Effect of L-ornithine-L-aspertate (LOLA) on the Gut Microbiome

Study Overview
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Brief Summary
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Study to test the effect of the drug L-ornithine.L-aspertate (LOLA) on microorganisms in the digestive tract in patients with liver cirrhosis (damage of the liver due to liver disease)

Detailed Description
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Liver cirrhosis is associated with gut microbiome dysbiosis, which may drive intestinal inflammation, gut barrier dysfunction and the development of complications. LOLA is a well-established drug against elevated ammonia levels that contribute to hepatic encephalopathy and sarcopenia. In a recent retrospective study, LOLA has been shown to improve gut microbiome dysbiosis. In this study we aim to investigate whether LOLA therapy over three months in patients with liver cirrhosis (irrespective of the etiology) and covert or overt hepatic encephalopathy (HE) leads to an improvement in gut microbiome dysbiosis, as well as markers of gut permeability, inflammation, muscle function and ammonia levels.

Official Title
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An Observational Study on the Effect of L-ornithine-L-aspertate (LOLA) on the Flavonifractor Abundance in the Gut Microbiome in Liver Cirrhosis

Conditions
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Cirrhosis

Intervention / Treatment
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* Drug: L-ornithine L-aspartate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Liver cirrhosis (clinical/radiological/histological diagnosis) Indication for LOLA use (covert or over hepatic encephalopathy, Grad 0-2)) Written informed consent Age 18 -100 years Exclusion Criteria: • Allergy to LOLA or its constituents, or to medications with a similar chemical structure (oral nutritional supplements are allowed when stable >/= 8 weeks before and during the study) Recent (</= 8 weeks) changes of the dose of the lactulose therapy for hepatic encephalopathy Rifaximin or any other antibiotic therapy within the past 4 weeks Intake of LOLA in the past four weeks before inclusion Intake of L-dopamine Renal insufficiency with a serum creatinine >3mg/dl Hepatocellular carcinoma BCLC D under best supportive care Inability to give informed consent Pregnancy or breastfeeding Participation in another interventional trial within the last 30 days

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-ornithine-L-aspertate<br>L-ornithine-L-aspertate 18g per day | Drug: L-ornithine L-aspartate<br>* Amino acid combination<br>* Other names: Hepa-Merz;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiome | Increase of the genus Flavonifractor in the gut microbiome after 3 months of LOLA treatment | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alpha diversity | Change in alpha diversity of the gut microbiome after 3 months of LOLA treatment | 3 months | 
| Beta diversity | Change in beta diversity of the gut microbiome after 3 months of LOLA treatment | 3 months | 
| Taxonomic composition | Change in taxonomic composition (beyond Flavonifractor) of the gut microbiome after 3 months of LOLA treatment | 3 months | 
| Predicted metagenomics | Change in predicted gut microbiome function after 3 months of LOLA treatment | 3 months | 
| Metabolomics | Change in stool, serum or urine metabolite composition after 3 months of LOLA treatment | 3 months | 
| Gut permeability | Change in biomarkers of gut permeability (zonulin, DAO, sCD14, LBP) after 3 months of LOLA treatment | 3 months | 
| Handgrip strength | Change in handgrip strength after 3 months of LOLA treatment | 3 months | 
| Muscle function | Change in gait speed and balance after 3 months of LOLA treatment | 3 months | 
| Ammonia in serum | Change in ammonia blood levels after 3 months of LOLA treatment | 3 months | 
| Mid-arm circumference and triceps fold thickness | Change in anthropometric parameters (Mid-arm circumference and triceps fold thickness) after 3 months of LOLA treatment | 3 months | 
| short form (SF)-36 | Change in quality of life after 3 months of LOLA treatment, 8 domains, 0-100 points, higher points indicate higher quality of life | 3 months |