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

NCT ID: NCT01834300

Last Updated: 2024-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-01-01

Study Completion Date

2013-04-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Non Alcoholic Fatty Liver Disease

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Control

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.

Group Type EXPERIMENTAL

Unsupervised exercise training

Intervention Type 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.

lifestyle counseling and exercise

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.

Group Type EXPERIMENTAL

Supervised exercise training

Intervention Type 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.

Interventions

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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.

Intervention Type BEHAVIORAL

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.

Intervention Type BEHAVIORAL

Eligibility Criteria

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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 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
Minimum Eligible Age

20 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Royal Liverpool University Hospital

OTHER_GOV

Sponsor Role collaborator

University of Surrey

OTHER

Sponsor Role collaborator

Imperial College London

OTHER

Sponsor Role collaborator

Royal Surrey County Hospital NHS Foundation Trust

OTHER

Sponsor Role collaborator

University of Liverpool

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Daniel Cuthbertson, BSc PhD MRCP

Role: STUDY_DIRECTOR

University of Liverpool

Fariba Shojaee-Moradie, BSc PhD

Role: PRINCIPAL_INVESTIGATOR

University of Surrey

Locations

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Royal Surrey County Hospital

Guildford, Surrey, United Kingdom

Site Status

University of Surrey

Guildford, Surrey, United Kingdom

Site Status

John Moores University

Liverpool, , United Kingdom

Site Status

University of Liverpool

Liverpool, , United Kingdom

Site Status

Royal Liverpool University Hospital

Liverpool, , United Kingdom

Site Status

Liverpool University

Liverpool, , United Kingdom

Site Status

Imperial College London

London, , United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type DERIVED
PMID: 27583475 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27439593 (View on PubMed)

Other Identifiers

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09/H1008/1

Identifier Type: -

Identifier Source: org_study_id