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Trial record 41 of 54 for:    barley

Profermin®: Prevention of Progression in Alcoholic Liver Disease by Modulating Dysbiotic Microbiota (SYN-ALD)

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ClinicalTrials.gov Identifier: NCT03863730
Recruitment Status : Recruiting
First Posted : March 5, 2019
Last Update Posted : May 20, 2019
Sponsor:
Collaborators:
Region of Southern Denmark
Odense Patient Data Explorative Network
University of Southern Denmark
Nordisk Rebalance A/S
Information provided by (Responsible Party):
Aleksander Krag, Odense University Hospital

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.

Condition or disease Intervention/treatment Phase
Alcoholic Liver Disease Liver Cirrhosis, Alcoholic Probiotics Liver Fibrosis Dietary Supplement: Profermin Plus, FSMP, probiotics Dietary Supplement: Fresubin, dietary supplement Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients will be randomized 1:1 to receive Profermin Plus® versus a general FSMP, Fresubin®, for 24 weeks.
Masking: None (Open Label)
Masking Description: Pathologist will perform outcome assessment blinded
Primary Purpose: Prevention
Official Title: Profermin®: Prevention of Progression in Alcoholic Liver Disease by Modulating Dysbiotic Microbiota - a Randomized Controlled Clinical Trial
Actual Study Start Date : March 1, 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : February 2031

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Diseases

Arm Intervention/treatment
Experimental: 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.
Dietary Supplement: Profermin Plus, FSMP, probiotics
Participants will have to supply their normal intake with Profermin Plus, FSMP, Prbiotics product twice every day for 24 weeks.

Active Comparator: 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.
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.




Primary Outcome Measures :
  1. Hepatic stellate cell activity [ Time Frame: 24 weeks ]
    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.


Secondary Outcome Measures :
  1. Hepatic a-SMA activity [ Time Frame: 24 weeks ]
    Reduction in hepatic a-SMA activity

  2. Hepatic inflammation [ Time Frame: 24 weeks ]
    Evaluated by hepatic inflammation markers and metabolites

  3. Alfa-smooth muscle actin concentration [ Time Frame: 24 weeks ]
    Reduction in circulating a-smooth muscle actin concentration

  4. Hepatic venous pressure gradient (HVPG) [ Time Frame: 24 weeks ]
    Reduction in portal pressure measured by the HVPG in unit mmhg

  5. Reduction in non-invasive fibrosis markers [ Time Frame: 24 weeks ]
    Reduction in Ultrasound shear wave elastography (transient and 2-dimensional) (kPa)

  6. Reduction in non-invasive fibrosis markers [ Time Frame: 24 weeks ]
    ProC3 (ng/ml)

  7. Reduction in non-invasive fibrosis markers [ Time Frame: 24 weeks ]
    ELF test

  8. Reduction in non-invasive fibrosis markers [ Time Frame: 24 weeks ]
    Forns index

  9. Reduction in non-invasive fibrosis marker [ Time Frame: 24 weeks ]
    APRI score

  10. Reduction in non-invasive fibrosis markers [ Time Frame: 24 weeks ]
    FIB4 (points)

  11. Markers of liver inflammation [ Time Frame: 24 weeks ]
    Reduction in circulating markers of liver inflammation (cytokeratin-18 degradation products M30 and M65)

  12. Improvement of liver histological lesions [ Time Frame: 24 weeks ]

    Improvement in semiquantitative liver histological lesions that fulfil at least one of two criteria:

    • At least one stage of liver fibrosis improvement according to the Kleiner fibroses classification (0-4), with no worsening of hepatic inflammatory activity
    • Complete resolution of hepatic inflammatory activity, with no worsening of fibrosis.

    [Worsening defined as an increase of at least one stage of either lobular inflammation or hepatocyte ballooning. Resolution defined as ballooning=0 and lobular inflammation=0-1]


  13. Improvement in gut dysbiosis [ Time Frame: 24 weeks ]

    Defined as:

    • Improved taxonomy, defined as increased relative abundance of species characteristic of healthy individuals and decreased relative abundance of species characteristic of cirrhosis and severe alcoholic liver disease
    • Increase in gut microbial richness

  14. Liver vein outflow of microbial products [ Time Frame: 24 weeks ]
    Change in Liver vein outflow of microbial products

  15. Lipid profile [ Time Frame: 24 weeks ]

    Improvement of lipid profile defined as:

    Rising HDL, decrease in triglycerids, LDL and total cholesterol


  16. Any changes in non-invasive markers of steatosis [ Time Frame: 24 weeks ]
    Controlled Attenuation Parameter(CAP) and ultrasonographic steatosis assessment (bright liver echo pattern)

  17. Individual domains of NAS scoring systemt [ Time Frame: 24 weeks ]
    Any changes in individual domains of the NAS scoring system (fibrosis 0-4, steatosis 0-3, lobular inflammation 0-2, portal inflammation 0-1, ballooning 0-2) or in collagen proportionate area (%)

  18. Metabolic changes [ Time Frame: 24 weeks ]
    Will be evaluated with metabolomics: Water soluble metabolites, Aminoacids, Shortchain fatty acids and Lipidomics.



Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03863730


Contacts
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Contact: Suganya Jacobsen, MD 0045 60148557 suganya.jacobsen@rsyd.dk

Locations
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Denmark
FLASH - Centre of Liver Research Recruiting
Odense, Fyn, Denmark, 5000
Contact: Suganya Jacobsen, MD    004560148557    suganya.jacobsen@rsyd.dk   
Odense University Hospital Recruiting
Odense, Denmark, 5000
Sponsors and Collaborators
Odense University Hospital
Region of Southern Denmark
Odense Patient Data Explorative Network
University of Southern Denmark
Nordisk Rebalance A/S

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Responsible Party: Aleksander Krag, Professor, PhD, Cand.Med., Odense University Hospital
ClinicalTrials.gov Identifier: NCT03863730     History of Changes
Other Study ID Numbers: S-20170163
First Posted: March 5, 2019    Key Record Dates
Last Update Posted: May 20, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Aleksander Krag, Odense University Hospital:
Food for special medical purposes
Gut and liver axis

Additional relevant MeSH terms:
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Liver Diseases
Liver Cirrhosis
Liver Diseases, Alcoholic
Liver Cirrhosis, Alcoholic
Digestive System Diseases
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders