Establishment of a Specific Metabolic Phenotyping for the Personalization of Obesity Therapy in Morbidly Obese Individuals
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Change in Resting Metabolic Rate (RMR) From Baseline to 24 Hours After Fasting
研究概览
简要总结
This study aims to develop a simple, clinically applicable method for metabolic phenotyping to personalize obesity therapy in morbidly obese individuals. The underlying concept is that the way a person's resting metabolic rate (RMR) responds to a 24-hour fast can help distinguish between two metabolic phenotypes. Individuals with a "thrifty" metabolism show a significant drop in RMR during fasting, which may make them less responsive to conventional weight loss interventions. In contrast, those with a "spendthrift" metabolism exhibit little to no drop-or even a slight increase-in RMR, suggesting they may lose weight more readily.
The trial is designed as a prospective, single-center, longitudinal cohort study involving 20 morbidly obese patients (BMI >40 kg/m²) who are already participating in a multimodal obesity therapy program. The study is divided into three phases. In the baseline phase, participants undergo comprehensive screening, which includes physical examinations, blood tests, and body composition assessments. RMR is measured using indirect calorimetry both before and after a 24-hour fasting period, and a device (Lumen™) is used to assess whether the body is primarily burning carbohydrates or fats.
After the fasting measurements, participants perform a low-protein meal test by consuming a specially calibrated chocolate beverage. Their RMR is then monitored at several time points to determine the energy required for digestion. Following this, the study moves into the very-low-calorie diet (VLCD) phase, where participants consume approximately 800 kcal per day using formula meals tailored to meet their nutritional needs despite the calorie restriction. During this 12-week phase, changes in body weight, composition, and metabolic parameters are closely monitored.
The final phase of the study is a 12-week weight maintenance period, during which the focus is on sustaining the achieved weight loss. In addition to RMR and dietary assessments, advanced techniques such as metabolomics are employed. Blood, urine, and saliva samples are collected to analyze metabolic profiles and identify potential hormonal biomarkers-such as leptin, FGF21, and adrenaline-that could further differentiate the "thrifty" and "spendthrift" phenotypes. Body composition is also assessed using methods like bioimpedance analysis (BIA), quantitative magnetic resonance imaging (qMR), and air displacement plethysmography (BodPod).
By correlating the changes in RMR with metabolic and hormonal markers, the study tests the hypothesis that individuals with a marked RMR decrease during fasting (the "thrifty" phenotype) may experience less weight loss during a hypocaloric diet compared to those with minimal RMR change (the "spendthrift" phenotype). If validated, this approach could allow clinicians to predict weight loss outcomes more accurately and tailor obesity treatments to the individual's unique metabolic profile.
详细描述
This study is a prospective, single-center, longitudinal cohort trial designed to unravel the metabolic heterogeneity among morbidly obese individuals and to develop a clinically feasible method for metabolic phenotyping. The aim is to identify distinct metabolic responses to a controlled fasting period that may predict weight loss outcomes and guide personalized obesity therapy.
Potential participants are morbidly obese patients (BMI >40 kg/m²) already enrolled in a multimodal obesity therapy program at the University Hospital Schleswig-Holstein, Campus Kiel. The screening process includes a thorough medical history, physical examination, and laboratory testing to exclude confounding conditions that might affect energy expenditure or the interpretation of metabolic measurements.
In the baseline phase, enrolled subjects undergo extensive assessments to characterize their metabolic status. Body composition is evaluated using several complementary techniques: bioimpedance analysis (BIA), quantitative magnetic resonance imaging (qMR), and air displacement plethysmography (BodPod). These methods provide detailed insights into fat mass, lean mass, and overall body composition. Resting metabolic rate (RMR) is measured using indirect calorimetry, with subjects placed under a canopy (haubenkalorimeter) that records oxygen consumption and carbon dioxide production to yield precise energy expenditure data.
A critical component of the study is the evaluation of RMR before and after an extended fasting period. Initially, RMR is measured following a 12-hour overnight fast. Participants then complete a 24-hour fasting period, during which continuous monitoring-via devices such as a continuous glucose monitor-ensures compliance with the fasting protocol. A second RMR measurement is taken after the fasting period, and the percentage change in RMR is calculated. Based on previous research, a significant RMR reduction (≥5.7%) classifies a subject as having a "thrifty" metabolic phenotype, while a minimal reduction or slight increase (≥+3.8%) indicates a "spendthrift" phenotype. Subjects with intermediate changes are not categorized for the primary analysis.
Following the fasting assessments, participants undergo a low-protein meal test. They consume a standardized chocolate beverage calibrated to provide 50% of their baseline RMR in caloric content. Postprandial RMR is then measured at several intervals over a three-hour period to assess the thermic effect of food and the energy cost associated with digestion. This test helps to elucidate differences in nutrient oxidation and metabolic flexibility between the two phenotypes.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Morbid obesity (BMI > 40 kg/m²)
- •Currently undergoing a multimodal obesity therapy program at the Department of Internal Medicine I at the University Hospital Schleswig-Holstein (UKSH), Campus Kiel
排除标准
- •Type 1 or Type 2 diabetes mellitus, or fasting blood glucose >125 mg/dL, or HbA1c >6.5%
- •Conditions affecting appetite or energy expenditure (e.g., Cushing's syndrome, uncontrolled hyper-/hypothyroidism, diabetes mellitus)
- •Gastrointestinal diseases that may impair nutrient absorption (e.g., inflammatory bowel disease, malabsorption syndromes, peptic ulcers)
- •Psychiatric disorders that influence eating behavior (e.g., active depression, anorexia nervosa, bulimia nervosa, borderline personality disorder)
- •Acute, unstable cardiovascular disease requiring hospitalization within the last 6 months (e.g., stent implantation)
- •Cancer requiring treatment within the past 5 years
- •Chronic kidney disease at Stage IV or worse according to NKF criteria
- •Active infectious disease (e.g., HIV, hepatitis)
- •Active nicotine use
- •Drug use (e.g., amphetamines, cocaine, heroin, marijuana)
- •Regular intense physical activity (≥1 hour of sport per day)
- •Non-MRI-compatible metallic implants (e.g., joint replacements, metal plates)
- •Pregnancy or breastfeeding
- •Use of weight-loss medications
- •Clinically relevant claustrophobia
- •Any other condition not specified above that, in the judgment of the investigator, could interfere with study participation or compromise patient safety
研究组 & 干预措施
No extreme phenotype
Individuals with fasting-induced RMR changes greater than -5.7% and lower than +3.8%
Extreme Thrifty
Individuals with a fasting-induced decrease of RMR < -5.7%
Extreme Spendthrift
Individuals with a fasting-induced increase of RMR > +3.8%
结局指标
主要结局
Change in Resting Metabolic Rate (RMR) From Baseline to 24 Hours After Fasting
时间窗: Baseline to Week 12
RMR (measured in kcal/day) is assessed via indirect calorimetry at baseline (after an overnight fast) and again following a 24-hour fasting period. The primary metric is the absolute change in RMR (kcal/day) or percentage change from baseline. Participants who experience a significant RMR decrease ("thrifty" phenotype) are hypothesized to lose less weight during a subsequent hypocaloric diet than those with a minimal or increased RMR ("spendthrift" phenotype).
次要结局
- Change in Plasma FGF21 From Baseline to 24 Hours After Fasting(Baseline, after 24-hour fast, and throughout the 6-month study period (up to Week 26))
- Meal-Induced Thermogenesis as a Predictor of Weight and Fat Mass Loss(Day 1 (immediately following 24-hour fast) for the low-protein meal test, with follow-up assessments at Week 12 (end of VLCD) and Week 26 (end of weight maintenance).)
- Metabolic Flexibility (Respiratory Quotient Changes)(Baseline (Day 0), after 24-hour fast (Day 1), and during the low-protein meal test (Day 1))
- Subjective Hunger After 24-Hour Fast(Baseline (Day 0) and after 24-hour fast (Day 1))
- Changes in Fat Mass During and After a Hypocaloric Diet(Baseline, Week 12 (end of VLCD), and Week 26 (end of maintenance phase))
- Gut Microbiome Differences(Baseline, Week 12, and Week 26)
- Thermogenic and Appetite-Regulating Hormone Composite Index(Baseline, after 24-hour fast (Day 1), Week 12, and Week 26)
- Long-Term Change in Metabolic Phenotype(Baseline, Week 12, and Week 26)
- Association of RMR Changes With Meal-Induced Thermogenesis(Baseline (Day 0) and during low-protein meal test (Day 1))
- Association Between CO₂ Production and Energy Expenditure(Baseline (Day 0), after 24-hour fast (Day 1), and throughout the 6-month study period)
- Correlation Between Resting Metabolic Rate and Respiratory Quotient(Baseline (Day 0), after 24-hour fast (Day 1), and during subsequent diet phases (up to Week 26))
- Correlation Between Diet-Induced Thermogenesis (DIT) and Postprandial FGF21 Levels(During the low-protein meal test (Day 1) and optionally at subsequent time points (Week 12, Week 26))
研究者
Tim Hollstein
PD Dr. med.
University Hospital Schleswig-Holstein