Non Alcoholic Fatty Liver DiseaseNCT01834300
The Effect of Exercise Intervention on Insulin Resistance in Non-alcoholic Fatty Liver Disease (NAFLD)
A study testing Unsupervised exercise training and Supervised exercise training in people with Non Alcoholic Fatty Liver Disease, run by University of Liverpool at 7 sites in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- Non Alcoholic Fatty Liver Disease
- What is being tested?
- Unsupervised exercise training and Supervised exercise training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 7 sitesUnited Kingdom
- Study dates
- 1 Jan 2009to 1 Apr 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United Kingdom7 sites
Royal Surrey County Hospital
Guildford, Surrey, GU16 7UJ
University of Surrey
Guildford, Surrey, GU27WG
John Moores University
Liverpool, L3 2ET
University of Liverpool
Liverpool, L69 3GE
Royal Liverpool University Hospital
Liverpool, L7 8XP
Liverpool University
Liverpool, L9 7AL
Imperial College London
London, W12 0HS
About this study
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).
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.
Read the detailed description
- 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.
- 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.
- 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
- Non Alcoholic Fatty Liver Disease
- Being tested
- Unsupervised exercise training, Supervised exercise training
- Keywords
- Hepatic insulin sensitivity, Muscle insulin sensitivity, B cell function, VLDL1 TG metabolism, VLDL2 TG metabolism
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Unsupervised exercise trainingBehavioural
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 trainingBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Behavioral: Supervised exercise training |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 4 months
Secondary outcomes (5)
Changes in liver function tests
Biochemial measurements of the liver enzymes will be measured pre and post intervention period
Measured: 4 months
Changes in lipid profiles
Total cholesterol, triglyceride and high density lipoprotien concentrations in fasting state will be measured pre and post intervention period.
Measured: 4 months
Changes in body weight and anthropometric measurements
Body weight and waist to hip ratio will be measured pre and post intervention period.
Measured: 4 months
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
Measured: 4 months
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.
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2013 (estimated)
- Study start1 Jan 2009
- Primary completion1 Apr 2013
- Study completion1 Apr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Non Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Liverpool
- Sponsor type
- University, hospital or other
- Collaborators
- Royal Liverpool University Hospital, University of Surrey, Imperial College London, Royal Surrey County Hospital NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- Daniel Cuthbertson, BSc PhD MRCP, Study director, University of LiverpoolFariba Shojaee-Moradie, BSc PhD, Principal investigator, University of Surrey
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01834300
- Sponsor's protocol ID
- 09/H1008/1
- Status last verified
- May 2024
- First submitted
- 12 Apr 2013
- Last updated
- 18 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Cuthbertson DJ, Keating SE, Pugh CJA, Owen PJ, Kemp GJ, Umpleby M, Geyer NG, Chinchilli VM, Stine JG. Exercise improves surrogate measures of liver histological response in metabolic dysfunction-associated steatotic liver disease. Liver Int. 2024 Sep;44(9):2368-2381. doi: 10.1111/liv.15947. Epub 2024 Jun 7.
PubMed 38847589Shojaee-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.
PubMed 27583475Pugh 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.
PubMed 27439593
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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).
- ClinicalTrials.gov ID
- NCT01834300
- Acronym / sponsor ID
- 09/H1008/1
- Conditions
- Non Alcoholic Fatty Liver Disease
- Keywords
- Hepatic insulin sensitivity, Muscle insulin sensitivity, B cell function, VLDL1 TG metabolism, VLDL2 TG metabolism
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of LiverpoolUniversity, hospital or other
- Collaborators
- Royal Liverpool University Hospital, University of Surrey, Imperial College London, Royal Surrey County Hospital NHS Foundation Trust
- Study start
- 1 Jan 2009 (actual)
- Primary completion
- 1 Apr 2013 (actual)
- Study completion
- 1 Apr 2013 (actual)
- First posted
- 17 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- 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.
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Experimental | Behavioral: Unsupervised exercise trainingUnsupervised 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. |
| lifestyle counseling and exercise | Experimental | Behavioral: Supervised exercise trainingSupervised 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. |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Unsupervised exercise trainingThe 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. | Behavioural | Control |
| Supervised exercise trainingPatients 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. | Behavioural | lifestyle counseling and exercise |
Primary outcome
Reduction in liver and muscle fat
Time frame: 4 months
Tissue triglyceride content, or steatosis, will be accurately and non-invasively quantified in vivo using localized proton magnetic resonance spectroscopy (1H MRS).
5 secondary outcomes
Changes in liver function tests
Time frame: 4 months
Changes in lipid profiles
Time frame: 4 months
Changes in body weight and anthropometric measurements
Time frame: 4 months
Hepatic insulin sensitivity
Time frame: 4 months
VLDL-TG kinetics
Time frame: 4 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2024.
- Derived from this study: PubMed 38847589Cuthbertson DJ, Keating SE, Pugh CJA, Owen PJ, Kemp GJ, Umpleby M, Geyer NG, Chinchilli VM, Stine JG. Exercise improves surrogate measures of liver histological response in metabolic dysfunction-associated steatotic liver disease. Liver Int. 2024 Sep;44(9):2368-2381. doi: 10.1111/liv.15947. Epub 2024 Jun 7.
- Derived from this study: PubMed 27583475Shojaee-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.
- Derived from this study: PubMed 27439593Pugh 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Cuthbertson, BSc PhD MRCP study director
University of Liverpool
Fariba Shojaee-Moradie, BSc PhD principal investigator
University of Surrey
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Unsupervised exercise training and Supervised exercise training in people with Non Alcoholic Fatty Liver Disease, run by University of Liverpool at 7 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in liver and muscle fat (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01834300, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2024.