Dietary Intervention and Intestinal Microbiota in Non-alcoholic Fatty Liver

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University Hospital, Geneva
Sponsor:
Information provided by (Responsible Party):
Prof. Claude Pichard, University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT01477307
First received: November 15, 2011
Last updated: January 1, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
Obesity
Non-alcoholic Fatty Liver Disease (NAFLD)
Other: Hypocaloric diet
Phase 2

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Effect of Dietary Intervention on Intestinal Microbiota in Patients With Non-alcoholic Fatty Liver Disease

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • abundance of fecal abundance of fecal Bacteroidetes [ Time Frame: thrice, at inclusion, day 21 and day 42 ] [ Designated as safety issue: No ]
    Bacterial cells/g caecal content


Secondary Outcome Measures:
  • liver fat content [ Time Frame: twice, at inclusion and day 21 ] [ Designated as safety issue: No ]
    picsel/uni MRI

  • liver function tests [ Time Frame: four times, at screening, inclusion, day 21 and day 42 ] [ Designated as safety issue: No ]
    mmol/l

  • CRP [ Time Frame: thrice, at screening, inclusion and day 21 ] [ Designated as safety issue: No ]
    mg/l

  • serum cytokines [ Time Frame: twice, at inclusion and day 21 ] [ Designated as safety issue: No ]
    ng/ml

  • serum LPS [ Time Frame: twice, at inclusion and day 21 ] [ Designated as safety issue: No ]
    pg/ml

  • Breath test pullulation [ Time Frame: twice, at inclusion and day 21 ] [ Designated as safety issue: No ]
  • intestinal permeability [ Time Frame: twice, at inclusion and day 21 ] [ Designated as safety issue: No ]
    Polyethylene glycol 3350/Polyethylene glycol 400 ratio

  • body composition [ Time Frame: thrice, at inclusion, day 21 and day 42 ] [ Designated as safety issue: No ]
    body composition in kg and % of body weight

  • liver lipid composition (biopsy) [ Time Frame: once, at screening ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: July 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
hypocaloric diet
The included patients are assigned to a hypocaloric standardized diet for 3 weeks.
Other: Hypocaloric diet
Eurodiet,standardized hypo-caloric diet, during 3 weeks
Other Name: eurodiet 2

  Hide Detailed Description

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

Inability or unwillingness to give consent 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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01477307

Contacts
Contact: Claude Pichard, MD,PhD +41 22 37 29 349 claude.pichard@unige.ch
Contact: Zoltan Patakay, MD +41 79 58 290 Zoltan.Pataky@hcuge.ch

Locations
Switzerland
Geneva University Hospital Recruiting
Geneva, Switzerland, 1211
Contact: Claude Pichard, MD    +41 22 37 29 349    claude.pichard@unige.ch   
Contact: Alain Golay, MD    +41 22 372 97 04    Alain.Golay@hcuge.ch   
Principal Investigator: Claude Pichard, MD         
Sub-Investigator: Antoine Hadengue, MD         
Sub-Investigator: Jacques Schrenzel, MD         
Sub-Investigator: Sylvain Terraz, MD         
Sub-Investigator: Alain Golay, MD         
Sub-Investigator: Laura Rubbia-Brandt, MD         
Sub-Investigator: Vladimir Lazarevic, MD         
Sub-Investigator: Laurence Genton, MD         
Sub-Investigator: Zoltan Patakay, MD         
Sponsors and Collaborators
University Hospital, Geneva
Investigators
Principal Investigator: Claude Pichard, MD Geneva University Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Prof. Claude Pichard, Head, Clinical Nutrition, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT01477307     History of Changes
Other Study ID Numbers: 10-231
Study First Received: November 15, 2011
Last Updated: January 1, 2014
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Geneva:
obesity
non-alcoholic fatty liver disease

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Obesity
Body Weight
Digestive System Diseases
Nutrition Disorders
Overnutrition
Overweight
Signs and Symptoms

ClinicalTrials.gov processed this record on October 23, 2014