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Microbiome and Sarcopenia in Patients With Liver Cirrhosis

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ClinicalTrials.gov Identifier: NCT03080129
Recruitment Status : Recruiting
First Posted : March 15, 2017
Last Update Posted : March 18, 2019
Sponsor:
Information provided by (Responsible Party):
Medical University of Graz

Brief Summary:

Protein-energy malnutrition (PEM) occurs in 65-90% of patients with liver cirrhosis. Severity of malnutrition correlates with progression of liver disease and leads to sarcopenia in 30-70% of cirrhotic patients. Malnutrition and sarcopenia are associated with an increased risk of complications and mortality.

In cirrhosis the gut microbiome is altered leading to increased gut permeability, bacterial translocation and inflammation. Since the microbiome is involved in nutrient uptake and metabolism, it is hypothesized that microbiome alterations contribute to sarcopenia. A prospective controlled cohort study to investigate the interrelation of microbiome changes and sarcopenia in cirrhosis will be conducted. Furthermore the effect of nutritional interventions on the microbiome in cirrhosis will be studied. From this study information on how the gut microbiome composition and sarcopenia are associated in cirrhosis and if modulation of the gut microbiome by nutritional interventions is feasible will be collected.


Condition or disease Intervention/treatment Phase
Sarcopenia Liver Cirrhosis Dietary Supplement: Fresubin energy Not Applicable

Detailed Description:

Scientific background

Protein-energy malnutrition (PEM) occurs in 65-90% of patients with chronic liver disease. PEM is caused by various factors including poor dietary intake, loss of appetite, decreased hepatic protein synthesis, malabsorption and hypermetabolism. It is associated with an increased risk of complications including ascites, hepatic encephalopathy, variceal bleeding, hepatorenal syndrome and mortality. There is a direct relation between the progression of the liver disease and the severity of malnutrition.

Malnutrition and sarcopenia in liver cirrhosis patients

PEM leads to sarcopenia as a common, but frequently overlooked, complication. Sarcopenia is defined as a decrease in muscle mass two standard deviations below the healthy young adult mean. Sarcopenia is associated with aging, chronic diseases and malignancy. To determine the severity of muscle wasting, computed tomography scan (CT) or magnetic resonance imaging (MRI) are an objective and reproducible technique. Sarcopenia negatively impacts on survival, correlates with the risk of infections, increases surgical risk and leads to a poor quality of life. Besides PEM also inflammation is of importance in the development of sarcopenia.

Diversity in the microbiome in patients with liver cirrhosis and association with sarcopenia.

The gut microbiome of liver cirrhosis patients is altered compared to healthy individuals. Dysbiosis leads to an increased gut permeability, bacterial translocation and inflammation. This contributes to fibrogenesis and may also be related to hepatocarcinogenesis. Hence, new treatment approaches in cirrhosis focus on changing the microbial landscape.

Modulation the gut microbiome may also be a strategy to reverse sarcopenia by reducing systematic inflammation.

Hypothesis and aims

There is an association between gut microbiome composition, gut permeability and the existence of sarcopenia in cirrhotic patients.

Primary hypothesis: Diversity of the gut microbiome is reduced in liver cirrhosis patients with sarcopenia compared to those without sarcopenia or healthy controls.

Secondary hypotheses: There is an association between gut microbiome composition, biomarker of gut permeability and bacterial translocation with the presence of sarcopenia in cirrhosis. Oral nutrition supplements (ONS) can influence the composition of the gut microbiome, gut permeability, bacterial translocation and inflammation.

Aims: to investigate:

  • the composition of the gut microbiome
  • biomarkers of gut permeability, bacterial translocation and inflammation
  • the incidence and severity of sarcopenia
  • the impact of oral nutrition supplements (ONS) on the gut microbiome

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: Microbiome and Sarcopenia in Patients With Liver Cirrhosis: A Prospective Controlled Cohort Study
Actual Study Start Date : April 11, 2017
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cirrhosis

Arm Intervention/treatment
Experimental: Cirrhosis + sarcopenia
Patients with cirrhosis will receive 200ml of an oral nutritional supplement daily for 7 days.
Dietary Supplement: Fresubin energy
dietary protein energy supplement

No Intervention: Control
Patients with sarcopenia and no evidence of cirrhosis and healthy controls



Primary Outcome Measures :
  1. Alpha diversity [ Time Frame: day 1 ]
    16s rDNA sequencing of the stool microbiome


Secondary Outcome Measures :
  1. Zonulin [ Time Frame: day 1 ]
    ELISA

  2. diamino-oxidase [ Time Frame: day 1, day 7 ]
    ELISA

  3. Calprotectin [ Time Frame: day 1 ]
    ELISA

  4. Gut permeability [ Time Frame: change between day 1 and day 7 ]
    marker panel

  5. taxonomic composition of the microbiome [ Time Frame: day 1 ]
    16s rDNA sequencing of the stool microbiome

  6. taxonomic composition of the microbiome [ Time Frame: change between day 1 and day 7 ]
    16s rDNA sequencing of the stool microbiome

  7. lipopolysaccharide [ Time Frame: day 1 ]
    HEK blue cell assay

  8. sCD14 [ Time Frame: day 1 ]
    ELISA

  9. lipopolysaccharide binding protein [ Time Frame: day 1 ]
    ELISA

  10. bacterial DNA [ Time Frame: day 1 ]
    HEK blue cell assay

  11. bacterial translocation [ Time Frame: change between day 1 and day 7 ]
    marker panel

  12. cytokine panel [ Time Frame: day 1 ]
    Bead array

  13. carboxylated proteins [ Time Frame: day 1 ]
    ELISA

  14. advanced oxidation end products [ Time Frame: day 1 ]
    ELISA

  15. inflammation [ Time Frame: change between day 1 and day 7 ]
    marker panel

  16. myostatin [ Time Frame: day 1 ]
    ELISA

  17. fibroblast growth factor 21 [ Time Frame: day 1 ]
    ELISA

  18. insulin like growth factor 1 [ Time Frame: day 1 ]
    ELISA

  19. Irisin [ Time Frame: day 1 ]
    ELISA

  20. nutritional status [ Time Frame: day 1 ]
    Questionnaire

  21. Sarcopenia [ Time Frame: day 1 ]
    MR/CT scan

  22. face portrait [ Time Frame: day 1 ]
    face portraits "selfies" will be obtained and AI algorithms will be used to diagnose sarcopenia from selfies



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Hospitalized patients for any reason with clinical/radiological/histological diagnosis of cirrhosis
  • Age >18y
  • Informed consent
  • CT/MRI scan within +/-14 days of the baseline study visit

Exclusion Criteria:

  • Hepatic encephalopathy > grade 2 and or other cognitive disorder not allowing informed consent
  • advanced hepatocellular carcinoma
  • Any other condition or circumstance, which, in the opinion of the investigator, would affect the patient's ability to participate in the protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03080129


Contacts
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Contact: Vanessa Stadlbauer-Köllner, AssocProf Dr +4331638582282 vanessa.stadlbauer@medunigraz.at
Contact: Julia Haberl, BSc +4331638580777 julia.haberl@klinikum-graz.at

Locations
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Austria
Medical University Graz Recruiting
Graz, Austria
Contact: Vanessa Stadlbauer-Köllner, MD    0043 316 385 ext 82282    vanessa.stadlbauer@medunigraz.at   
Sponsors and Collaborators
Medical University of Graz

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Responsible Party: Medical University of Graz
ClinicalTrials.gov Identifier: NCT03080129     History of Changes
Other Study ID Numbers: SAR
First Posted: March 15, 2017    Key Record Dates
Last Update Posted: March 18, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Medical University of Graz:
Liver cirrhosis
Sarcopenia
Microbiome

Additional relevant MeSH terms:
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Liver Cirrhosis
Sarcopenia
Fibrosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Muscular Atrophy
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Atrophy
Pathological Conditions, Anatomical
Signs and Symptoms