New Mechanisms of Obesity (NMoO)

January 26, 2026 updated by: Yale University

Pathogenic Mechanisms of Obesity and Its Cardiometabolic Complications

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
55

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale University

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

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.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Remote physical exercise
Other: 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.
Active Comparator: Control physical exercise
Other: 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
CHANGES IN ADIPOSE TISSUE LIPOLYSIS (ATL)
Time Frame: 6 hours
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
Time Frame: 6 hours
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)
Time Frame: Baseline and 12 weeks
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
CHANGES IN PEPTIDE YY (PYY) concentration
Time Frame: Baseline and 12 weeks
Changes in PYY concentration after lactulose intervention will be compared between OIS and OIR.
Baseline and 12 weeks
CHANGES IN GHRELIN concentration
Time Frame: Baseline and 12 weeks
Changes in GHRELIN concentration after lactulose intervention will be compared between OIS and OIR.
Baseline and 12 weeks

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yale University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institutes of Health (NIH)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: NICOLA SANTORO, MD, PhD, Yale University

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 13, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 6, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 6, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 10, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 28, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 26, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2000038988
  • R01DK140672 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Published IPD will be shared at the end of the study

IPD Sharing Time Frame

a year after the completion of the study

IPD Sharing Access Criteria

Published IPD will be made available as an appendix to the paper published using the data generated through FigShare or other websites.

IPD Sharing Supporting Information Type

  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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