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

NCT01834300 | Completed DMC

• 1 other identifier: 09/H1008/1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Non Alcoholic Fatty Liver Disease

Keywords

Hepatic insulin sensitivity; Muscle insulin sensitivity; B cell function; VLDL1 TG metabolism; VLDL2 TG metabolism

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Changes in liver function tests

  4 months

• Changes in lipid profiles

  4 months

• Changes in body weight and anthropometric measurements

  4 months

• Hepatic insulin sensitivity

  4 months

• VLDL-TG kinetics

  4 months

Study Arms (2)

Control

EXPERIMENTAL

Unsupervised exercise training This group will be given 1 hour lifestyle counseling by the exercise trainer after which they will have no contact with the exercise trainer to the end of the intervention period. The exercise intervention will be offered to the subjects once the post studies are completed.

Behavioral: Unsupervised exercise training

lifestyle counseling and exercise

EXPERIMENTAL

Supervised exercise training Four months exercise training intervention will be either gym-based or patients will choose the mode of exercise that suits their lifestyle. 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.

Behavioral: Supervised exercise training

Interventions

Unsupervised exercise training BEHAVIORAL

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.

Control

Supervised exercise training BEHAVIORAL

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.

lifestyle counseling and exercise

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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 β-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

Sponsors & Collaborators

• University of Liverpool: lead
• Royal Liverpool University Hospital: collaborator
• University of Surrey: collaborator
• Imperial College London: collaborator
• Royal Surrey County Hospital NHS Foundation Trust: collaborator

Study Sites (7)

Royal Surrey County Hospital

Guildford, Surrey, GU16 7UJ, United Kingdom

Location

University of Surrey

Guildford, Surrey, GU27WG, United Kingdom

Location

John Moores University

Liverpool, L3 2ET, United Kingdom

Location

University of Liverpool

Liverpool, L69 3GE, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

Liverpool University

Liverpool, L9 7AL, United Kingdom

Location

Imperial College London

London, W12 0HS, United Kingdom

Location

Related Publications (2)

• Shojaee-Moradie F, Cuthbertson DJ, Barrett M, Jackson NC, Herring R, Thomas EL, Bell J, Kemp GJ, Wright J, Umpleby AM. Exercise Training Reduces Liver Fat and Increases Rates of VLDL Clearance But Not VLDL Production in NAFLD. J Clin Endocrinol Metab. 2016 Nov;101(11):4219-4228. doi: 10.1210/jc.2016-2353. Epub 2016 Sep 1.

  PMID: 27583475 DERIVED

• Pugh CJ, Sprung VS, Jones H, Richardson P, Shojaee-Moradie F, Umpleby AM, Green DJ, Cable NT, Trenell MI, Kemp GJ, Cuthbertson DJ. Exercise-induced improvements in liver fat and endothelial function are not sustained 12 months following cessation of exercise supervision in nonalcoholic fatty liver disease. Int J Obes (Lond). 2016 Dec;40(12):1927-1930. doi: 10.1038/ijo.2016.123. Epub 2016 Jul 21.

  PMID: 27439593 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Daniel Cuthbertson, BSc PhD MRCP

  University of Liverpool

  STUDY DIRECTOR

• Fariba Shojaee-Moradie, BSc PhD

  University of Surrey

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 12, 2013
• First Posted: April 17, 2013
• Study Start: January 1, 2009
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: December 18, 2024

Record last verified: 2024-05

Locations

GB (7)