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

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

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)

Study Overview

• Status: Recruiting
• Conditions: Cirrhosis
• Intervention / Treatment: Drug: L-ornithine L-aspartate

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 55
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Angela Horvath; Phone Number: 28805 0043 316 385; Email: angela.horvath@cbmed.at

Study Locations

• Austria
  • Graz, Austria, 8010
    • Recruiting
    • Department of Internal Medicine, Medical University of Graz
    • Contact: Vanessa Stadlbauer, MD; Phone Number: 82282 0043316385; Email: vanessa.stadlbauer@medunigraz.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L-ornithine-L-aspertate; L-ornithine-L-aspertate 18g per day	Drug: L-ornithine L-aspartate; Amino acid combination; Other Names: Hepa-Merz

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Collaborators: CBmed Ges.m.b.H.

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2023
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: February 12, 2023
• First Submitted That Met QC Criteria: February 12, 2023
• First Posted (Actual): February 21, 2023

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Agents; Excitatory Amino Acid Agonists; N-Methylaspartate
• Other Study ID Numbers: LOLAbiome; 2022-002924-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Sequencing data will be deposited in an open access repository together with metadata
• IPD Sharing Time Frame: 2023
• IPD Sharing Access Criteria: open access
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No