Hepatic Mitochondrial Function in Youth

Obesity Clinical Trial

— MANGO  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03587727
• Other study ID #: 18-0479
• Status: Active, not recruiting
• Start date: November 20, 2018
• Est. completion date: June 30, 2024

Study information

• Verified date: April 2024
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 19
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years to 20 Years

Eligibility

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-? or PPAR-a, 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

Related Conditions & MeSH terms

• Adolescent Obesity
• Bariatric Surgery Candidate
• Fatty Liver
• Hepatic Steatosis
• Obesity
• Pediatric Obesity

Locations

Country	Name	City	State
United States	University of Colorado Anshutz Medical Campus/Children's Hospital Colorado	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change in Liver Fat per MRI	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%.	Prior to bariatric surgery and 1 year post-bariatric surgery
Primary	Change in %Direct TG-Glycerol Appearance	Change in %TG-Glycerol appearance from a labeled glycerol drink via direct pathway.	Prior to bariatric surgery and 1 year post-bariatric surgery
Secondary	Change in Insulin Sensitivity	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.	Prior to bariatric surgery and 1 year post-bariatric surgery
Secondary	Change in Peak Glucose	Mixed meal tolerance test (MMTT): Peak glucose concentration (mg/dL) during 4 hour MMTT with 16 time points.	Prior to bariatric surgery and 1 year post-bariatric surgery
Secondary	Change in Minimum Glucose	Mixed meal tolerance test (MMTT): Minimum glucose concentration (mg/dL) during 4 hour MMTT with 16 time points.	Prior to bariatric surgery and 1 year post-bariatric surgery
Secondary	Change in Peak Insulin	Mixed meal tolerance test (MMTT): Peak insulin concentration (uIU/mL) during 4 hour MMTT with 13 time points.	Prior to bariatric surgery and 1 year post-bariatric surgery
Secondary	Change in Minimum Insulin	Mixed meal tolerance test (MMTT): Minimum insulin concentration (uIU/mL) during 4 hour MMTT with 13 time points.	Prior to bariatric surgery and 1 year post-bariatric surgery
Secondary	Change in Peak C-peptide	Mixed meal tolerance test (MMTT): Peak c-peptide concentration (ng/mL) during 4 hour MMTT with 10 time points.	Prior to bariatric surgery and 1 year post-bariatric surgery
Secondary	Change in Peak GLP-1	Mixed meal tolerance test (MMTT): Peak GLP-1 concentration (pmol/L) during 4 hour MMTT with 9 time points.	Prior to bariatric surgery and 1 year post-bariatric surgery
Secondary	Change in Fasting Glucagon	Mixed meal tolerance test (MMT): Fasting glucagon concentration (pg/mL) at the beginning of a 4 hour MMTT.	At time of surgery
Secondary	Change in Liver Stiffness per MRI	Change from baseline in degree of hepatic stiffness, measured with Magnetic Resonance elastography (MRE).	Prior to bariatric surgery and 1 year post-bariatric surgery
Secondary	Mitochondrial Function in the Liver Assessed by Oroboros	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.	At the time of surgery
Secondary	Baseline Hepatic Steatosis Score via Tissue	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".	At the time of surgery