Metabolic Phenotyping for Personalized Obesity Therapy

NCT06874270 | Recruiting

• 2 other identifiers: D 496/21508000993
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity and Overweight

Keywords

obesity; metabolic phenotype; thrifty; spendthrift; weight loss; indirect calorimetry; fasting; meal test; VLCD

Outcome Measures

Primary Outcomes (1)

• Change in Resting Metabolic Rate (RMR) From Baseline to 24 Hours After Fasting

  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).

  Baseline to Week 12

Secondary Outcomes (12)

• 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)

Study Arms (3)

Extreme Thrifty

Individuals with a fasting-induced decrease of RMR \< -5.7%

Extreme Spendthrift

Individuals with a fasting-induced increase of RMR \> +3.8%

No extreme phenotype

Individuals with fasting-induced RMR changes greater than -5.7% and lower than +3.8%

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of adult men and women (ages 18 to 70) with a body mass index (BMI) above 40 kg/m² who are receiving care at the Department of Internal Medicine I at the University Hospital Schleswig-Holstein (UKSH), Campus Kiel. All participants are enrolled in a multimodal obesity therapy program that includes nutritional counseling, behavioral interventions, and exercise components. Eligible individuals must meet the specified inclusion criteria and have no conditions that could confound study results or compromise patient safety.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Schleswig-Holstein: lead

Study Sites (1)

University Hospital Schleswig-Holstein

Kiel, Schleswig-Holstein, 24105, Germany

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood, Saliva, Urine

MeSH Terms

Conditions

Obesity; Overweight; Weight Loss; Fasting

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes; Feeding Behavior; Behavior

Central Study Contacts

Tim Hollstein, PD Dr. med.

CONTACT

+4943150022000; tim.hollstein@uksh.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. med.

Study Record Dates

• First Submitted: February 27, 2025
• First Posted: March 13, 2025
• Study Start: September 15, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2027
• Last Updated: March 13, 2025

Record last verified: 2025-03

Locations

DE (1)