Mechanisms of Obesity and Its Metabolic Complications in Youth

Not Applicable

Completed

• Conditions: Obesity, Childhood
• Interventions: Dietary Supplement: lean carbohydrate diet; Dietary Supplement: obese carbohydrate diet

• Registration Number: NCT03454828
• Lead Sponsor: Yale University

Brief Summary

The overarching goal of this project is to determine whether the effect of gut microbiota on human metabolism might be mediated by short chain fatty acids (SCFA) and whether the SCFA might modulate lipid metabolism.

Detailed Description

This would be the first study determining the effect of SCFA synthesis on hepatic de novo lipogenesis and to assess whether and how isocaloric dietary changes (namely low carbohydrates) might modify the composition of the gut microbiota and reduce the synthesis of SCFA during adolescence, a sensitive period for the development of obesity.

Study Timeline

• Study First Submitted: 2018-02-19
• Study First Submitted QC: 2018-02-26
• Study First Posted: 2018-03-06
• Study Start: 2018-08-18
• Primary Completion: 2024-06-30
• Study Completion: 2024-06-30
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-27
• Last Update Posted: 2024-10-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 85

Inclusion Criteria

• Good general health,
• Taking no medication on a chronic basis
• Age 15 to 21 years,
• In puberty (girls and boys: Tanner stage III - V)
• BMI >25th and <85th for lean cohort; BMI >95th for obese cohort
• Girls who begin menstruating must have a negative pregnancy test during the study.

Exclusion criteria:

• Baseline creatinine >1.0 mg
• Food allergies
• Pregnancy
• Presence of endocrinopathies (e.g. Cushing syndrome)
• Significant chronic illness.

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
lean carbohydrate diet	lean carbohydrate diet	Lean adolescents with a body mass index (BMI) \<85th percentile.
obese carbohydrate diet	obese carbohydrate diet	Obese adolescents with a body mass index (BMI) \>95th percentile.

Primary Outcome Measures

Name	Time	Method
If high rates of short chain fatty acid (SCFA) synthesis enhance hepatic de novo lipogenesis.	12 hours	Subjects will consume 2g of Inulin, 13g of unlabeled inulin. Blood draws will be taken every hour. To evaluate the association between total SCFA and de novo lipogenesis, peak percent changes in de novo lipogenesis will be regressed on peak percent changes in total SCFA.
The effect of an isocaloric low carbohydrate (CHO) diet on the bacterial synthesis of short chain fatty acids (SCFA).	1 week	Subjects will be enrolled in a low carbohydrate diet. The percent change in peak total acetate rate, calculated as the follow-up peak total acetate minus the baseline peak total acetate divided by the baseline peak total acetate, will be compared between the low CHO period and the control period.
For an equal amount of dietary carbohydrates, obese youth will synthesize short chain fatty acids at higher rates than lean youth.	4 hours	Subjects will be given orally 15g of deuterated inulin every 30 minutes.Total acetate is calculated by summing the synthetic rates of the single acetate. The primary outcome will be the peak percent change from fasting in total acetate estimated by dividing the difference between total acetate at fasting and the peak total acetate by the total acetate at fasting.

Trial Locations

Locations (1)

Hospital Research Unit; 🇺🇸 New Haven, Connecticut, United States