Dietary Intervention and Intestinal Microbiota in Non-alcoholic Fatty Liver
Condition: Obesity; Non-alcoholic Fatty Liver Disease (NAFLD)
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Observational

Summary: 
      In patients with NAFLD/NASH, changes in liver lipid composition and function tests following
      a short dietary intervention are associated with changes in gut microbiota
    

Detailed description: 
      Study Hypothesis: In patients with NAFLD/NASH, changes in liver lipid composition and
      function tests following a short dietary intervention are associated with changes in gut
      microbiota

      Study period:

        -  Study duration for the participant: 7-10 weeks (1-4 weeks screening period, 3 weeks of
           intervention + 3 weeks of follow-up)

        -  Expected study completion date: 30.04.2012 Study type: Single arm before-after study

      Number of patients:

      20 subjects with obesity and NAFLD / NASH

      Main criteria for inclusion:

        -  Obesity defined as BMI>30

        -  Abnormal liver function tests defined as ALT > 1.5 times the upper limit of normal

        -  NAFLD present at liver biopsy

        -  Age > 18 years, < 60 years

      Main exclusion criteria:

        -  Inability or unwillingness to give consent

        -  Parenteral nutrition or other ongoing dietary intervention

        -  Bulimia

        -  Other known cause of chronic liver disease, including hepatitis B or C, iron overload,

        -  Use of substances known to alter intestinal permeability, including alcohol and NSAIDs

      Intervention:

      The phase 2 Eurodiet® program will be used as standardized hypo-caloric diet during a 3-weeks
      intervention period. The products are commercially available and prescribed to reach 1000
      kcal/day. These products will be offered free of charge.

      Primary Objective:

      To assess the impact of dietary intervention on the relative abundance of fecal Bacteroidetes
      (expressed as the bacteroidetes to firmicutes ratio) in patients with obesity, abnormal liver
      function tests and NAFLD

      Secondary Objectives:

        1. To compare fecal microbiota from patients with NAFLD or NASH at baseline

        2. To assess fecal microbiota changes in patients with NAFLD or NASH after dietary
           intervention

        3. To measure liver fat content at baseline and after dietary intervention

        4. To assess changes in liver function tests and ultrasensitive CRP, cytokines and serum
           LPS in relation to changes in microbiota and liver lipid composition

        5. To measure orocecal transit time, an index of intestinal pullulation, at baseline and
           after dietary intervention in patients with NAFLD or NASH

        6. To measure intestinal permeability at baseline and after dietary intervention in
           patients with NAFLD or NASH

        7. To assess body composition changes in relation to changes in microbiota and liver lipid
           composition

      Statistical methods:

      Baseline and end-of-treatment changes for both bacterial genders and subspecies will be
      compared using paired-sample Wilcoxon signed-rank test. ANOVA and paired t-test for
      comparison of other changes within groups. Pearson or Spearman tests will be used to assess
      correlations between changes in microbiota and changes in liver fat content, liver function
      tests, CRP, cytokines and intestinal pullulation and permeability.

      Sample size:

      20 patients with NAFLD/NASH will be studied before and after dietary intervention.

      Assessment of end-points:

      Fecal microbiota will be analysed with 454-Flex metagenomics Ultrasensitive CRP and serum LPS
      changes as compared with baseline Serum cytokines as measured with ELISA Liver fat content
      and composition will be measured using MR spectroscopy Small intestinal overgrowth and
      intestinal permeability will be assessed using standard 13C breath tests and
      polyethyleneglycol absorption test Body mass composition changes will be assessed using
      bioelectrical impedance analysis

      Safety :

      All adverse events will be recorded throughout the study, in compliance with GCP ICH E6 and
      national regulations.
    

Intervention name(s): Hypocaloric diet
Intervention type(s): Other
Intervention description(s): Eurodiet,standardized hypo-caloric diet, during 3 weeks
Other intervention name(s): eurodiet 2
Observational model: Other
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Obesity defined as BMI>30 Abnormal liver function tests defined as ALT > 1.5 times the
        upper limit of normal NAFLD present at liver biopsy Age > 18 years, < 60 years
      
Keywords: obesity; non-alcoholic fatty liver disease