 6 hours after consuming a standardized pre-load meal.
干预措施: Glucose Liquid Meal (Dietary Supplement)
Fat Challenge
Participants receive a single 200 kcal liquid meal consisting of 100 mL intralipid emulsion diluted with water to a final volume of 300 mL, administered 6 hours after consuming a standardized pre-load meal.
干预措施: Fat Liquid Meal (Dietary Supplement)
Protein Challenge
Participants receive a single 200 kcal liquid meal consisting of 54 g whey protein isolate powder dissolved in water to a final volume of 300 mL, administered 6 hours after consuming a standardized pre-load meal.
干预措施: Protein Liquid Meal (Dietary Supplement)
结局指标
主要结局
Acute Brain Functional Response to Macronutrient Challenges
时间窗: Baseline (pre-challenge) and within 0-20 minutes post-challenge on each experimental day
Changes in whole-brain functional activation patterns assessed by blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), comparing pre-challenge baseline with post-challenge scans acquired within 20 minutes after ingestion of glucose, fat, or protein.
Dynamic Plasma Metabolomic Response to Macronutrient Challenges
时间窗: Baseline (pre-challenge), 30 minutes post-challenge, and 120 minutes post-challenge on each experimental day.
Temporal changes in plasma metabolic profiles characterized by untargeted metabolomic profiling, evaluating the evolution of metabolite concentrations across three time points: before intervention, 30 minutes post-intervention, and 120 minutes post-intervention, following single-dose challenges with glucose, fat, or protein.
次要结局
- Temporal Changes in Subjective Satiety and Hunger Ratings(Pre-challenge, 0 minutes, 30 minutes, and 120 minutes post-challenge on each experimental day.)
- Inter-group Differences in Brain Functional and Metabolic Responses Between Obese and Healthy Participants(Baseline, within 0-20 minutes (fMRI), and 30/120 minutes (metabolomics) post-challenge on each experimental day)
- Changes in Gut Microbiota Composition and Alpha/Beta Diversity Following Macronutrient Challenges(Approximately 24 hours before intervention and approximately 24 hours after intervention on each experimental day)
研究者
Yan Bi
Chief Physician
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School