Clinical trial NCT05737030: Effect of L-ornithine-L-aspertate (LOLA) on the Gut Microbiome
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Cirrhosis
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
Collaborators: name: CBmed Ges.m.b.H.
First posted: 2023-02-21
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Microbiome
timeFrame: 3 months
Secondary outcomes:
measure: Alpha diversity
timeFrame: 3 months
measure: Beta diversity
timeFrame: 3 months
measure: Taxonomic composition
timeFrame: 3 months
measure: Predicted metagenomics
timeFrame: 3 months
measure: Metabolomics
timeFrame: 3 months
measure: Gut permeability
timeFrame: 3 months
measure: Handgrip strength
timeFrame: 3 months
measure: Muscle function
timeFrame: 3 months
measure: Ammonia in serum
timeFrame: 3 months
measure: Mid-arm circumference and triceps fold thickness
timeFrame: 3 months
measure: short form (SF)-36
timeFrame: 3 months
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Department of Internal Medicine, Medical University of Graz
Study officials:
References: