Clinical trial NCT06860776: How Metabolism Affects Weight Loss and Gain
Official title: Pilot Study on the Analysis of the Metabolic Phenotype in Individuals With Difficulties in Losing and Gaining Weight
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Obesity and Overweight
Keywords: obesity
metabolic phenotype
thrifty
spendthrift
diet-induced thermogenesis
fasting
indirect calorimetry
Lead sponsor: University Hospital Schleswig-Holstein
Sponsor class: OTHER
First posted: 2025-03-06
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will be recruited from the general adult population, focusing on two specific groups:

1. Lean individuals (BMI 18.5-22.0 kg/m²) who struggle to gain weight
2. Individuals with obesity (BMI \>30 kg/m²) who struggle to lose weight

All participants must be generally healthy, between 18 and 70 years old, and report a stable body weight (less than 5% fluctuation) in the last six months. Recruitment will occur via community outreach, advertisements, and existing volunteer registries. Potential participants with conditions or circumstances that could affect appetite, energy expenditure, or study compliance will be excluded.

Brief summary: This study examines why some individuals with obesity have difficulty losing weight, whereas some lean individuals struggle to gain weight. The investigators will measure how the human body uses energy during a fasting period and after consumption of a specially designed, low-protein meal. By comparing these responses, the investigators aim to identify different "metabolic phenotypes" that affect weight control. Findings from this research may lead to more personalized treatments for managing weight. Participation in this study involves simple tests and basic body measurements.

Detailed description: This study aims to better understand why certain individuals find it difficult to lose weight while others struggle to gain weight. Investigators believe that differences in how the human body uses energy-referred to as the metabolic phenotype-may play a key role.

Two groups of participants will be compared: one group includes lean individuals who have difficulty gaining weight, and the other group consists of individuals with obesity who have difficulty losing weight. Participants will undergo a series of tests designed to measure how the human body burns calories under different conditions.

The study involves two main components:

1. 24-Hour Fasting Period: Participants will abstain from eating for 24 hours to observe how the body adapts by either conserving or maintaining energy expenditure.
2. Meal Test: Following the fasting period, participants will consume a specially designed, low-protein meal that simulates overeating. The investigators will measure how much additional energy is burned during digestion, a process known as diet-induced thermogenesis.

A technique called indirect calorimetry will record oxygen consumption and carbon dioxide production. These measurements help calculate resting energy expenditure (REE), which refers to the calories the body burns while at rest, and any changes that occur after fasting and eating.

The goal is to identify distinct metabolic patterns. Some individuals may have a "thrifty" metabolism that conserves energy, making weight loss more challenging, whereas others may have a "spendthrift" metabolism that expends more energy, potentially explaining difficulty in gaining weight. Understanding these differences could lead to more personalized and effective weight management strategies.

This study is conducted under strict safety and ethical standards to ensure minimal risk to participants. By examining the relationship between metabolism and weight control, the findings may pave the way for improved treatments for obesity and related weight issues.

Eligibility criteria: Inclusion Criteria:

* Group 1 (Lean): BMI 18.5-22.0 kg/m², reporting difficulty gaining weight
* Group 2 (Obese): BMI \>30 kg/m², reporting difficulty losing weight
* Healthy status as determined by medical history, physical examination, and laboratory tests
* Stable weight (less than 5% fluctuation) over the past 6 months

Exclusion Criteria:

* Prediabetes (HbA1c \>5.6% or fasting blood glucose \>100 mg/dL) or diabetes mellitus
* Conditions affecting appetite or energy expenditure (e.g., Cushing's syndrome, uncontrolled hyper-/hypothyroidism)
* Gastrointestinal disorders that impact nutrient absorption (e.g., inflammatory bowel disease, malabsorption syndromes, ulcers)
* Psychiatric conditions influencing 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 placement)
* Cancer that required treatment in the past 5 years
* Chronic kidney disease (Stage IV or higher, per NKF criteria)
* Active infectious disease (e.g., HIV, hepatitis)
* Current nicotine use or nicotine use within the last month prior to screening
* Illicit drug use (e.g., amphetamines, cocaine, heroin, marijuana)
* Regular high-intensity physical activity (≥1 hour/day)
* Non-MRI-compatible metallic implants (e.g., artificial joints, metal plates)
* Pregnancy or breastfeeding
* Use of weight-loss medications
* Clinically significant claustrophobia
* Any other condition not mentioned above that, in the opinion of the investigator, could interfere with study participation or compromise patient safety

Primary outcomes:
measure: Identification of Metabolic Phenotypes in Lean vs. Obese Individuals
timeFrame: Measured at baseline (Day 1) and after 24-hour fasting (Day 2)
Secondary outcomes:
measure: Correlation Between Fasting-Induced Energy Expenditure Changes and Diet-Induced Thermogenesis
timeFrame: Baseline (Day 1), post-fasting (Day 2), and after the meal test (Day 2)
measure: Assessment of Metabolic Flexibility via Respiratory Quotient
timeFrame: Baseline (Day 1), post-fasting (Day 2), and after the meal test (Day 2)
measure: Correlation Between Weight Gain at 12-Month Follow-Up and Initial Metabolic Phenotype
timeFrame: 12-month follow-up
measure: Correlation Between Weight Gain at 12-Month Follow-Up and Diet-Induced Thermogenesis
timeFrame: 12-month follow-up
measure: Correlation Between Meal Test Diet-Induced Thermogenesis and Fibroblast Growth Factor 21 (FGF-21) Secretion
timeFrame: After the meal test (Day 2)
measure: Correlation Between Gut Hormones and Changes in Energy Expenditure
timeFrame: Baseline (Day 1), after 24-hour fast (Day 2), and after the meal test (Day 2)
Other outcomes:
Locations:
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein
state: Schleswig-Holstein
Study officials:
References: