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

Primary Purpose

Cirrhosis

Status
Recruiting
Phase
Phase 4
Locations
Austria
Study Type
Interventional
Intervention
L-ornithine L-aspartate
Sponsored by
Medical University of Graz
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cirrhosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Internal Medicine, Medical University of GrazRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

L-ornithine-L-aspertate

Arm Description

L-ornithine-L-aspertate 18g per day

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Alpha diversity
Change in alpha diversity of the gut microbiome after 3 months of LOLA treatment
Beta diversity
Change in beta diversity of the gut microbiome after 3 months of LOLA treatment
Taxonomic composition
Change in taxonomic composition (beyond Flavonifractor) of the gut microbiome after 3 months of LOLA treatment
Predicted metagenomics
Change in predicted gut microbiome function after 3 months of LOLA treatment
Metabolomics
Change in stool, serum or urine metabolite composition after 3 months of LOLA treatment
Gut permeability
Change in biomarkers of gut permeability (zonulin, DAO, sCD14, LBP) after 3 months of LOLA treatment
Handgrip strength
Change in handgrip strength after 3 months of LOLA treatment
Muscle function
Change in gait speed and balance after 3 months of LOLA treatment
Ammonia in serum
Change in ammonia blood levels after 3 months of LOLA treatment
Mid-arm circumference and triceps fold thickness
Change in anthropometric parameters (Mid-arm circumference and triceps fold thickness) after 3 months of LOLA treatment
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

Full Information

First Posted
February 12, 2023
Last Updated
March 25, 2023
Sponsor
Medical University of Graz
Collaborators
CBmed Ges.m.b.H.
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1. Study Identification

Unique Protocol Identification Number
NCT05737030
Brief Title
Effect of L-ornithine-L-aspertate (LOLA) on the Gut Microbiome
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 6, 2023 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of Graz
Collaborators
CBmed Ges.m.b.H.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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)
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cirrhosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
55 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
L-ornithine-L-aspertate
Arm Type
Experimental
Arm Description
L-ornithine-L-aspertate 18g per day
Intervention Type
Drug
Intervention Name(s)
L-ornithine L-aspartate
Other Intervention Name(s)
Hepa-Merz
Intervention Description
Amino acid combination
Primary Outcome Measure Information:
Title
Microbiome
Description
Increase of the genus Flavonifractor in the gut microbiome after 3 months of LOLA treatment
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Alpha diversity
Description
Change in alpha diversity of the gut microbiome after 3 months of LOLA treatment
Time Frame
3 months
Title
Beta diversity
Description
Change in beta diversity of the gut microbiome after 3 months of LOLA treatment
Time Frame
3 months
Title
Taxonomic composition
Description
Change in taxonomic composition (beyond Flavonifractor) of the gut microbiome after 3 months of LOLA treatment
Time Frame
3 months
Title
Predicted metagenomics
Description
Change in predicted gut microbiome function after 3 months of LOLA treatment
Time Frame
3 months
Title
Metabolomics
Description
Change in stool, serum or urine metabolite composition after 3 months of LOLA treatment
Time Frame
3 months
Title
Gut permeability
Description
Change in biomarkers of gut permeability (zonulin, DAO, sCD14, LBP) after 3 months of LOLA treatment
Time Frame
3 months
Title
Handgrip strength
Description
Change in handgrip strength after 3 months of LOLA treatment
Time Frame
3 months
Title
Muscle function
Description
Change in gait speed and balance after 3 months of LOLA treatment
Time Frame
3 months
Title
Ammonia in serum
Description
Change in ammonia blood levels after 3 months of LOLA treatment
Time Frame
3 months
Title
Mid-arm circumference and triceps fold thickness
Description
Change in anthropometric parameters (Mid-arm circumference and triceps fold thickness) after 3 months of LOLA treatment
Time Frame
3 months
Title
short form (SF)-36
Description
Change in quality of life after 3 months of LOLA treatment, 8 domains, 0-100 points, higher points indicate higher quality of life
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Angela Horvath
Phone
0043 316 385
Ext
28805
Email
angela.horvath@cbmed.at
Facility Information:
Facility Name
Department of Internal Medicine, Medical University of Graz
City
Graz
ZIP/Postal Code
8010
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vanessa Stadlbauer, MD
Phone
0043316385
Ext
82282
Email
vanessa.stadlbauer@medunigraz.at

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

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

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