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

NCT03863730 | Active Not Recruiting

• 1 other identifier: S-20170163
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

Food for special medical purposes; Gut and liver axis

Outcome Measures

Primary Outcomes (1)

• Hepatic stellate cell activity

  Attenuation of liver hepatic stellate cell activity, defined as the proportion of patients with a 10% or more reduction in activated hepatic stellate cells, measured by a-smooth muscle actin (a-SMA) stain quantification of liver biopsies.

  24 weeks

Secondary Outcomes (28)

• Hepatic a-SMA activity

  24 weeks

• Hepatic inflammation

  24 weeks

• Alfa-smooth muscle actin concentration

  24 weeks

• Hepatic venous pressure gradient (HVPG)

  24 weeks

• Reduction in non-invasive fibrosis markers

  24 weeks

Study Arms (2)

Profermin Plus®

EXPERIMENTAL

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.

Dietary Supplement: Profermin Plus, FSMP, probiotics

Fresubin®

ACTIVE COMPARATOR

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.

Dietary Supplement: Fresubin, dietary supplement

Interventions

Profermin Plus, FSMP, probiotics 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.

Profermin Plus®

Fresubin, dietary supplement DIETARY_SUPPLEMENT

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

Fresubin®

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• liver stiffness ≥15 kPa and asymptomatic and/or
• New liver biopsy (\<6months) with at least F3 fibrosis (kleiner) and/or
• Liver biopsy older that 6 months with liver stiffness ≥10 kPa
• Understand and speak Danish written and orally
• Informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Odense University Hospital: lead
• Region of Southern Denmark: collaborator
• Odense Patient Data Explorative Network: collaborator
• University of Southern Denmark: collaborator
• Nordisk Rebalance A/S: collaborator

Study Sites (2)

FLASH - Centre of Liver Research

Odense, Fyn, 5000, Denmark

Location

Odense University Hospital

Odense, 5000, Denmark

Location

MeSH Terms

Conditions

Liver Diseases, Alcoholic; Liver Cirrhosis, Alcoholic; Liver Cirrhosis

Interventions

Probiotics; Fresubin; Dietary Supplements

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Pathologist will perform outcome assessment blinded
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, PhD, Cand.Med.

Model Details: Patients will be randomized 1:1 to receive Profermin Plus® versus a general FSMP, Fresubin®, for 24 weeks.

Study Record Dates

• First Submitted: February 28, 2019
• First Posted: March 5, 2019
• Study Start: March 1, 2019
• Primary Completion: July 15, 2021
• Study Completion (Estimated): February 1, 2031
• Last Updated: November 7, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)