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Investigation of Synbiotic Treatment in NAFLD (INSYTE)

This study is not yet open for participant recruitment.
Verified October 2012 by University Hospital Southampton NHS Foundation Trust.
Sponsor:
Collaborator:
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
University Hospital Southampton NHS Foundation Trust.
ClinicalTrials.gov Identifier:
NCT01680640
First received: August 24, 2012
Last updated: October 1, 2012
Last verified: October 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Non-Alcoholic Fatty Liver Disease
 Dietary Supplement: Synbiotic
Dietary Supplement: Maltodextrin
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Investigation of the Effects of a Synbiotic on Liver Fat, Disease Biomarkers and Intestinal Microbiota in Non-alcoholic Fatty Liver Disease

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University Hospital Southampton NHS Foundation Trust.:

Primary Outcome Measures:
  • Change in biomarkers for NAFLD and change in liver fat [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    Primary outcome measures will be:

    Gut microbiota composition determined by 16S rRNA, FISH and qPCR.



Secondary Outcome Measures:
  • Change in adipose tissue inflammation, satiety and risk factors for type 2 diabetes. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    Secondary outcome measures:

    Microvascular function


  • Change in adipose tissue inflammation, satiety and risk factors for type 2 diabetes. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    Secondary outcome measures:

    Plasma cardiovascular risk markers


  • Change in adipose tissue inflammation, satiety and risk factors for type 2 diabetes. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    Secondary outcome measures:

    De novo lipogenesis


  • Change in adipose tissue inflammation, satiety and risk factors for type 2 diabetes. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    Secondary outcome measures:

    Satiety and satiety factors



Estimated Enrollment: 100
Arms Assigned Interventions
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).
 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).
Placebo Comparator: Maltodextrin
4 grams of maltodextrin daily.
 Dietary Supplement: Maltodextrin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01680640

Contacts
Contact: Christopher D Byrne, MBBCh, PhD 44 2380 795006 C.D.BYRNE@SOUTHAMPTON.AC.UK
Contact: Lucinda C England 44 2380 795006 L.C.ENGLAND@SOUTHAMPTON.AC.UK

Locations
United Kingdom
Southamption General Hospital Not yet recruiting
Southampton, Hants, United Kingdom, SO166YD
Contact: Christopher D Byrne, MBBCH PHD     44 2380 795006     C.D.BYRNE@SOUTHAMPTON.AC.UK    
Contact: Lucinda C England     44 2380 795006     L.C.ENGLAND@SOUTHAMPTON.AC.UK    
Sponsors and Collaborators
University Hospital Southampton NHS Foundation Trust.
National Institute for Health Research, United Kingdom
Investigators
Principal Investigator: Christopher D Byrne, MBBCh, PhD University of Southampton/University Hospital Southampton NHS Foundation Trust
  More Information

No publications provided

Responsible Party: University Hospital Southampton NHS Foundation Trust.
ClinicalTrials.gov Identifier: NCT01680640     History of Changes
Other Study ID Numbers: RHM MED1071
Study First Received: August 24, 2012
Last Updated: October 1, 2012
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: National Health Service

Keywords provided by University Hospital Southampton NHS Foundation Trust.:
non alcoholic fatty liver disease
NAFLD
synbiotic
gut microbiota
 intervention
RCT
biomarkers

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on May 23, 2013