New Mechanisms of Obesity
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Lactulose Oral Product.
- Who it may be relevant to
- Registry conditions: Obesity and Overweight, Insulin Resistance, Obesity and Obesity-related Medical Conditions. Basic parameters: 15 years — 22 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Pathogenic Mechanisms of Obesity and Its Cardiometabolic Complications
Overview
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.
Interventions
- 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.
Primary outcome measures
- CHANGES IN ADIPOSE TISSUE LIPOLYSIS (ATL) [Time frame: 6 hours]
- CHANGES IN GLUCONEOGENESIS [Time frame: 6 hours]
- CHANGES IN ADIPOSE TISSUE LIPOLYSIS (ATL) [Time frame: Baseline and 12 weeks]
Secondary outcome measures (2)
- CHANGES IN PEPTIDE YY (PYY) concentration [Time frame: Baseline and 12 weeks]
- CHANGES IN GHRELIN concentration [Time frame: Baseline and 12 weeks]
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Basic science
Study locations
United States · 1 center
- Yale University — New Haven
Identifiers
NCT: NCT06768827 · 2000038988 · R01DK140672