Mechanisms of Obesity and Its Metabolic Complications in Youth

NCT03454828 | Completed Results DMC

• 2 other identifiers: 20000222391R01DK114504-01A1
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity, Childhood

Outcome Measures

Primary Outcomes (3)

• Rate of Appearance of Acetate

  Starting at 08:00, we began a 10-h, primed, continuous, peripheral venous infusion of 99% sodium \[d3\]-acetate with a priming dose of 200 μg · kg-1 · min-1 for 4 min and a continuous infusion rate of 59.5 μg · kg-1 · min-1 for 10 h. After 180 min from the start of the infusion, subjects received 20 g of lactulose per os, dissolved in 30 mL of water.

  Pre lactulose (average values at 2, 2.5, 3 hours) and Post lactulose (average of values at 7, 8, 9 and 10 hours)

• Percent of Hepatic de Novo Lipogenesis.

  The percent of hepatic de novo lipogenesis (DNL) refers to the proportion of fatty acids in the liver that are derived from a de novo synthesis pathway, rather than from dietary sources.

  Pre lactulose (average values at 2, 2.5, 3 hours) and Post lactulose (average of values at 7, 8, 9 and 10 hours)

• Change in the Rate of Appearance of Acetate

  The changes in rate of appearance of acetate (RaAcetate) are measured averaging the basal RaAcetate 9 timepoints (2 and 3 hours) and the post-lactulose RaAcetate (timepoints 7, 8, 9 and 10 hours).

  Pre lactulose (average values at 2, 2.5, 3 hours) and Post lactulose (average of values at 7, 8, 9 and 10 hours)

Study Arms (2)

obese carbohydrate diet

EXPERIMENTAL

Obese adolescents with a body mass index (BMI) \>95th percentile.

Dietary Supplement: obese carbohydrate diet

lean carbohydrate diet

ACTIVE COMPARATOR

Lean adolescents with a body mass index (BMI) \<85th percentile.

Dietary Supplement: lean carbohydrate diet

Interventions

obese carbohydrate diet DIETARY_SUPPLEMENT

The experimental diet will consist of 30% carbohydrates (CHO), 35% protein, and 35% fat. Since the experimental diet is lower in CHO, the fiber and sugar content will be calculated based on total CHO in the same percentage as the control (0.25 g fiber per each kcal of CHO and 18.2% sugar for total CHO).

obese carbohydrate diet

lean carbohydrate diet DIETARY_SUPPLEMENT

The control diet composition will follow the American Dietary Guidelines of 55% carbohydrates (CHO), 15% protein, and 30% fat. CHO content will be primarily complex CHO of high quality (14 g fiber/1,000 kcals and \<10% of total kcals in the form of sugar).

lean carbohydrate diet

Eligibility Criteria

• Age: 15 Years - 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (1)

Hospital Research Unit

New Haven, Connecticut, 06520, United States

Location

Related Publications (3)

• Galuppo B, Umano GR, Li Z, Van Name M, Samuels SL, Kien CL, Cline GW, Wagner DA, Barbieri E, Trico D, Santoro N. Comparison of Metabolic Response to Colonic Fermentation in Lean Youth vs Youth With Obesity. JAMA Netw Open. 2023 May 1;6(5):e2312530. doi: 10.1001/jamanetworkopen.2023.12530.

  PMID: 37159195 DERIVED

• Galuppo B, Cline G, Van Name M, Shabanova V, Wagner D, Kien CL, Santoro N. Colonic Fermentation and Acetate Production in Youth with and without Obesity. J Nutr. 2021 Nov 2;151(11):3292-3298. doi: 10.1093/jn/nxab277.

  PMID: 34494088 DERIVED

• Monga Kravetz A, Testerman T, Galuppo B, Graf J, Pierpont B, Siebel S, Feinn R, Santoro N. Effect of Gut Microbiota and PNPLA3 rs738409 Variant on Nonalcoholic Fatty Liver Disease (NAFLD) in Obese Youth. J Clin Endocrinol Metab. 2020 Oct 1;105(10):e3575-85. doi: 10.1210/clinem/dgaa382.

  PMID: 32561908 DERIVED

MeSH Terms

Conditions

Pediatric Obesity

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The study included a relatively small cohort of participants, which may limit the statistical power and generalizability of the findings. Differences in gut microbiota composition were not evaluated.

Results Point of Contact

• Title: Nicola Santoro
• Organization: Yale University School of Medicine: Pediatrics Endocrinology

nicola.santoro@yale.edu

2037376356

Study Officials

• Nicola Santoro, Phd,MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: February 19, 2018
• First Posted: March 6, 2018
• Study Start: August 18, 2018
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: October 9, 2025
• Results First Posted: October 9, 2025

Record last verified: 2025-09

Locations

US (1)