Hepatic and Cardiac Metabolic Flexibility in Obese With NAFLD.

NCT03583437 | Completed

• 1 other identifier: jeyanrk
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Non-alcoholic fatty liver disease (NAFLD) covers a spectrum from reversible hepatic steatosis to inflammation and fibrosis termed steatohepatitis (NASH) and cirrhosis. New evidence indicates that NAFLD is associated with development of heart failure, abnormal ventricular glucose and fatty acid (FA) utilisation and cardiosteatosis. The mechanisms behind cardiac involvement and the progression from NAFLD to NASH are poorly understood but must include altered cardiac and intrahepatic lipid handling. In collaboration with renowned research groups from Oxford, Mayo Clinic and Copenhagen investigators plan comprehensive kinetic studies of heart and liver FA uptake and oxidation, ventricular function and substrate utilisation, and hepatic triglyceride (TG) secretion in order to assess mechanisms governing cardiac and hepatic lipid and glucose trafficking in subjects with NAFLD and NASH and the relationship with heart function. In addition, the investigators will assess skeletal muscle and adipose tissue enzyme activities, gene expression and protein concentrations in these subjects to define mechanisms involved in the cross-talk between heart, liver, muscle and adipose tissues. Investigators will address these questions using innovative tracer techniques (11Cpalmitate, 11C acetate, 18FDG glucose PET tracers and TG tracers) in combination with hepatic vein catherisation to study cardiac and liver substrate trafficking, as well as NMR spectroscopy, echocardiography, muscle and fat biopsies in combination with state-of-the art muscle and adipose tissue enzyme kinetics, gene- and protein expression. Effects of acute exercise will be assessed. The overarching goals are to define abnormalities and differences between NAFLD and NASH in hepatic lipid (FA and TG) metabolism and to assess the effect of exercise on both hepatic, cardiac and adipose and skeletal muscle lipid and substrate utilisation.

Conditions

NAFLD - Nonalcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (1)

• The effect of physical activity on the heart's metabolism of fatty acids in obese with and without NAFLD

  Primary outcome: \- Fatty acid uptake (mg/kg/min) in the Heart in obese with and without NAFLD

  2 years

Secondary Outcomes (1)

• To determine the effect of an acute exercise bout on the improvement of cardiac FA utilization in obese with and without NAFLD.

  2 years

Study Arms (2)

Healthy male volunteers

EXPERIMENTAL

Behavioral: Exercise Moderate Intensity Exercise (50 % af VO2max) for 90 minutes before and after PET scanning.

Behavioral: Exercise

Healthy female volunteers

EXPERIMENTAL

Behavioral: Exercise Moderate Intensity Exercise (50 % af VO2max) for 90 minutes before and after PET scanning.

Behavioral: Exercise

Interventions

Exercise BEHAVIORAL

Moderate Intensity Exercise (50 % af VO2max) for 90 minutes

Healthy female volunteers; Healthy male volunteers

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• obese subject men/women with NAFLD (MR spectroskopi, fibro scanner) (BMI \> 30).
• obese subject men/women without NAFLD (MR spectroskopi, fibro scanner) (BMI \> 30).
• age between 40-70 years
• Written consent before the start of the study

You may not qualify if:

• known current disease
• Fixed Medical drug consumption, statins and antihypertensive drugs (non-beta blocker). However, pause 3 weeks before the examination date
• Blood donation within the last 3 months prior to the study
• Participation in experiments involving radioactive isotopes within the last 6 months
• Alcohol abuse (over 21 items per week for men and 14 for women)
• Smoking
• Weight over 130 kg
• Cancer patients
• Large intake of medication

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Department of Diabetes and Hormone diseases in Aarhus University Hopital

Skejby, Aarhus N, 8200, Denmark

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Exercise

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Design

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

Model Details: Experimental: 1 Healthy male volunteers Behavioral: Exercise Moderate Intensity Exercise (50 % af VO2max) for 90 minutes before and after PET scanning, Experimental: 2 Healthy female volunteers Moderate Intensity Exercise (50 % af VO2max) for 90 minutes before and after a PET scanning.

Study Record Dates

• First Submitted: May 22, 2018
• First Posted: July 11, 2018
• Study Start: September 3, 2018
• Primary Completion: September 7, 2020
• Study Completion: May 23, 2022
• Last Updated: May 24, 2022

Record last verified: 2022-05

Locations

DK (1)