Hepatic Mitochondrial Function in Youth

Active, not recruiting

• Conditions: Bariatric Surgery Candidate; Obesity; Adolescent Obesity; Hepatic Steatosis

• Registration Number: NCT03587727
• Lead Sponsor: University of Colorado, Denver

Brief Summary

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

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 Timeline

• Study First Submitted: 2018-06-14
• Study First Submitted QC: 2018-07-02
• Study First Posted: 2018-07-16
• Study Start: 2018-11-20
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-17
• Last Update Posted: 2024-04-19
• Primary Completion: 2024-06-30
• Study Completion: 2024-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percent Change in Liver Fat per MRI	Prior to bariatric surgery and 1 year post-bariatric surgery	Change from baseline in percent hepatic fat measured with MRI and calculated via the Dixon method as the proton density hepatic fat, which ranges from 0-75%.
Change in %Direct TG-Glycerol Appearance	Prior to bariatric surgery and 1 year post-bariatric surgery	Change in %TG-Glycerol appearance from a labeled glycerol drink via direct pathway.

Secondary Outcome Measures

Name	Time	Method
Baseline Hepatic Steatosis Score via Tissue	At the time of surgery	NAFLD Activity Score (NAS) determined via liver tissue biopsy. The NAS can range from 0 to 8 and is calculated by the sum of scores of steatosis (0-3), lobular inflammation (0-3) and hepatocyte ballooning (0-2). In patients with NAFLD, NAS score of ≥ 5 strongly correlated with a diagnosis of "definite NASH" whereas NAS ≤ 3 correlated with a diagnosis of "not NASH".
Change in Minimum Insulin	Prior to bariatric surgery and 1 year post-bariatric surgery	Mixed meal tolerance test (MMTT): Minimum insulin concentration (uIU/mL) during 4 hour MMTT with 13 time points.
Change in Peak C-peptide	Prior to bariatric surgery and 1 year post-bariatric surgery	Mixed meal tolerance test (MMTT): Peak c-peptide concentration (ng/mL) during 4 hour MMTT with 10 time points.
Change in Fasting Glucagon	At time of surgery	Mixed meal tolerance test (MMT): Fasting glucagon concentration (pg/mL) at the beginning of a 4 hour MMTT.
Mitochondrial Function in the Liver Assessed by Oroboros	At the time of surgery	L/E Coupling Control Ratio: Maximal respiratory capacity was examined in permeabilized hepatic tissue from adolescents using pyruvate (carbohydrate) and palmitoylcarnitine (lipid) as a substrate. Respiratory capacity was normalized to hepatic tissue wet weight. Coupling control ratio (L/E) was calculated as oxygen flux in leak (oligomyocin) divided by ET capacity (FCCP) with a maximum coupling of 1.0.
Change in Peak Glucose	Prior to bariatric surgery and 1 year post-bariatric surgery	Mixed meal tolerance test (MMTT): Peak glucose concentration (mg/dL) during 4 hour MMTT with 16 time points.
Change in Insulin Sensitivity	Prior to bariatric surgery and 1 year post-bariatric surgery	Mixed meal tolerance test (MMTT): measured with SI. This is a measure of post-prandial (MMTT) insulin sensitivity as calculated with the Oral Minimal Model (OMM) using SAAM II Software.
Change in Peak GLP-1	Prior to bariatric surgery and 1 year post-bariatric surgery	Mixed meal tolerance test (MMTT): Peak GLP-1 concentration (pmol/L) during 4 hour MMTT with 9 time points.
Change in Minimum Glucose	Prior to bariatric surgery and 1 year post-bariatric surgery	Mixed meal tolerance test (MMTT): Minimum glucose concentration (mg/dL) during 4 hour MMTT with 16 time points.
Change in Peak Insulin	Prior to bariatric surgery and 1 year post-bariatric surgery	Mixed meal tolerance test (MMTT): Peak insulin concentration (uIU/mL) during 4 hour MMTT with 13 time points.
Change in Liver Stiffness per MRI	Prior to bariatric surgery and 1 year post-bariatric surgery	Change from baseline in degree of hepatic stiffness, measured with Magnetic Resonance elastography (MRE).

Trial Locations

Locations (1)

University of Colorado Anshutz Medical Campus/Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States