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Mechanisms of Obesity and Its Metabolic Complications in Youth

Primary Purpose

Obesity, Childhood

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
obese carbohydrate diet
lean carbohydrate diet
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obesity, Childhood

Eligibility Criteria

15 Years - 21 Years (Child, Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Hospital Research UnitRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

obese carbohydrate diet

lean carbohydrate diet

Arm Description

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

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

Outcomes

Primary Outcome Measures

For an equal amount of dietary carbohydrates, obese youth will synthesize short chain fatty acids at higher rates than lean youth.
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.
If high rates of short chain fatty acid (SCFA) synthesis enhance hepatic de novo lipogenesis.
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).
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.

Secondary Outcome Measures

Full Information

First Posted
February 19, 2018
Last Updated
May 4, 2023
Sponsor
Yale University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT03454828
Brief Title
Mechanisms of Obesity and Its Metabolic Complications in Youth
Official Title
Mechanisms of Obesity and Its Metabolic Complications in Youth
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2018 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

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.
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Childhood

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
obese carbohydrate diet
Arm Type
Experimental
Arm Description
Obese adolescents with a body mass index (BMI) >95th percentile.
Arm Title
lean carbohydrate diet
Arm Type
Active Comparator
Arm Description
Lean adolescents with a body mass index (BMI) <85th percentile.
Intervention Type
Dietary Supplement
Intervention Name(s)
obese carbohydrate diet
Intervention Description
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).
Intervention Type
Dietary Supplement
Intervention Name(s)
lean carbohydrate diet
Intervention Description
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).
Primary Outcome Measure Information:
Title
For an equal amount of dietary carbohydrates, obese youth will synthesize short chain fatty acids at higher rates than lean youth.
Description
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.
Time Frame
4 hours
Title
If high rates of short chain fatty acid (SCFA) synthesis enhance hepatic de novo lipogenesis.
Description
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.
Time Frame
12 hours
Title
The effect of an isocaloric low carbohydrate (CHO) diet on the bacterial synthesis of short chain fatty acids (SCFA).
Description
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.
Time Frame
1 week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nicola Santoro, PhD,MD
Phone
203-737-6356
Email
nicola.santoro@yale.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicola Santoro, Phd,MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Research Unit
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicola Santoro

12. IPD Sharing Statement

Citations:
PubMed Identifier
34494088
Citation
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.
Results Reference
derived
PubMed Identifier
32561908
Citation
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.
Results Reference
derived

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Mechanisms of Obesity and Its Metabolic Complications in Youth

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