Profermin®: Prevention of Progression in Alcoholic Liver Disease by Modulating Dysbiotic Microbiota

NCT ID: NCT03863730

Last Updated: 2023-11-07

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-01
• Study Completion Date: 2031-02-28

Brief Summary

Investigators wishes to influence the gut microbiota in patients with alcoholic liver disease in a randomized controlled clinical trial. The investigators hypothesize that the alcohol-related dysbiosis seen in these patients can be changed and disease progression haltered by modulating microbiota with probiotics during 24 weeks.

Detailed Description

Chronic alcohol overuse is associated with increased gut permeability and in addition, the intestinal microbiota changes qualitatively (dysbiosis) and quantitatively (bacterial overgrowth) in alcoholic liver disease in favour of a microbiota with increased invasive potential. As a consequence, an increased load of bacterial products is transported to the liver leading to inflammation and fibrogenesis.

This cross talk between the intestinal microbiota and the liver constitute a gut-liver axis, which is increasingly recognized as key mechanism in the progression of liver disease and pathogenesis of liver related complications.

The investigators hypothesize that the gut microbiota and its metabolites are major drivers of fibrosis in human liver disease and that modulating the intestinal flora by Profermin® (a food for special medical purposes) will modulate the alcohol related dysbiotic signatures in the microbiota which may halter disease progression by reducing activity of hepatic stellate cells.

Dietary supplements that alter the microbiome towards a more beneficent type may improve liver inflammation and thus be a better alternative than supplements that simply add nutrients. Investigators expect that the trial will provide proof-of-concept for a sustainable dietary strategy in liver fibrosis.

Examples of biopsies which did not meet quality criteria for reliable histological reading, led to inclusion of 16 extra patients. In total we included 56 patients to ensure an adequate number of participants with valid liver biopsy data for assessment of the primary endpoint and intention-to-treat analysis.

Conditions

Alcoholic Liver Disease; Liver Cirrhosis, Alcoholic; Probiotics; Liver Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Profermin Plus®

Intervention group will be drinking the liver-specialized product Profermin Plus®, based on fermented oats, Lactobacillus Plantarum 299v, barley malt and lecithin. The product also contains Thiamin, which is beneficial in patients with liver diseases.

Group Type: EXPERIMENTAL

Profermin Plus, FSMP, probiotics

Intervention Type: DIETARY_SUPPLEMENT

Participants will have to supply their normal intake with Profermin Plus, FSMP, Prbiotics product twice every day for 24 weeks.

The product Profermin Plus® has changed its name to ReFerm®. The content of the product is unchanged. The change occurred after the clinical part of the study was completed.

Fresubin®

Fresubin® is a standard FSMP and will be used as control product. Since Profermin Plus® is a disease-specific FSMP, the documentation must prove an effect that cannot be achieved by modification of the normal diet alone or by standard FSMP's. Therefor the comparator must be a standard FSMP, i.e. a nutritionally complete FSMP with standard nutrient formulation, which may constitute the sole source of nourishment of a person, hence the reason for using Fresubin® as comparator.

Group Type: ACTIVE_COMPARATOR

Fresubin, dietary supplement

Intervention Type: DIETARY_SUPPLEMENT

Participants will have to supply their normal intake with the control product, Fresubin, dietary supplement twice every day for 24 weeks.

Interventions

Profermin Plus, FSMP, probiotics

Participants will have to supply their normal intake with Profermin Plus, FSMP, Prbiotics product twice every day for 24 weeks.

The product Profermin Plus® has changed its name to ReFerm®. The content of the product is unchanged. The change occurred after the clinical part of the study was completed.

Intervention Type: DIETARY_SUPPLEMENT

Fresubin, dietary supplement

Participants will have to supply their normal intake with the control product, Fresubin, dietary supplement twice every day for 24 weeks.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Prior or ongoing harmful alcohol intake defined as an average of ≥24g alcohol/day for women and ≥36g/d for men for ≥ 5 year.

• Outpatients with compensated advanced chronic alcohol-related liver disease, defined as stable patients with:

1. liver stiffness ≥15 kPa and asymptomatic and/or

2. New liver biopsy (<6months) with at least F3 fibrosis (kleiner) and/or

3. Liver biopsy older that 6 months with liver stiffness ≥10 kPa

• Understand and speak Danish written and orally
• Informed consent

Exclusion Criteria

• Hospitalised
• Moderete or severe Ascites, determined from imaging diagnostics
• High-risk varices needing interventional treatment (endoscopy, TIPS)
• Child-Pugh C score
• MELD-Na ≥15
• Lactose intolerance
• Coeliac disease
• Irritable bowel syndrome defined by ROME III criteria
• Antibiotic treatment the prior 3 months
• Treatment with nutritional drinks, probiotics or prebiotics within the last 3 months
• The investigator judge that the patient would not be compliant with trial medicine
• Pregnancy
• Known liver disease other than alcoholic, of any aetiology
• Severe malnutrition
• Malignancy - except spino- or basocellular skin cancer. Patients with prior malignant disease are allowed if cancer-free for at least one year
• Recent infectious gastroenteritis (for the last 6 weeks)

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Region of Southern Denmark

OTHER

Sponsor Role: collaborator

Odense Patient Data Explorative Network

OTHER

Sponsor Role: collaborator

University of Southern Denmark

OTHER

Sponsor Role: collaborator

Nordisk Rebalance A/S

INDUSTRY

Sponsor Role: collaborator

Odense University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Aleksander Krag

Professor, PhD, Cand.Med.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

FLASH - Centre of Liver Research

Odense, Fyn, Denmark

Odense University Hospital

Odense, , Denmark

Countries

Denmark

Other Identifiers

S-20170163

Identifier Type: -

Identifier Source: org_study_id