Liver Fibrosis Clinical Trial
— SYN-ALDOfficial title:
Profermin®: Prevention of Progression in Alcoholic Liver Disease by Modulating Dysbiotic Microbiota - a Randomized Controlled Clinical Trial
Verified date | November 2023 |
Source | Odense University Hospital |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 56 |
Est. completion date | February 2031 |
Est. primary completion date | July 15, 2021 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 30 Years to 75 Years |
Eligibility | 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) |
Country | Name | City | State |
---|---|---|---|
Denmark | FLASH - Centre of Liver Research | Odense | Fyn |
Denmark | Odense University Hospital | Odense |
Lead Sponsor | Collaborator |
---|---|
Odense University Hospital | Nordisk Rebalance A/S, Odense Patient Data Explorative Network, Region of Southern Denmark, University of Southern Denmark |
Denmark,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Hepatic a-SMA activity | Reduction in hepatic a-SMA activity | 24 weeks | |
Secondary | Hepatic inflammation | Evaluated by hepatic inflammation markers and metabolites | 24 weeks | |
Secondary | Alfa-smooth muscle actin concentration | Reduction in circulating a-smooth muscle actin concentration | 24 weeks | |
Secondary | Hepatic venous pressure gradient (HVPG) | Reduction in portal pressure measured by the HVPG in unit mmhg | 24 weeks | |
Secondary | Reduction in non-invasive fibrosis markers | Reduction in Ultrasound shear wave elastography (transient and 2-dimensional) (kPa) | 24 weeks | |
Secondary | Reduction in non-invasive fibrosis markers | ProC3 and ProC4 (ng/ml) | 24 weeks | |
Secondary | Reduction in non-invasive fibrosis markers | ELF test | 24 weeks | |
Secondary | Reduction in non-invasive fibrosis markers | Forns index | 24 weeks | |
Secondary | Reduction in non-invasive fibrosis marker | APRI score | 24 weeks | |
Secondary | Reduction in non-invasive fibrosis markers | FIB4 (points) | 24 weeks | |
Secondary | Markers of liver inflammation | Reduction in circulating markers of liver inflammation (cytokeratin-18 degradation products M30 and M65) | 24 weeks | |
Secondary | Improvement of liver histological lesions | 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] |
24 weeks | |
Secondary | Improvement in gut dysbiosis | 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 |
24 weeks | |
Secondary | Liver vein outflow of microbial products | Change in Liver vein outflow of microbial products | 24 weeks | |
Secondary | Lipid profile | Improvement of lipid profile defined as:
Rising HDL, decrease in triglycerids, LDL and total cholesterol |
24 weeks | |
Secondary | Any changes in non-invasive markers of steatosis | Controlled Attenuation Parameter(CAP) and ultrasonographic steatosis assessment (bright liver echo pattern) | 24 weeks | |
Secondary | Individual domains of NAS scoring systemt | 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 (%) | 24 weeks | |
Secondary | Metabolic changes | Water soluble metabolites in circulation will be evaluated with metabolomics | 24 weeks | |
Secondary | Changes in circulating cytokines | Cytokines related to cardiovascular disease and inflammation will be analysed | 24 weeks | |
Secondary | Changes in hepatic macrophage activity | Changes in digital imaging analysis of hepatic CD163 expression in liver biopsies | 24 weeks | |
Secondary | Changes in intestinal fibrosis markers | C4M generated by decomposition of type 4 collagen | 24 weeks | |
Secondary | Changes in intestinal fibrosis markers | CPA9-HNE a fragment degraded from calprotectin | 24 weeks | |
Secondary | Changes bile acids | Changes in bile acids will be measured in both stool and circulation | 24 weeks | |
Secondary | Metabolic changes | Amino acids in circulation will be evaluated with metabolomics | 24 weeks | |
Secondary | Metabolic changes | Lipidomics in circulation will be evaluated with metabolomics | 24 weeks | |
Secondary | Metabolic changes | Lipidomics in liver samples will be evaluated with metabolomics | 24 weeks | |
Secondary | Metabolic changes | Short chain fatty acids in circulation will be evaluated with metabolomics | 24 weeks | |
Secondary | Metabolic changes | Short chain fatty acids in stool samples will be evaluated with metabolomics | 24 weeks |
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