Non-alcoholic Fatty Liver DiseaseHELPNCT02526732
Hepatic Inflammation and Physical Performance in Patients With NASH
A study testing individual training program in people with Non-alcoholic Fatty Liver Disease, run by Priv.-Doz. Dr. J. Schattenberg at 1 site in Germany.
Trial summary
The aim of the study is to examine the influence of hepatic inflammation or damage on physical performance (maximal oxygen uptake, VO2max) depending on the histologic state of the liver. The study population are patients with fatty liver disease and non-alcoholic steatohepatitis (NASH). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease
- What is being tested?
- individual training program
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteGermany
- Study dates
- Sep 2015to 20 Dec 2017
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- histologically proven NASH or fatty liver disease
Who cannot join
- bariatric surgery within the last 5 years
- BMI< 18,5 kg/m2 or > 45 kg/m2
- heart attack or stroke within the last 6 months
- higher-grade coronary artery disease (CAD III-IV)
- chronic obstructive pulmonary disease (asthma , COPD)
- renal insufficiency
Show all 14Show fewer
- uncontrolled hypertension or metabolic abnormalities
- alcohol consumption > 30 g / day (male) and > 20 g / day (female)
- pregnancy
- concomitant medication able to cause a secondary NASH (eg tamoxifen , corticosteroids )
- concomitant medication able to affect inflammation (eg TNF antagonists)
- concomitant anticoagulant medication (eg phenprocoumon, NOAC)
- other immunological or inflammatory diseases (eg, systemic lupus erythematosus)
- musculoskeletal disorders, preventing sport physiological investigations
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Medical Center of the Johannes Gutenber Univeristy
Mainz, 55131
About this study
Official title: Influence of Hepatic Inflammation and Hepatocellular Apoptosis on Physical Performance and Training Effect in Patients With Non - Alcoholic Steatohepatitis
The aim of the study is to examine the influence of hepatic inflammation or damage on physical performance (maximal oxygen uptake, VO2max) depending on the histologic state of the liver. The study population are patients with fatty liver disease and non-alcoholic steatohepatitis (NASH). All study participants obtain an individual training plan with individual and group training sessions for a period of 8 weeks. At the beginning and end of the training phase a sport physiological examination is carried out. In the study group the effect of regular examinations is surveyed by surrogate parameters of liver inflammation.
Read the detailed description
The study is planned over a period of 24 months. Study participants should be twice examined sport physiologically in a period of 12 weeks. In the study group the influence of regular exercise on surrogate parameters of liver inflammation is investigated over a study period of 8 weeks. Before the exercise all study participants are subjected to a first physiological examination (about 3 hours). This includes a physical examination with detection of body weight, waist circumference and body fat analysis, venous blood, oral glucose tolerance test, ultrasonography of the liver and determination of endothelial function (flow-mediated vasodilatation, FMD) by Doppler analysis. Within 4 weeks after the first examination a sport physical examination is carried out at the Institute of Sports Science at the University of Mainz. This examination contains identification of physical fitness and individual lactate performance diagnostics. In addition, indirect calorimetry is carried out under exercise conditions using spiroergometry to determine the maximal oxygen uptake (VO2max) with special emphasis on the fat metabolism rate at low physical activity. Subsequently to the examination an 8-week training period based on individual training / performance plans is followed. The training plans include independently running exercises for 30-45 minutes two to three times a week. Every two weeks group training sessions are offered accompanied by a sports physician. Within the planed four groups training sessions blood samples will be taken to determinate free circulating DNA and assess lactate values under exercise conditions. After the training phase, a second sport physical examination including physical performance and a final physiological examination including surrogate parameters of liver inflammation are carried out. For statistical analysis, the physical performance of the study participants is examined. Hence patients with histologically proven NASH (NAS score) and confirmed inflammation (increased M30 antigen) are compared to age and gender matched patients with histologically proven fatty liver without inflammation reaction as well as to retrospective data of healthy subjects.
- Conditions
- Non-alcoholic Fatty Liver Disease
- Being tested
- individual training program
- Keywords
- NASH, fatty Liver, VO2 max, M30 antigen
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
individual training programOther
Training period of 8 weeks: Independently running exercises for 30-45 minutes two to three times a week. Every two weeks group training sessions are offered accompanied by a sports physician.
| Study group | Role | What they receive |
|---|---|---|
| individual training program | Experimental | Patients will be offered an individual training program. Physical performance and surrogate parameters of liver inflammation will assessed in physical examinations before and after the training phase. Receives: Other: individual training program |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in physical performance
Change of Vo2max from week 0 to week 8
Measured: 0-8 weeks
Secondary outcomes (1)
Change in liver inflammation
Change of NAS score at week 0 and week 8
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2015 (estimated)
- Study startSep 2015
- Primary completion20 Dec 2017
- Study completion20 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)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
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Priv.-Doz. Dr. J. Schattenberg
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Priv.-Doz. Dr. J. Schattenberg, Johannes Gutenberg University Mainz
- Investigators
- Peter R Galle, MD, Study director, I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02526732
- Sponsor's protocol ID
- 2015_04_001_HELP
- Acronym
- HELP
- Status last verified
- Sep 2018
- First submitted
- 17 Aug 2015
- Last updated
- 5 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Publication in scientific journals and conferences
Publications
Clark JM. The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroenterol. 2006 Mar;40 Suppl 1:S5-10. doi: 10.1097/01.mcg.0000168638.84840.ff.
PubMed 16540768Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013 Mar;58(3):593-608. doi: 10.1016/j.jhep.2012.12.005.
PubMed 23419824Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011 Aug;34(3):274-85. doi: 10.1111/j.1365-2036.2011.04724.x. Epub 2011 May 30.
PubMed 21623852Sanyal AJ. NASH: A global health problem. Hepatol Res. 2011 Jul;41(7):670-4. doi: 10.1111/j.1872-034X.2011.00824.x.
PubMed 21711426Mehal WZ. The Gordian Knot of dysbiosis, obesity and NAFLD. Nat Rev Gastroenterol Hepatol. 2013 Nov;10(11):637-44. doi: 10.1038/nrgastro.2013.146. Epub 2013 Aug 20.
PubMed 23958600Schattenberg JM, Schuppan D. Nonalcoholic steatohepatitis: the therapeutic challenge of a global epidemic. Curr Opin Lipidol. 2011 Dec;22(6):479-88. doi: 10.1097/MOL.0b013e32834c7cfc.
PubMed 22002020Fargion S, Porzio M, Fracanzani AL. Nonalcoholic fatty liver disease and vascular disease: state-of-the-art. World J Gastroenterol. 2014 Oct 7;20(37):13306-24. doi: 10.3748/wjg.v20.i37.13306.
PubMed 25309067Krasnoff JB, Painter PL, Wallace JP, Bass NM, Merriman RB. Health-related fitness and physical activity in patients with nonalcoholic fatty liver disease. Hepatology. 2008 Apr;47(4):1158-66. doi: 10.1002/hep.22137.
PubMed 18266250Noakes TD. Maximal oxygen uptake: "classical" versus "contemporary" viewpoints: a rebuttal. Med Sci Sports Exerc. 1998 Sep;30(9):1381-98. doi: 10.1097/00005768-199809000-00007.
PubMed 9741607Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012 Jun;55(6):2005-23. doi: 10.1002/hep.25762. No abstract available.
PubMed 22488764Sreenivasa Baba C, Alexander G, Kalyani B, Pandey R, Rastogi S, Pandey A, Choudhuri G. Effect of exercise and dietary modification on serum aminotransferase levels in patients with nonalcoholic steatohepatitis. J Gastroenterol Hepatol. 2006 Jan;21(1 Pt 1):191-8. doi: 10.1111/j.1440-1746.2005.04233.x.
PubMed 16706832Fealy CE, Haus JM, Solomon TP, Pagadala M, Flask CA, McCullough AJ, Kirwan JP. Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease. J Appl Physiol (1985). 2012 Jul;113(1):1-6. doi: 10.1152/japplphysiol.00127.2012. Epub 2012 May 10.
PubMed 22582214Bae JC, Suh S, Park SE, Rhee EJ, Park CY, Oh KW, Park SW, Kim SW, Hur KY, Kim JH, Lee MS, Lee MK, Kim KW, Lee WY. Regular exercise is associated with a reduction in the risk of NAFLD and decreased liver enzymes in individuals with NAFLD independent of obesity in Korean adults. PLoS One. 2012;7(10):e46819. doi: 10.1371/journal.pone.0046819. Epub 2012 Oct 22.
PubMed 23110056Kistler KD, Brunt EM, Clark JM, Diehl AM, Sallis JF, Schwimmer JB; NASH CRN Research Group. Physical activity recommendations, exercise intensity, and histological severity of nonalcoholic fatty liver disease. Am J Gastroenterol. 2011 Mar;106(3):460-8; quiz 469. doi: 10.1038/ajg.2010.488. Epub 2011 Jan 4.
PubMed 21206486Swain MG. Fatigue in liver disease: pathophysiology and clinical management. Can J Gastroenterol. 2006 Mar;20(3):181-8. doi: 10.1155/2006/624832.
PubMed 16550262
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Hepatic Inflammation and Hepatocellular Apoptosis on Physical Performance and Training Effect in Patients With Non - Alcoholic Steatohepatitis
- ClinicalTrials.gov ID
- NCT02526732
- Acronym / sponsor ID
- HELP / 2015_04_001_HELP
- Conditions
- Non-alcoholic Fatty Liver Disease
- Keywords
- NASH, fatty Liver, VO2 max, M30 antigen
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Priv.-Doz. Dr. J. SchattenbergUniversity, hospital or other
- Study start
- Sep 2015
- Primary completion
- 20 Dec 2017 (actual)
- Study completion
- 20 Dec 2017 (actual)
- First posted
- 18 Aug 2015 (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.
The aim of the study is to examine the influence of hepatic inflammation or damage on physical performance (maximal oxygen uptake, VO2max) depending on the histologic state of the liver. The study population are patients with fatty liver disease and non-alcoholic steatohepatitis (NASH). All study participants obtain an individual training plan with individual and group training sessions for a period of 8 weeks. At the beginning and end of the training phase a sport physiological examination is carried out. In the study group the effect of regular examinations is surveyed by surrogate parameters of liver inflammation.
Detailed description
The study is planned over a period of 24 months. Study participants should be twice examined sport physiologically in a period of 12 weeks. In the study group the influence of regular exercise on surrogate parameters of liver inflammation is investigated over a study period of 8 weeks. Before the exercise all study participants are subjected to a first physiological examination (about 3 hours). This includes a physical examination with detection of body weight, waist circumference and body fat analysis, venous blood, oral glucose tolerance test, ultrasonography of the liver and determination of endothelial function (flow-mediated vasodilatation, FMD) by Doppler analysis. Within 4 weeks after the first examination a sport physical examination is carried out at the Institute of Sports Science at the University of Mainz. This examination contains identification of physical fitness and individual lactate performance diagnostics. In addition, indirect calorimetry is carried out under exercise conditions using spiroergometry to determine the maximal oxygen uptake (VO2max) with special emphasis on the fat metabolism rate at low physical activity. Subsequently to the examination an 8-week training period based on individual training / performance plans is followed. The training plans include independently running exercises for 30-45 minutes two to three times a week. Every two weeks group training sessions are offered accompanied by a sports physician. Within the planed four groups training sessions blood samples will be taken to determinate free circulating DNA and assess lactate values under exercise conditions. After the training phase, a second sport physical examination including physical performance and a final physiological examination including surrogate parameters of liver inflammation are carried out. For statistical analysis, the physical performance of the study participants is examined. Hence patients with histologically proven NASH (NAS score) and confirmed inflammation (increased M30 antigen) are compared to age and gender matched patients with histologically proven fatty liver without inflammation reaction as well as to retrospective data of healthy subjects.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| individual training program | Experimental | Other: individual training programPatients will be offered an individual training program. Physical performance and surrogate parameters of liver inflammation will assessed in physical examinations before and after the training phase. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- histologically proven NASH or fatty liver disease
Key exclusion criteria (14 listed)
- bariatric surgery within the last 5 years
- BMI< 18,5 kg/m2 or > 45 kg/m2
- heart attack or stroke within the last 6 months
- higher-grade coronary artery disease (CAD III-IV)
- chronic obstructive pulmonary disease (asthma , COPD)
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 |
|---|---|---|
| individual training programTraining period of 8 weeks: Independently running exercises for 30-45 minutes two to three times a week. Every two weeks group training sessions are offered accompanied by a sports physician. | Other | individual training program |
Primary outcome
Change in physical performance
Time frame: 0-8 weeks
Change of Vo2max from week 0 to week 8
1 secondary outcome
Change in liver inflammation
Time frame: 8 weeks
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 5 Sep 2018.
- Background: PubMed 16540768Clark JM. The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroenterol. 2006 Mar;40 Suppl 1:S5-10. doi: 10.1097/01.mcg.0000168638.84840.ff.
- Background: PubMed 23419824Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013 Mar;58(3):593-608. doi: 10.1016/j.jhep.2012.12.005.
- Background: PubMed 21623852Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011 Aug;34(3):274-85. doi: 10.1111/j.1365-2036.2011.04724.x. Epub 2011 May 30.
- Background: PubMed 21711426Sanyal AJ. NASH: A global health problem. Hepatol Res. 2011 Jul;41(7):670-4. doi: 10.1111/j.1872-034X.2011.00824.x.
- Background: PubMed 23958600Mehal WZ. The Gordian Knot of dysbiosis, obesity and NAFLD. Nat Rev Gastroenterol Hepatol. 2013 Nov;10(11):637-44. doi: 10.1038/nrgastro.2013.146. Epub 2013 Aug 20.
- Background: PubMed 22002020Schattenberg JM, Schuppan D. Nonalcoholic steatohepatitis: the therapeutic challenge of a global epidemic. Curr Opin Lipidol. 2011 Dec;22(6):479-88. doi: 10.1097/MOL.0b013e32834c7cfc.
- Background: PubMed 25309067Fargion S, Porzio M, Fracanzani AL. Nonalcoholic fatty liver disease and vascular disease: state-of-the-art. World J Gastroenterol. 2014 Oct 7;20(37):13306-24. doi: 10.3748/wjg.v20.i37.13306.
- Background: PubMed 18266250Krasnoff JB, Painter PL, Wallace JP, Bass NM, Merriman RB. Health-related fitness and physical activity in patients with nonalcoholic fatty liver disease. Hepatology. 2008 Apr;47(4):1158-66. doi: 10.1002/hep.22137.
- Background: PubMed 9741607Noakes TD. Maximal oxygen uptake: "classical" versus "contemporary" viewpoints: a rebuttal. Med Sci Sports Exerc. 1998 Sep;30(9):1381-98. doi: 10.1097/00005768-199809000-00007.
- Background: PubMed 22488764Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012 Jun;55(6):2005-23. doi: 10.1002/hep.25762. No abstract available.
- Background: PubMed 16706832Sreenivasa Baba C, Alexander G, Kalyani B, Pandey R, Rastogi S, Pandey A, Choudhuri G. Effect of exercise and dietary modification on serum aminotransferase levels in patients with nonalcoholic steatohepatitis. J Gastroenterol Hepatol. 2006 Jan;21(1 Pt 1):191-8. doi: 10.1111/j.1440-1746.2005.04233.x.
- Background: PubMed 22582214Fealy CE, Haus JM, Solomon TP, Pagadala M, Flask CA, McCullough AJ, Kirwan JP. Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease. J Appl Physiol (1985). 2012 Jul;113(1):1-6. doi: 10.1152/japplphysiol.00127.2012. Epub 2012 May 10.
- Individual participant dataSharing planned: Yes. Publication in scientific journals and conferences
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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.
Peter R Galle, MD study director
I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing individual training program in people with Non-alcoholic Fatty Liver Disease, run by Priv.-Doz. Dr. J. Schattenberg at 1 site in Germany.
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 1 inclusion and 14 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 5 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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?
Change in physical performance (time frame: 0-8 weeks). 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 NCT02526732, which also lists 22 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 5 Sep 2018.