Metabolic Flexibility and Metabolic Heath in Human Obesity (PROB)

February 24, 2026 updated by: Jose Galgani

Metabolic Flexibility, Eating Behavior and Adipose Tissue Expandability: Role of This Triad in the Propensity to Human Obesity

This interventional study explores the relationship between improvements in metabolic health following weight loss and changes in whole-body fat mass and its distribution. The study focuses on adult men and women with excess body weight undergoing dietary energy restriction over 12 weeks. The primary research question is: Does a greater reduction in fat mass for a given weight loss correlate with more significant improvements in metabolic health?

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Obesity is a well-established risk factor for disruptions in metabolic health, which often precede cardiovascular disease and type-2 diabetes. While the precise pathophysiological mechanisms linking obesity to these conditions remain unclear, it is widely acknowledged that an increase in fat mass plays a central role, including the expansion of adipose tissue and the accumulation of lipids in non-adipose tissues. As a result, a primary approach to improving metabolic health is to reduce fat mass through negative energy balance. However, lifestyle changes or pharmacological interventions aimed at inducing a negative energy balance do not exclusively target fat mass and often result in the loss of fat-free mass to varying degrees. Given that higher fat mass, rather than fat-free mass, is more strongly associated with impaired metabolic health, strategies that maximize fat mass loss while preserving fat-free mass may offer more significant benefits for metabolic health. Surprisingly, there is a lack of evidence to support this hypothesis. To address this gap, it will be evaluated the relationship between changes in metabolic health and body composition, independent of overall weight loss, in individuals with overweight or obesity undergoing dietary energy restriction. It is hypothesized that greater fat mass reduction will be linked to more substantial improvements in metabolic health for a given weight loss.

Study Type

Interventional

Enrollment (Actual)

74

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Chile
      • Santiago, Chile
        • Avda. Libertador Bernardo O´Higgins 340. Santiago. Chile.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion criteria

  • males or females
  • 30-55 y old
  • physically inactive (<600 MET´min/wk of self-reported moderate-vigorous physical activity
  • stable body weight for at least the past 6 months (±2 kg)
  • healthy according to medical history and routine hematology and biochemistry.

Exclusion criteria

  • Individuals with physiological (pregnancy, lactation) or pathological (under drug therapy for and/or having cardiovascular, liver, kidney, thyroid diseases)
  • conditions affecting energy metabolism or eating behavior
  • Subjects having low-fat (<20% energy) or low-carbohydrate (<45% energy) diets
  • Smokers and alcohol abusers

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Weight Loss Intervention
Individuals with overweight or obesity will undergo dietary energy restriction aimed to induce 8 to 12% weight loss after 12 weeks. For 3 to 5 weeks, body weight will be maintained.
Other: Body Weight Loss
Individuals will be prescribed a hypocaloric diet (1300 kcal/d). Individuals will receive a booklet detailing the type of meals and foods to be consumed in each mealtime. A dietitian will explain how to enhance dietary compliance. Every two weeks, body weight, vital signs, and adverse events will be monitored. In addition, food recalls will be conducted in order to optimize dietary energy restriction compliance. During weight maintenance, energy intake will be adjusted to energy requirements to maintain weight stability (±2.5 kg) for at least 3 weeks. During weight loss and maintenance, participants will be instructed to maintain their customary physical activity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fasting serum triglyceride concentration
Time Frame: From enrollment to the end of weight maintenance period at 15-20 weeks
In overnight fasted individuals, a blood sample will be drawn. Serum will be isolated and stored at -80C until assessment.
From enrollment to the end of weight maintenance period at 15-20 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HOMA-IR
Time Frame: From enrollment to the end of weight maintenance period at 15-20 weeks.
In overnight fasted individuals, a blood sample will be drawn for glucose and insulin assessment. HOMA-IR will be calculated using this formula: (glucose, mM * insulin, uU/mL)/22.5. Serum/Plasma will be isolated and stored at -80C until assessment.
From enrollment to the end of weight maintenance period at 15-20 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jose Galgani

Collaborators

Agencia Nacional de Investigación y Desarrollo

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 23, 2022

Primary Completion (Actual)

January 6, 2025

Study Completion (Actual)

January 6, 2025

Study Registration Dates

First Submitted

July 25, 2025

First Submitted That Met QC Criteria

January 12, 2026

First Posted (Actual)

January 21, 2026

Study Record Updates

Last Update Posted (Actual)

February 27, 2026

Last Update Submitted That Met QC Criteria

February 24, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 200602001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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