New Mechanisms of Obesity

NCT06768827 | Recruiting DMC

• 2 other identifiers: 2000038988R01DK140672
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Obesity; Youth; Insulin Resistance; Intestinal Fermentation

Outcome Measures

Primary Outcomes (3)

• CHANGES IN ADIPOSE TISSUE LIPOLYSIS (ATL)

  Changes in adipose tissue lipolysis occurring after colonic fermentation (stimulated by lactulose) will be compared between youth with obesity and insulin resistance (OIR) and with obesity and without insulin resistance (OIS). Lipolysis will be measured by using change in D5-glycerol concentration.

  6 hours

• CHANGES IN GLUCONEOGENESIS

  Gluconeogenesis (GLC) will be measured using change in deuterium oxide concentration after colonic fermentation due to lactulose ingestion and compared between OIS and OIR.

  6 hours

• CHANGES IN ADIPOSE TISSUE LIPOLYSIS (ATL)

  Changes in ATL due to colonic fermentation will be measured in two groups of OIR youth. One group will undergo physical activity for 12 weeks and another group will undergo a control intervention. Lipolysis will be measured by using change in D5-glycerol concentration.

  Baseline and 12 weeks

Secondary Outcomes (2)

• CHANGES IN PEPTIDE YY (PYY) concentration

  Baseline and 12 weeks

• CHANGES IN GHRELIN concentration

  Baseline and 12 weeks

Study Arms (2)

Remote physical exercise

EXPERIMENTAL

Other: Lactulose Oral Product

Control physical exercise

ACTIVE COMPARATOR

Other: Lactulose Oral Product

Interventions

Lactulose Oral Product 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; Remote physical exercise

Eligibility Criteria

• Age: 15 Years - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06520, United States

RECRUITING

MeSH Terms

Conditions

Obesity; Overweight; Insulin Resistance

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Study Officials

• NICOLA SANTORO, MD, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NICOLA SANTORO, MD, PhD

CONTACT

2037852819; nicola.santoro@yale.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2025
• First Posted: January 10, 2025
• Study Start: November 13, 2025
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): March 31, 2030
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: a year after the completion of the study
• Access Criteria: Published IPD will be made available as an appendix to the paper published using the data generated through FigShare or other websites.

Locations

US (1)