New Mechanisms of Obesity

NCT ID: NCT06768827

Last Updated: 2026-01-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-13
• Study Completion Date: 2030-03-31

Brief Summary

Given the pervasiveness of Pediatric Obesity, it is imperative to understand its pathophysiology and develop alternative strategies to reverse this condition. Herein, investigators propose to elucidate the interaction between colonic fermentation and insulin resistance in modulating metabolism in youth with obesity.

Detailed Description

Pediatric obesity is a major health burden affecting millions of children and adolescents as it predisposes to the development of cardio-metabolic diseases early in life, such as insulin resistance, fatty liver disease and type 2 diabetes. Investigators have recently completed a series of studies to understand the relationship between the intestinal microbial activity and human metabolism in youth. It was observed that intestinal fermentation, a process through which fermentable carbohydrates are processed by intestinal bacteria, results in a variety of biological responses aimed at protecting the human body from developing obesity and some of its metabolic complications, such as insulin resistance and ectopic fat accumulation. In particular, investigators observed that intestinal fermentation causes 1- a reduction of plasma free fatty acids (FFA), due to the inhibition of adipose tissue lipolysis (ATL); 2- a marked entero-endocrine response to reduce appetite, characterized by an increase in the production of peptide YY (PYY) and glucagon-like peptide1 (GLP-1) and a reduced production of ghrelin. In addition, investigators observed that some intestinal fermentation responses are impaired in youth with obesity and insulin resistance (OIR). In light of this evidence, the current proposal will address: 1- how adipose tissue lipolysis response to intestinal fermentation is affected by insulin resistance; 2- whether changes in ATL, observed when fermentation occurs, are also associated with a reduction of glycerol derived neo-gluconeogenesis; 3- if physical activity may restore the entero-endocrine and adipose tissue response to intestinal fermentation in youth with insulin resistance. This is the first study to test the effect of insulin resistance on the relationship between intestinal microbial metabolic activity and human metabolism (namely adipose tissue lipolysis, gluconeogenesis and entero-endocrine response). The results obtained will provide fundamental insight into how insulin resistance occurring in youth with obesity affects the metabolic response to fermentable carbohydrates. In fact, despite the large body of literature showing an association between intestinal microbial fermentation and human metabolism, how and whether insulin resistance may modulate this association remains unknown.

Conditions

Obesity and Overweight; Insulin Resistance; Obesity and Obesity-related Medical Conditions

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Remote physical exercise

Group Type: EXPERIMENTAL

Lactulose Oral Product

Intervention Type: OTHER

Each arm will undergo a study to induce colonic fermentation through lactulose at the beginning and at the end of the 12 weeks.

Control physical exercise

Group Type: ACTIVE_COMPARATOR

Lactulose Oral Product

Intervention Type: OTHER

Each arm will undergo a study to induce colonic fermentation through lactulose at the beginning and at the end of the 12 weeks.

Interventions

Lactulose Oral Product

Each arm will undergo a study to induce colonic fermentation through lactulose at the beginning and at the end of the 12 weeks.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age 15 to 22 years
• In puberty (girls and boys: Tanner stage III-V);
• BMI >85th

Exclusion Criteria

• Pregnancy;
• endocrinopathies (e.g., Cushing syndrome);
• substance abuse;
• medications affecting insulin resistance such as metformin, GLP-1 analogues; -
• high fibers intake (> 30g/day) as assessed by a 3-day food record.

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 22 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

NICOLA SANTORO, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale University

New Haven, Connecticut, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

NICOLA SANTORO, MD, PhD

Role: CONTACT

nicola.santoro@yale.edu

2037852819

Other Identifiers

R01DK140672

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000038988

Identifier Type: -

Identifier Source: org_study_id