E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Accumulation of scar tissue in the liver (fibrosis) may lead to the levelopment of liver cirrhosis. Liver cirrhosis is associated with a variety of complications and decreased survival. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016648 |
E.1.2 | Term | Fibrosis liver |
E.1.2 | System Organ Class | 100000004871 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
We hypothesise that the gut microbiota is a major contributor to progression of fibrosis in alcoholic liver disease and that modulating gut flora by rifaximn halter disease progression. |
|
E.2.2 | Secondary objectives of the trial |
The effects of rifaximin on the gut microbiota, metabolomics and metatranscriptomic |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Liver fibrosis estimated by an Ishak score from 1-4
2. Women of child-bearing potential should use safe anti-conception and provide a negative pregnancy test.
|
|
E.4 | Principal exclusion criteria |
1. Known allergy to rifaximin
2. The investigator judge that the patient would not be compliant with trial medicine
3. Antibiotic treatment the prior 4 weeks
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Rifaximin increases the proportion of patients with an improvement in Ishak score of liver biopsies equal to or more than 1 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Rifaximin reduces the surrogate markers of fibrosis: collagen proportionate area, hydroxylprolin level, TIMP-1, MMP2, key pro-fibrotic cytokines (TGF-β1, PDGF-β-R, CTGF) and key pro-inflammatory cytokines (TNF-α, MCP-1) and CD 163
2. Rifaximin inhibits activation of hepatic stellate cells estimated by a reduction in the area of α-smooth muscle actin positive cells
3. Rifaximin changes the composition of the microbiota estimated by 454 pyrusequencing technology of faecal samples
4. Rifaximin changes gene expression of the microbiota estimated by transscriptomic of faecal samples
5. Rifaximin reduces host pro-inflammatory gene expression in hepatic tissue estimated by transcriptomics and microRNA profiling
6. Rifaximin affects host metabolomics of blood and urine including micro-RNA profile
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 68 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |