Microbiome and Sarcopenia in Patients With Liver Cirrhosis
Primary Purpose
Sarcopenia, Liver Cirrhosis
Status
Recruiting
Phase
Not Applicable
Locations
Austria
Study Type
Interventional
Intervention
Fresubin energy
Sponsored by
About this trial
This is an interventional basic science trial for Sarcopenia focused on measuring Liver cirrhosis, Sarcopenia, Microbiome
Eligibility 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
Sites / Locations
- Medical University GrazRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Cirrhosis + sarcopenia
Control
Arm Description
Patients with cirrhosis will receive 200ml of an oral nutritional supplement daily for 7 days.
Patients with sarcopenia and no evidence of cirrhosis and healthy controls
Outcomes
Primary Outcome Measures
Alpha diversity
16s rDNA sequencing of the stool microbiome
Secondary Outcome Measures
Zonulin
ELISA
diamino-oxidase
ELISA
Calprotectin
ELISA
Gut permeability
marker panel
taxonomic composition of the microbiome
16s rDNA sequencing of the stool microbiome
taxonomic composition of the microbiome
16s rDNA sequencing of the stool microbiome
lipopolysaccharide
HEK blue cell assay
sCD14
ELISA
lipopolysaccharide binding protein
ELISA
bacterial DNA
HEK blue cell assay
bacterial translocation
marker panel
cytokine panel
Bead array
carboxylated proteins
ELISA
advanced oxidation end products
ELISA
inflammation
marker panel
myostatin
ELISA
fibroblast growth factor 21
ELISA
insulin like growth factor 1
ELISA
Irisin
ELISA
nutritional status
Questionnaire
Sarcopenia
MR/CT scan
face portrait
face portraits "selfies" will be obtained and AI algorithms will be used to diagnose sarcopenia from selfies
Full Information
NCT ID
NCT03080129
First Posted
March 1, 2017
Last Updated
August 2, 2023
Sponsor
Medical University of Graz
1. Study Identification
Unique Protocol Identification Number
NCT03080129
Brief Title
Microbiome and Sarcopenia in Patients With Liver Cirrhosis
Official Title
Microbiome and Sarcopenia in Patients With Liver Cirrhosis: A Prospective Controlled Cohort Study
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 11, 2017 (Actual)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
December 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of Graz
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
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. Sarcopenia can be diagnosed from patients portraits.
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
whether artificial intelligence can be used to diagnose sarcopenia from face portraits.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcopenia, Liver Cirrhosis
Keywords
Liver cirrhosis, Sarcopenia, Microbiome
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Non-Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cirrhosis + sarcopenia
Arm Type
Experimental
Arm Description
Patients with cirrhosis will receive 200ml of an oral nutritional supplement daily for 7 days.
Arm Title
Control
Arm Type
No Intervention
Arm Description
Patients with sarcopenia and no evidence of cirrhosis and healthy controls
Intervention Type
Dietary Supplement
Intervention Name(s)
Fresubin energy
Intervention Description
dietary protein energy supplement
Primary Outcome Measure Information:
Title
Alpha diversity
Description
16s rDNA sequencing of the stool microbiome
Time Frame
day 1
Secondary Outcome Measure Information:
Title
Zonulin
Description
ELISA
Time Frame
day 1
Title
diamino-oxidase
Description
ELISA
Time Frame
day 1, day 7
Title
Calprotectin
Description
ELISA
Time Frame
day 1
Title
Gut permeability
Description
marker panel
Time Frame
change between day 1 and day 7
Title
taxonomic composition of the microbiome
Description
16s rDNA sequencing of the stool microbiome
Time Frame
day 1
Title
taxonomic composition of the microbiome
Description
16s rDNA sequencing of the stool microbiome
Time Frame
change between day 1 and day 7
Title
lipopolysaccharide
Description
HEK blue cell assay
Time Frame
day 1
Title
sCD14
Description
ELISA
Time Frame
day 1
Title
lipopolysaccharide binding protein
Description
ELISA
Time Frame
day 1
Title
bacterial DNA
Description
HEK blue cell assay
Time Frame
day 1
Title
bacterial translocation
Description
marker panel
Time Frame
change between day 1 and day 7
Title
cytokine panel
Description
Bead array
Time Frame
day 1
Title
carboxylated proteins
Description
ELISA
Time Frame
day 1
Title
advanced oxidation end products
Description
ELISA
Time Frame
day 1
Title
inflammation
Description
marker panel
Time Frame
change between day 1 and day 7
Title
myostatin
Description
ELISA
Time Frame
day 1
Title
fibroblast growth factor 21
Description
ELISA
Time Frame
day 1
Title
insulin like growth factor 1
Description
ELISA
Time Frame
day 1
Title
Irisin
Description
ELISA
Time Frame
day 1
Title
nutritional status
Description
Questionnaire
Time Frame
day 1
Title
Sarcopenia
Description
MR/CT scan
Time Frame
day 1
Title
face portrait
Description
face portraits "selfies" will be obtained and AI algorithms will be used to diagnose sarcopenia from selfies
Time Frame
day 1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vanessa Stadlbauer-Köllner, AssocProf Dr
Phone
+4331638582282
Email
vanessa.stadlbauer@medunigraz.at
First Name & Middle Initial & Last Name or Official Title & Degree
Julia Haberl, BSc
Phone
+4331638580777
Email
julia.haberl@klinikum-graz.at
Facility Information:
Facility Name
Medical University Graz
City
Graz
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vanessa Stadlbauer-Köllner, MD
Phone
0043 316 385
Ext
82282
Email
vanessa.stadlbauer@medunigraz.at
12. IPD Sharing Statement
Plan to Share IPD
No
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Microbiome and Sarcopenia in Patients With Liver Cirrhosis
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