The Effect of Exercise Intervention on Insulin Resistance in Non-alcoholic Fatty Liver Disease (NAFLD)

Non Alcoholic Fatty Liver Disease Clinical Trial

Official title:

The Effects of Exercise Training on Visceral Fat, Insulin Sensitivity, β-cell Function and Triglyceride Kinetics in Patients With Non-alcoholic Fatty Liver Disease (NAFLD).

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01834300
• Other study ID #: 09/H1008/1
• Status: Active, not recruiting
• Phase: N/A
• First received: April 12, 2013
• Last updated: September 16, 2014
• Start date: February 2009
• Est. completion date: June 2015

Study information

• Verified date: September 2014
• Source: University of Liverpool
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

This project examines the effects of a 4 month structured exercise intervention program in patients with non-alcoholic fatty liver disease (NAFLD). We will examine changes in total and depot-specific (i.e.in different tissues, liver, muscle and pancreas)fat. We will correlate these with measurements of the insulin from the liver. The hypothesis is that by reducing fat in these specific depots we can reduce insulin resistance and prevent progression to diabetes.

Description:

1. Exercise program: We are asking people to take part in a supervised exercise program for 4 months. This involves on average a weekly supervised exercise bout plus other unsupervised exercise bouts at home. We will ensure participants are physically able to embark on this by taking their medical history, physical examination and validated questionnaire (PARQ). This program is for the benefit on the patients' long term health.

2. MR imaging to assess fat: occassionally these may pick up anomalies which require further investigation. A radiologist will screen the abdominal images and GP will be informed on anything requiring further investigation.

No radiation is received during MR imaging.

3. Physiological studies: Patients will be asked to attend for 2 non-consecutive days before and after the exercise intervention. Regular blood samples will be required as apart of these investigations.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: June 2015
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 65 Years

Eligibility

Inclusion Criteria:

• Sedentary, non smoking, male subjects,

• Alcohol consumption men <21 units/week,

• BMI 27-35. (Lean individuals do not suffer from NAFLD, so are not suitable for this study. Conversely, we are restricted to a maximum BMI of 35 due to the size limitations of the MR scanner.)

• A clinical diagnosis of NAFLD based upon the following criteria: i) exclusion of other causes of liver disease i.e. negative Hepatitis B and C serology, a negative auto-immune profile and normal caeruloplasmin concentrations, ii) Ultrasound appearances suggestive of a fatty, echo-bright liver with no evidence of cirrhosis (in some cases, the diagnosis will have been confirmed histologically after liver biopsy.

• Being willing to engage and motivated to follow an exercise program.

Exclusion Criteria:

• Prescription of corticosteroids, amiodarone, tamoxifen, methotrexate (drugs known to cause secondary steatohepatitis) or fibrates. Statin is Ok as long as the patients are on stable therapy for a while, if changed then the patient will be excluded.

• Alcohol consumption for men 21 units/week.

• A contraindication to exercise (such as unstable ischaemic heart disease),

• Type 2 diabetes (type 2 diabetes patients are excluded so that we are examining the involvement of insulin resistance at a reversible stage before ß-cell failure has occurred).

• Patients who are on medications that will interact with GTN (glyceryl trinitrate) will be excluded from the GTN dilatation (endothelial independent NO mediated function) aspect of the study.

• Individuals who suffer from claustrophobia and have metal implants will be excluded from the MRI aspect of the study.

• Patients who smoke will also be excluded from the study.

• Total cholesterol >7

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non Alcoholic Fatty Liver Disease

Intervention

Behavioral:
• Unsupervised exercise training
The patients will be given lecture on lifestyle changes and its benefitial effects on health at the begining of the study by the exercise trainer. There will be no conatct with the exercise trainer for the period of intervention for 4 months.
• Supervised exercise training
Patients will be encouraged to exercise four times per week for 30-45 min at 60-80 % of maximal heart rate, with a 5 min warm-up and warm-down. Participants will be given free access to a variety of affiliated sports centres and will use the Wellness Key system, a software program that enables researchers to remotely track the exercise activity of participants very accurately. To ensure compliance with rest or exercise, all participants of both groups will have their mean physical activity level in 2 non-consecutive weeks evaluated with an ambulatory accelerometer.

Locations

Country	Name	City	State
United Kingdom	Royal Surrey County Hospital	Guildford	Surrey
United Kingdom	University of Surrey	Guildford	Surrey
United Kingdom	John Moores University	Liverpool
United Kingdom	Liverpool University	Liverpool
United Kingdom	Royal Liverpool University Hospital	Liverpool
United Kingdom	University of Liverpool	Liverpool
United Kingdom	Imperial College London	London

Sponsors (5)

Lead Sponsor	Collaborator
University of Liverpool	Imperial College London, Royal Liverpool University Hospital, Royal Surrey County Hospital, University of Surrey

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in liver and muscle fat	Tissue triglyceride content, or steatosis, will be accurately and non-invasively quantified in vivo using localized proton magnetic resonance spectroscopy (1H MRS).	4 months	No
Secondary	Changes in liver function tests	Biochemial measurements of the liver enzymes will be measured pre and post intervention period	4 months	No
Secondary	Changes in lipid profiles	Total cholesterol, triglyceride and high density lipoprotien concentrations in fasting state will be measured pre and post intervention period.	4 months	No
Secondary	Changes in body weight and anthropometric measurements	Body weight and waist to hip ratio will be measured pre and post intervention period.	4 months	No
Secondary	Hepatic insulin sensitivity	Half of the study cohort i.e. 30 individuals,15 exercise and 15 controls, will have peripheral and hepatic insulin sensitivity determined using a two-stage hyperinsulinaemic, euglycaemic clamp and use of deuterated glucose (2H2-glucose	4 months	No
Secondary	VLDL-TG kinetics	The other half of the study cohort i.e. 30 individuals, 15 exercise and 15 controls, will have VLDL1 and VLDL2 TG kinetics determined using 5H2 glycerol bolus.	4 months	No