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

Cirrhosis Clinical Trial

— LOLAbiome  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05737030
• Other study ID #: LOLAbiome
• Secondary ID: 2022-002924-11
• Status: Recruiting
• Phase: Phase 4
• Start date: February 6, 2023
• Est. completion date: December 2025

Study information

• Verified date: March 2024
• Source: Medical University of Graz
• Contact: Angela Horvath
• Phone: 0043 316 385
• Email: angela.horvath[@]cbmed.at
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 55
• Est. completion date: December 2025
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cirrhosis
• Fibrosis
• Liver Cirrhosis

Intervention

Drug:
• L-ornithine L-aspartate
Amino acid combination

Locations

Country	Name	City	State
Austria	Department of Internal Medicine, Medical University of Graz	Graz

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of Graz	CBmed Ges.m.b.H.

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Microbiome	Increase of the genus Flavonifractor in the gut microbiome after 3 months of LOLA treatment	3 months
Secondary	Alpha diversity	Change in alpha diversity of the gut microbiome after 3 months of LOLA treatment	3 months
Secondary	Beta diversity	Change in beta diversity of the gut microbiome after 3 months of LOLA treatment	3 months
Secondary	Taxonomic composition	Change in taxonomic composition (beyond Flavonifractor) of the gut microbiome after 3 months of LOLA treatment	3 months
Secondary	Predicted metagenomics	Change in predicted gut microbiome function after 3 months of LOLA treatment	3 months
Secondary	Metabolomics	Change in stool, serum or urine metabolite composition after 3 months of LOLA treatment	3 months
Secondary	Gut permeability	Change in biomarkers of gut permeability (zonulin, DAO, sCD14, LBP) after 3 months of LOLA treatment	3 months
Secondary	Handgrip strength	Change in handgrip strength after 3 months of LOLA treatment	3 months
Secondary	Muscle function	Change in gait speed and balance after 3 months of LOLA treatment	3 months
Secondary	Ammonia in serum	Change in ammonia blood levels after 3 months of LOLA treatment	3 months
Secondary	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
Secondary	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