Mapping Metabolic Organ Plasticity in Energy Adaptation

NCT07415213 | Active Not Recruiting

• 1 other identifier: 0003858-5
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

Brief Summary (Plain Language) Many people who lose weight experience a slowdown in their metabolism that is greater than expected. This response, called metabolic adaptation, makes it harder to continue losing weight or to keep weight off over time. The biological reasons for this slowdown are not fully understood. Some organs in the body, especially the liver and kidneys, use a large amount of energy even when the body is at rest. Although these organs make up only a small portion of body weight, they account for a large share of daily energy use. Changes in the size or function of these organs may play an important role in metabolic adaptation, but this has not been well studied in humans. The purpose of this study is to understand how different lifestyle approaches affect metabolic adaptation and the size of key metabolic organs. Specifically, the study compares three common strategies:

• resistance training without calorie restriction,
• a calorie-restricted diet, and
• time-restricted eating (eating all daily food within a limited time window). Adults with overweight will take part in one of these approaches for 10 weeks. Before and after the study period, participants will undergo advanced measurements, including magnetic resonance imaging (MRI) scans to measure liver and kidney size, tests to measure resting metabolism, and assessments of body composition. Some participants will also undergo additional testing to measure daily energy use. By understanding how different lifestyle strategies influence metabolism and organ size, this study aims to improve knowledge about why weight loss is difficult to maintain and to support the development of more personalized approaches to long-term weight management.

Conditions

Overweight , Obesity; Energy Metabolism

Keywords

Metabolic adaptation; Energy expenditure; Metabolic organs; lifestyle modalities; weight loss

Outcome Measures

Primary Outcomes (1)

• Change in Metabolic Adaptation

  Change in metabolic adaptation, defined as the difference between predicted resting metabolic rate and measured resting metabolic rate. Measurement: Resting metabolic rate measured by indirect calorimetry and predicted from body composition-based equations.

  Baseline to 10 weeks

Secondary Outcomes (4)

• Change in Resting Metabolic Rate (RMR)

  Baseline to 10 weeks

• Change in Liver Volume

  Baseline to 10 weeks

• Change in Kidney Volume

  Baseline to 10 weeks

• Association Between Organ Volume Changes and Metabolic Adaptation

  Baseline to 10 weeks

Other Outcomes (2)

• Change in Total Daily Energy Expenditure

  Baseline to 10 weeks

• Change in Body Composition

  Baseline to 10 weeks

Study Arms (3)

Calorie Restriction

EXPERIMENTAL

energy deficit of 500 Kcal/day

Behavioral: Calorie Restriction (CR)

Time Restricted Eating

EXPERIMENTAL

fasting period (8 h eating window with 16 h of fasting).

Behavioral: Resistance Training (RT)

Resistance Training

EXPERIMENTAL

Participants will train for 60 minutes, 3 times a week, using a full-body workout with nine exercises for a major muscle group.

Behavioral: Time Restricted Eating (TRE)

Interventions

Calorie Restriction (CR) BEHAVIORAL

Participants in the CR group will be asked to stay on an energy deficit of 500 Kcal/day, based on their RMR measurement. This intervention is designed to optimize the likelihood that a substantial degree of CR is achieved through a variety of nutritional and behavioural strategies. The CR intervention will be conceptualized as an intensive behavioural approach coupled with dietary modifications and daily self-monitoring of calories, designed to promote adherence to long-term CR. Each participant will be provided with an individualized CR prescription for \~25% CR from baseline ad libitum energy intake as determined by intake as determined by their personalized RMR.

Calorie Restriction

Time Restricted Eating (TRE) BEHAVIORAL

Participants in the TRE groups will be instructed at weekly personal meetings to consume all meals between 10am to 6pm, and to avoid consumption of food or caloric drinks during the fasting period (8 h eating window with 16 h of fasting).

Resistance Training

Resistance Training (RT) BEHAVIORAL

The participants who are assigned to the RT groups will perform supervised and monitored RT three times a week for a duration of 10 weeks. During the first two weeks of training, participants will be familiarized with RT exercises to ensure adoption, adherence, and correction of their technique. Additionally, intensity will increase from 40-60% 1-repetition maximum (1RM). Guided training sessions will start with the evaluation of 10 RM. Participants will train for 60 minutes, 3 times a week, using a full-body workout with nine exercises for a major muscle group. The exercise sessions will last \~60 minutes and will include a five-minute warmup, followed by 50 minutes of resistance exercises, including nine upper- and lower-body exercises using weight-lifting machines. In every training session, subjects will complete between 8-12 repetitions. If subjects successfully finish three sets of 12 reps, extra weight will be added to maintain an increased intensity. The r

Time Restricted Eating

Eligibility Criteria

• Age: 25 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Sedentary men and women aged 25-60 years
• Body mass index (BMI) of 25-35 kg/m²

You may not qualify if:

• Participation in another exercise or weight loss program in the last 6 months
• Non-stable weight (\>±5%) over the past 6 months
• Smoking within the past 6 months
• Post-menopause
• Breastfeeding
• Pregnancy or having been pregnant within the past 6 months
• Contraindication for MRI scans (e.g., tattoos, intrauterine devices, permanent makeup, etc.)
• Severe cardiopulmonary disease (e.g., recent myocardial infarction or unstable angina)
• Musculoskeletal or neuromuscular impairments that preclude exercise training
• Cognitive impairments
• Other health issues, including cancer, diabetes, thyroid disease, hypertension, or chronic renal failure
• Use of drugs that affect body metabolism
• Secondary liver disease (viral, autoimmune, alcoholic, or hepatotoxic)
• Alcohol consumption above 20 g/day for women or 30 g/day for men

Sponsors & Collaborators

• Tel Aviv University: lead

Study Sites (1)

Sylvan Adams Sport Institute

Tel Aviv, 69978, Israel

Location

MeSH Terms

Conditions

Overweight; Obesity; Weight Loss

Interventions

Caloric Restriction; Resistance Training

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator - Prof.

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: February 17, 2026
• Study Start: February 3, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)