Obesity and OverweightNMoONCT06768827
New Mechanisms of Obesity
A study testing Lactulose Oral Product in people with Obesity and Overweight and Insulin Resistance, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 15 to 22 years
- Conditions the study is for
- Obesity and Overweight, Insulin Resistance, Obesity and Obesity-related Medical Conditions
- What is being tested?
- Lactulose Oral Product
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Nov 2025to 31 Mar 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 22 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age 15 to 22 years
- In puberty (girls and boys: Tanner stage III-V);
- BMI >85th
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Yale University
New Haven, Connecticut, 06520
About this study
Official title: 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.
Read the 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
- Being tested
- Lactulose Oral Product
- Keywords
- Obesity, Youth, Insulin Resistance, Intestinal Fermentation
- Medical subject headings
- Obesity, Overweight, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lactulose Oral ProductOther
Each arm will undergo a study to induce colonic fermentation through lactulose at the beginning and at the end of the 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Remote physical exercise | Experimental | Not described Receives: Other: Lactulose Oral Product |
| Control physical exercise | Active comparator | Not described Receives: Other: Lactulose Oral Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Baseline and 12 weeks
Secondary outcomes (2)
CHANGES IN PEPTIDE YY (PYY) concentration
Changes in PYY concentration after lactulose intervention will be compared between OIS and OIR.
Measured: Baseline and 12 weeks
CHANGES IN GHRELIN concentration
Changes in GHRELIN concentration after lactulose intervention will be compared between OIS and OIR.
Measured: Baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2025
- Study start13 Nov 2025
- Primary completion31 Mar 2030 (estimated)
- Study completion31 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Obesity and OverweightStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor
- Investigators
- NICOLA SANTORO, MD, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06768827
- Sponsor's protocol ID
- 2000038988
- Other IDs
- R01DK140672
- Acronym
- NMoO
- Status last verified
- Jan 2026
- First submitted
- 6 Jan 2025
- Last updated
- 28 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Published IPD will be shared at the end of the study
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pathogenic Mechanisms of Obesity and Its Cardiometabolic Complications
- ClinicalTrials.gov ID
- NCT06768827
- Acronym / sponsor ID
- NMoO / 2000038988
- Conditions
- Obesity and Overweight, Insulin Resistance, Obesity and Obesity-related Medical Conditions
- Keywords
- Obesity, Youth, Insulin Resistance, Intestinal Fermentation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 13 Nov 2025 (actual)
- Primary completion
- 31 Mar 2030 (estimated)
- Study completion
- 31 Mar 2030 (estimated)
- First posted
- 10 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Remote physical exercise | Experimental | Other: Lactulose Oral Product |
| Control physical exercise | Active comparator | Other: Lactulose Oral Product |
Who may qualify
- Ages
- 15 to 22 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Age 15 to 22 years
- In puberty (girls and boys: Tanner stage III-V);
- BMI >85th
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lactulose Oral ProductEach arm will undergo a study to induce colonic fermentation through lactulose at the beginning and at the end of the 12 weeks. | Other | Control physical exercise, Remote physical exercise |
Primary outcome
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.
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.
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.
2 secondary outcomes
CHANGES IN PEPTIDE YY (PYY) concentration
Time frame: Baseline and 12 weeks
CHANGES IN GHRELIN concentration
Time frame: Baseline and 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2026.
- Individual participant dataSharing planned: Yes. Published IPD will be shared at the end of the study
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
NICOLA SANTORO, MD, PhD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lactulose Oral Product in people with Obesity and Overweight and Insulin Resistance, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact NICOLA SANTORO, MD, PhD (2037852819, nicola.santoro@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CHANGES IN ADIPOSE TISSUE LIPOLYSIS (ATL) (time frame: 6 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2026.