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

• Sponsor: Medical University of Graz (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05737030
• Collaborator: CBmed Ges.m.b.H. (Other)
• Enrollment: 55
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 22.8
• Patients Per Site Per Month: 2.4

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Cirrhosis	Drug: L-ornithine L-aspartate	Phase 4

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 55 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Feb 6, 2023
• Anticipated Primary Completion Date: Feb 1, 2024
• Anticipated Study Completion Date: Jan 1, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Microbiome [3 months]

   Increase of the genus Flavonifractor in the gut microbiome after 3 months of LOLA treatment

Secondary Outcome Measures

1. Alpha diversity [3 months]

   Change in alpha diversity of the gut microbiome after 3 months of LOLA treatment

2. Beta diversity [3 months]

   Change in beta diversity of the gut microbiome after 3 months of LOLA treatment

3. Taxonomic composition [3 months]

   Change in taxonomic composition (beyond Flavonifractor) of the gut microbiome after 3 months of LOLA treatment

4. Predicted metagenomics [3 months]

   Change in predicted gut microbiome function after 3 months of LOLA treatment

5. Metabolomics [3 months]

   Change in stool, serum or urine metabolite composition after 3 months of LOLA treatment

6. Gut permeability [3 months]

   Change in biomarkers of gut permeability (zonulin, DAO, sCD14, LBP) after 3 months of LOLA treatment

7. Handgrip strength [3 months]

   Change in handgrip strength after 3 months of LOLA treatment

8. Muscle function [3 months]

   Change in gait speed and balance after 3 months of LOLA treatment

9. Ammonia in serum [3 months]

   Change in ammonia blood levels after 3 months of LOLA treatment

10. 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

11. SF36 [3 months]

    Change in quality of life after 3 months of LOLA treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Internal Medicine, Medical University of Graz	Graz		Austria	8010

Sponsors and Collaborators

• Medical University of Graz
• CBmed Ges.m.b.H.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Vanessa Stadlbauer-Koellner, MD, Assoc. Prof., Medical University of Graz
• ClinicalTrials.gov Identifier: NCT05737030
• Other Study ID Numbers: LOLAbiome; 2022-002924-11
• First Posted: Feb 21, 2023
• Last Update Posted: Feb 21, 2023
• Last Verified: Feb 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Liver Cirrhosis; Fibrosis; N-Methylaspartate

Study Results

No Results Posted as of Feb 21, 2023