Hepatic Inflammation and Physical Performance in Patients With NASH

NCT02526732 | Completed

• 1 other identifier: 2015_04_001_HELP
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Non-alcoholic Fatty Liver Disease

Keywords

NASH; fatty Liver; VO2 max; M30 antigen

Outcome Measures

Primary Outcomes (1)

• Change in physical performance

  Change of Vo2max from week 0 to week 8

  0-8 weeks

Secondary Outcomes (1)

• Change in liver inflammation

  8 weeks

Study Arms (1)

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.

Other: individual training program

Interventions

individual training program OTHER

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.

individual training program

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• histologically proven NASH or fatty liver disease

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Priv.-Doz. Dr. J. Schattenberg: lead

Study Sites (1)

University Medical Center of the Johannes Gutenber Univeristy

Mainz, 55131, Germany

Location

Related Publications (22)

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  PMID: 16540768 BACKGROUND

• Blachier 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.

  PMID: 23419824 BACKGROUND

• Vernon 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.

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• Sanyal AJ. NASH: A global health problem. Hepatol Res. 2011 Jul;41(7):670-4. doi: 10.1111/j.1872-034X.2011.00824.x.

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• Mehal 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.

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• Schattenberg 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.

  PMID: 22002020 BACKGROUND

• Fargion 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.

  PMID: 25309067 BACKGROUND

• Krasnoff 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.

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  PMID: 9741607 BACKGROUND

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  PMID: 22488764 BACKGROUND

• Sreenivasa 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.

  PMID: 16706832 BACKGROUND

• Fealy 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.

  PMID: 22582214 BACKGROUND

• Bae 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.

  PMID: 23110056 BACKGROUND

• Kistler 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.

  PMID: 21206486 BACKGROUND

• Swain MG. Fatigue in liver disease: pathophysiology and clinical management. Can J Gastroenterol. 2006 Mar;20(3):181-8. doi: 10.1155/2006/624832.

  PMID: 16550262 BACKGROUND

• Brun P, Castagliuolo I, Di Leo V, Buda A, Pinzani M, Palu G, Martines D. Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 2007 Feb;292(2):G518-25. doi: 10.1152/ajpgi.00024.2006. Epub 2006 Oct 5.

  PMID: 17023554 BACKGROUND

• Wigg AJ, Roberts-Thomson IC, Dymock RB, McCarthy PJ, Grose RH, Cummins AG. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis. Gut. 2001 Feb;48(2):206-11. doi: 10.1136/gut.48.2.206.

  PMID: 11156641 BACKGROUND

• Miura K, Ohnishi H. Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease. World J Gastroenterol. 2014 Jun 21;20(23):7381-91. doi: 10.3748/wjg.v20.i23.7381.

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• Zhu L, Baker SS, Gill C, Liu W, Alkhouri R, Baker RD, Gill SR. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology. 2013 Feb;57(2):601-9. doi: 10.1002/hep.26093. Epub 2013 Jan 8.

  PMID: 23055155 BACKGROUND

• Huber Y, Pfirrmann D, Gebhardt I, Labenz C, Gehrke N, Straub BK, Ruckes C, Bantel H, Belda E, Clement K, Leeming DJ, Karsdal MA, Galle PR, Simon P, Schattenberg JM. Improvement of non-invasive markers of NAFLD from an individualised, web-based exercise program. Aliment Pharmacol Ther. 2019 Oct;50(8):930-939. doi: 10.1111/apt.15427. Epub 2019 Jul 25.

  PMID: 31342533 DERIVED

• Pfirrmann D, Huber Y, Schattenberg JM, Simon P. Web-Based Exercise as an Effective Complementary Treatment for Patients With Nonalcoholic Fatty Liver Disease: Intervention Study. J Med Internet Res. 2019 Jan 2;21(1):e11250. doi: 10.2196/11250.

  PMID: 30602434 DERIVED

• Pfirrmann D, Haller N, Huber Y, Jung P, Lieb K, Gockel I, Poplawska K, Schattenberg JM, Simon P. Applicability of a Web-Based, Individualized Exercise Intervention in Patients With Liver Disease, Cystic Fibrosis, Esophageal Cancer, and Psychiatric Disorders: Process Evaluation of 4 Ongoing Clinical Trials. JMIR Res Protoc. 2018 May 22;7(5):e106. doi: 10.2196/resprot.8607.

  PMID: 29789277 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fatty Liver

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Study Officials

• Peter R Galle, MD

  I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prov.-Doz. Dr. med.

Study Record Dates

• First Submitted: August 17, 2015
• First Posted: August 18, 2015
• Study Start: September 1, 2015
• Primary Completion: December 20, 2017
• Study Completion: December 20, 2017
• Last Updated: September 5, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)