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

Phase 4

Active, not recruiting

• Conditions: Cirrhosis
• Interventions: Drug: L-ornithine L-aspartate

• Registration Number: NCT05737030
• Lead Sponsor: Medical University of Graz

Brief 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)

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 Timeline

• Study Start: 2023-02-06
• Study First Submitted: 2023-02-12
• Study First Submitted QC: 2023-02-12
• Study First Posted: 2023-02-21
• Primary Completion: 2024-07-23
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-06
• Last Update Posted: 2025-02-10
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 55

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
L-ornithine-L-aspertate	L-ornithine L-aspartate	L-ornithine-L-aspertate 18g per day

Primary Outcome Measures

Name	Time	Method
Microbiome	3 months	Increase of the genus Flavonifractor in the gut microbiome after 3 months of LOLA treatment

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Department of Internal Medicine, Medical University of Graz; 🇦🇹 Graz, Austria