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
|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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|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|
|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|
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.
- 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.
- Hepatic a-SMA activity [ Time Frame: 24 weeks ]Reduction in hepatic a-SMA activity
- Hepatic inflammation [ Time Frame: 24 weeks ]Evaluated by hepatic inflammation markers and metabolites
- Alfa-smooth muscle actin concentration [ Time Frame: 24 weeks ]Reduction in circulating a-smooth muscle actin concentration
- Hepatic venous pressure gradient (HVPG) [ Time Frame: 24 weeks ]Reduction in portal pressure measured by the HVPG in unit mmhg
- Reduction in non-invasive fibrosis markers [ Time Frame: 24 weeks ]Reduction in Ultrasound shear wave elastography (transient and 2-dimensional) (kPa)
- Reduction in non-invasive fibrosis markers [ Time Frame: 24 weeks ]ProC3 (ng/ml)
- Reduction in non-invasive fibrosis markers [ Time Frame: 24 weeks ]ELF test
- Reduction in non-invasive fibrosis markers [ Time Frame: 24 weeks ]Forns index
- Reduction in non-invasive fibrosis marker [ Time Frame: 24 weeks ]APRI score
- Reduction in non-invasive fibrosis markers [ Time Frame: 24 weeks ]FIB4 (points)
- Markers of liver inflammation [ Time Frame: 24 weeks ]Reduction in circulating markers of liver inflammation (cytokeratin-18 degradation products M30 and M65)
- 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]
- Improvement in gut dysbiosis [ Time Frame: 24 weeks ]
- 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
- Liver vein outflow of microbial products [ Time Frame: 24 weeks ]Change in Liver vein outflow of microbial products
- Lipid profile [ Time Frame: 24 weeks ]
Improvement of lipid profile defined as:
Rising HDL, decrease in triglycerids, LDL and total cholesterol
- Any changes in non-invasive markers of steatosis [ Time Frame: 24 weeks ]Controlled Attenuation Parameter(CAP) and ultrasonographic steatosis assessment (bright liver echo pattern)
- 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 (%)
- Metabolic changes [ Time Frame: 24 weeks ]Will be evaluated with metabolomics: Water soluble metabolites, Aminoacids, Shortchain fatty acids and Lipidomics.
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
|Contact: Suganya Jacobsen, MD||0045 firstname.lastname@example.org|
|FLASH - Centre of Liver Research||Recruiting|
|Odense, Fyn, Denmark, 5000|
|Contact: Suganya Jacobsen, MD 004560148557 email@example.com|
|Odense University Hospital||Recruiting|
|Odense, Denmark, 5000|