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Investigation of Synbiotic Treatment in NAFLD (INSYTE)

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ClinicalTrials.gov Identifier: NCT01680640
Recruitment Status : Recruiting
First Posted : September 7, 2012
Last Update Posted : November 16, 2018
Sponsor:
Collaborator:
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
University Hospital Southampton NHS Foundation Trust

Tracking Information
First Submitted Date  ICMJE August 24, 2012
First Posted Date  ICMJE September 7, 2012
Last Update Posted Date November 16, 2018
Study Start Date  ICMJE December 2013
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 6, 2012)
  • Change in biomarkers for NAFLD and change in liver fat [ Time Frame: 12 months ]
    Primary outcome measures will be: Liver fat determined by magnetic resonance spectroscopy.
  • Change in biomarkers for NAFLD and change in liver fat [ Time Frame: 12 months ]
    Primary outcome measures will be: Serum hyaluronic acid (HA), serum amino-terminal pro-peptide of type III collagen (PIIINP) and tissue inhibitor matrix metalloproteinase 1 (TIMP-1) concentrations; and a composite liver fibrosis score generated from concentrations of these three analytes.
  • Change in biomarkers for NAFLD and change in liver fat [ Time Frame: 12 months ]
    Primary outcome measures will be: Gut microbiota composition determined by 16S rRNA, FISH and qPCR.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01680640 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2012)
  • Change in adipose tissue inflammation, satiety and risk factors for type 2 diabetes. [ Time Frame: 12 months ]
    Secondary outcome measures: Liver fibrosis determined by transient elastography
  • Change in adipose tissue inflammation, satiety and risk factors for type 2 diabetes. [ Time Frame: 12 months ]
    Secondary outcome measures: Insulin and glucose concentrations and hepatic insulin sensitivity
  • Change in adipose tissue inflammation, satiety and risk factors for type 2 diabetes. [ Time Frame: 12 months ]
    Secondary outcome measures: Microvascular function
  • Change in adipose tissue inflammation, satiety and risk factors for type 2 diabetes. [ Time Frame: 12 months ]
    Secondary outcome measures: Plasma cardiovascular risk markers
  • Change in adipose tissue inflammation, satiety and risk factors for type 2 diabetes. [ Time Frame: 12 months ]
    Secondary outcome measures: Adipose tissue and blood markers of metabolism and inflammation
  • Change in adipose tissue inflammation, satiety and risk factors for type 2 diabetes [ Time Frame: 12 months ]
    Secondary outcome measures: De novo lipogenesis
  • Change in adipose tissue inflammation, satiety and risk factors for type 2 diabetes. [ Time Frame: 12 months ]
    Secondary outcome measures: Satiety and satiety factors
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Investigation of Synbiotic Treatment in NAFLD
Official Title  ICMJE Investigation of the Effects of a Synbiotic on Liver Fat, Disease Biomarkers and Intestinal Microbiota in Non-alcoholic Fatty Liver Disease
Brief Summary

Non-alcoholic fatty liver disease (NAFLD) is a liver condition in which fat builds up in the liver not caused by alcohol. The liver is an organ that is not designed to build up fat. NAFLD is common in people who have too much body fat in their abdomen or who have diabetes (high blood sugar), but does not always exist with these conditions. NAFLD can also occur in thin people too. NAFLD can be harmful to the liver and may cause the liver to fail over time. NAFLD may also cause adult (or type 2) diabetes and also heart disease. In people who already have diabetes, NAFLD can cause glucose (sugar) levels to be too high.

Our intestines (guts) contain healthy bacteria and some harmful bacteria (bugs). This balance of healthy and harmful bugs is essential for the normal workings of our intestine to digest food. Providing these bacteria do not leak out into the blood they do not cause harm. If the balance of healthy to harmful bugs is upset, the harmful can cause problems and leak out into the blood. Because the liver is connected to the intestine by blood vessels the harmful bacteria can get to the liver and cause problems. These bacteria can cause the liver and the body to build up too much fat and might cause NAFLD and obesity. In this study, we will test the effects of a supplement (synbiotic) taken during the day, that contains a mixture of 'good' healthy bacteria (probiotic) and a sugar (prebiotic) that is not broken down and absorbed into the blood. We will test whether the synbiotic supplement has beneficial effects on the NAFLD liver condition and on factors linked to too much body fat, diabetes and heart disease.

Detailed Description

We will recruit people with NAFLD who have been diagnosed as part of their NHS care with having this condition. At present there is no treatment for this condition.

Purpose and design:

We are asking the research question: "Does the modulation of gut microflora with a synbiotic improve non-alcoholic fatty liver disease and the related risk factors for heart disease and type 2 diabetes?"

Presently there is no treatment for this liver condition. Research evidence suggests that a synbiotic supplement might be beneficial for this condition.

To address this research question we want to undertake a randomised double blind placebo controlled trial recruiting people who have been diagnosed with NAFLD.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Non-Alcoholic Fatty Liver Disease
Intervention  ICMJE
  • Dietary Supplement: Synbiotic
    The synbiotic to be used is fructo-oligosachharide with a degree of polymerization < 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day).
  • Dietary Supplement: Maltodextrin
Study Arms  ICMJE
  • Active Comparator: Synbiotic
    Fructo-oligosachharide with a degree of polymerization < 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day).
    Intervention: Dietary Supplement: Synbiotic
  • Placebo Comparator: Maltodextrin
    4 grams of maltodextrin daily.
    Intervention: Dietary Supplement: Maltodextrin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 6, 2012)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2019
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Both men and women
  • Age > 18 years
  • Liver fat diagnosed on normal clinical grounds including in most cases liver assessed by Kleiner scoring system to classify severity, with no known aetiological factors for underlying liver disease (e.g. exclusion of hepatitis A, B & C, primary biliary cirrhosis, autoimmune hepatitis, haemochromatosis). Last liver biopsy will be within 3 years of recruitment to the study.
  • Liver fat diagnosed by ultrasound, CT or magnetic resonance imaging (MRI) in patients who also have either diabetes and/or features of the metabolic syndrome, without evidence of known aetiological factors for underlying liver disease (e.g. exclusion of hepatitis A, B & C, primary biliary cirrhosis, autoimmune hepatitis, haemochromatosis).
  • Alcohol consumption ≤ 14 units / week for women ≤ 21 units / week for men.

Exclusion Criteria:

  • Alcohol consumption > 15 units /week for women and > 22 units /week for men.
  • Decompensated acute or chronic liver disease.
  • A history of viral hepatitis, diarrhoea, diverticulosis, irritable bowel syndrome, inflammatory bowel diseases, coeliac disease (seropositivity for anti-endomysial immunoglobulin A antibodies; IgA EMA).
  • Previous bariatric or other abdominal surgery.
  • Continuous use of antibiotics that may change gut microflora, probiotics, or antisecretory drugs capable of causing achlorhydria within the 2 months preceding enrolment, or evidence of immunoglobulin A or immunoglobulin deficiency (both of which produce confounding effects during assessments of intestinal permeability and small intestinal bacterial overgrowth).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Christopher D Byrne, MBBCh, PhD 44 23 8120 5006 C.D.BYRNE@SOUTHAMPTON.AC.UK
Contact: Lucinda C England 44 23 8120 5006 L.C.ENGLAND@SOUTHAMPTON.AC.UK
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01680640
Other Study ID Numbers  ICMJE RHM MED1071
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital Southampton NHS Foundation Trust
Study Sponsor  ICMJE University Hospital Southampton NHS Foundation Trust
Collaborators  ICMJE National Institute for Health Research, United Kingdom
Investigators  ICMJE
Principal Investigator: Christopher D Byrne, MBBCh, PhD University of Southampton/University Hospital Southampton NHS Foundation Trust
PRS Account University Hospital Southampton NHS Foundation Trust
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP