MANGO: Hepatic Mitochondrial Function in Youth

Sponsor

University of Colorado, Denver (Other)

Overall Status

Recruiting

CT.gov ID

NCT03587727

Collaborator

(none)

Enrollment

Location

55.3

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Assess the impact of bariatric surgery on hepatic energy metabolism and glucose and insulin dynamics in obese youth

Condition or Disease	Intervention/Treatment	Phase
Hepatic Steatosis Bariatric Surgery Candidate Adolescent Obesity Obesity

Detailed Description

A metabolic study that will be performed prior to and 12 months following bariatric surgery. The study will include 31-phosphorus magnetic resonance spectroscopy to measure phosphate concentrations in the liver; a 4 hour mixed meal tolerance test, an intravenous arginine test, Abdominal Magnetic Resonance Imaging (MRI) for visceral and hepatic fat, Magnetic Resonance (MR) Elastography of the liver, indirect calorimetry, body composition assessment with Bodpod, serum metabolomics and hepatic tissue mitochondrial measures from the time of surgery only.

Study Design

Study Type:

Observational

Anticipated Enrollment :

25 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Hepatic Fat Content and Mitochondrial Flux in Obese Youth Before and After Bariatric Surgery

Actual Study Start Date :

Nov 20, 2018

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Jun 30, 2023

Outcome Measures

Primary Outcome Measures

Changes in Hepatic mitochondrial function [Prior to bariatric surgery and 1 year post-bariatric surgery]
Hepatic mitochondrial function will be measured with 31 phosphorus MR Spectroscopy: Hepatic mitochondrial function
Changes in Hepatic mitochondrial function [Prior to bariatric surgery and 1 year post-bariatric surgery]
Hepatic mitochondrial function will be measured with 31 phosphorus MR Spectroscopy Magnetic Resonance Imaging: MRE, hepatic fat fraction.

Secondary Outcome Measures

Changes in Insulin Resistance/pancreas/GI hormones [Prior to bariatric surgery and 1 year post-bariatric surgery]
Mixed meal tolerance test (MMT): Insulin sensitivity to determine maximal insulin secretion.
Changes in Insulin Resistance/pancreas/GI hormones [Prior to bariatric surgery and 1 year post-bariatric surgery]
Mixed meal tolerance test (MMT): Hyperglycemia to determine maximal insulin secretion
Changes in Insulin Resistance/pancreas/GI hormones [Prior to bariatric surgery and 1 year post-bariatric surgery]
Mixed meal tolerance test (MMT): Hypoglycemia to determine maximal insulin secretion
Changes in Insulin Resistance/pancreas/GI hormones [Prior to bariatric surgery and 1 year post-bariatric surgery]
Mixed meal tolerance test (MMT): Insulin/C-peptide response to determine maximal insulin secretion
Changes in Insulin Resistance/pancreas/GI hormones [Prior to bariatric surgery and 1 year post-bariatric surgery]
Mixed meal tolerance test (MMT): GLP-1 to determine maximal insulin secretion
Insulin Resistance/pancreas/GI hormones [Prior to bariatric surgery and 1 year post-bariatric surgery]
Mixed meal tolerance test (MMT): Glucagon response to determine maximal insulin secretion
NAFLD via MRI [Prior to bariatric surgery and 1 year post-bariatric surgery]
Changes, if any, will be documented through the use of Magnetic Resonance (MR) elastography.
Changes in Tissue hepatic glycerol flux [At time of surgery]
Glucose will be assessed with Oroboros, isotopomer flux will be determined by 13c glycerol tracer
Changes in Tissue hepatic mitochondrial function [At time of surgery]
Fat oxidation will be assessed with Oroboros
Changes in NAFLD status via tissue [At time of surgery]
NAFLD status will be determined by biopsy at the time of surgery

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years to 20 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Obese youth ages 13-20 years, scheduled for bariatric surgery at Children's Hospital Colorado
BMI 35-55 m2/kg
Maximal body circumference <200 cm

Exclusion Criteria:

Use of medications known to affect insulin sensitivity: oral glucocorticoids within 10; days, atypical antipsychotics, immunosuppressant agents, HIV medications.
Infectious hepatitis
Alcohol abuse
Mitochondrial disease
Type 2 diabetes
Medications that affect hepatic outcomes (e.g. PPAR-γ or PPAR-α, metformin)
Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study.
Severe illness requiring hospitalization within 60 days
Diabetes, defined as Hemoglobin A1C > 6.4%
Anemia, defined as Hemoglobin < 10 mg/dL
Diagnosed major psychiatric or developmental disorder limiting informed consent
Implanted metal devices that are not compatible with MRI