search
Back to results

Investigation of Synbiotic Treatment in NAFLD (INSYTE)

Primary Purpose

Non-Alcoholic Fatty Liver Disease

Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Synbiotic
Maltodextrin
Sponsored by
University Hospital Southampton NHS Foundation Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Alcoholic Fatty Liver Disease focused on measuring non alcoholic fatty liver disease, NAFLD, synbiotic, gut microbiota, intervention, RCT (Randomized Clinical Trial), biomarkers

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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; immunoglobulin A (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).

Sites / Locations

  • Southamption General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Synbiotic

Maltodextrin

Arm Description

Fructo-oligosacharide 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 colony forming unit (CFU)/day (1 capsule a day).

4 grams of maltodextrin daily.

Outcomes

Primary Outcome Measures

Change in Liver Fat
Change in liver fat percent was calculated as the percent liver fat at the end of the study, minus the percent of liver fat prior to the intervention. Change in liver fat percent ranged from -60.6% (good) to + 33.7% (bad).
Change in Enhanced Liver Fibrosis Score (ELF)
Change in Enhanced Liver Fibrosis score (ELF) was calculated as ELF score at the end of the study minus ELF score prior to the intervention (at baseline). A decrease in the ELF score was considered good as it reflected a decrease in liver fibrosis, and an increase in ELF score was considered bad as it reflected an increase in liver fibrosis. Change in ELF scores ranged from -0.56 (good) to + 0.68 (bad).
Change in NAFLD Fibrosis Score
Change in NAFLD Fibrosis Score (NFS) was calculated as the NFS score at the end of the study, minus NFS score prior to the intervention (at baseline). A decrease in the NFS score was considered good because it reflected a decrease in liver fibrosis, and an increase in NFS score was considered bad, as it reflected an increase in liver fibrosis. Change in NFS scores ranged from -2.07 (good) to + 1.75 (bad)
Change in Bifidobacterium Spp.
The change in percent of Bifidobacteria spp was computed as the percent of Bifidobactera spp at the end of the study minus the percent of Bifidobacteria prior to the intervention (at baseline). A positive change in percent (e.g +0.1 to 7.0%) in Bifidobacteria spp. was considered good and a negative change in percent (e.g. -0.1 to -0.5%) in Bifidobacteria spp. considered bad. (Minimum = -0.5% (bad) and Maximum = +7.0% (good)).

Secondary Outcome Measures

Full Information

First Posted
August 24, 2012
Last Updated
January 19, 2021
Sponsor
University Hospital Southampton NHS Foundation Trust
Collaborators
National Institute for Health Research, United Kingdom
search

1. Study Identification

Unique Protocol Identification Number
NCT01680640
Brief Title
Investigation of Synbiotic Treatment in NAFLD
Acronym
INSYTE
Official Title
Investigation of the Effects of a Synbiotic on Liver Fat, Disease Biomarkers and Intestinal Microbiota in Non-alcoholic Fatty Liver Disease
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
December 2013 (undefined)
Primary Completion Date
January 2019 (Actual)
Study Completion Date
January 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Southampton NHS Foundation Trust
Collaborators
National Institute for Health Research, United Kingdom

4. Oversight

Data Monitoring Committee
No

5. Study Description

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 (National Health Service) 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Alcoholic Fatty Liver Disease
Keywords
non alcoholic fatty liver disease, NAFLD, synbiotic, gut microbiota, intervention, RCT (Randomized Clinical Trial), biomarkers

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
104 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Synbiotic
Arm Type
Active Comparator
Arm Description
Fructo-oligosacharide 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 colony forming unit (CFU)/day (1 capsule a day).
Arm Title
Maltodextrin
Arm Type
Placebo Comparator
Arm Description
4 grams of maltodextrin daily.
Intervention Type
Dietary Supplement
Intervention Name(s)
Synbiotic
Intervention Description
The synbiotic to be used is fructo-oligosacharide 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 Type
Dietary Supplement
Intervention Name(s)
Maltodextrin
Primary Outcome Measure Information:
Title
Change in Liver Fat
Description
Change in liver fat percent was calculated as the percent liver fat at the end of the study, minus the percent of liver fat prior to the intervention. Change in liver fat percent ranged from -60.6% (good) to + 33.7% (bad).
Time Frame
baseline and 12 months
Title
Change in Enhanced Liver Fibrosis Score (ELF)
Description
Change in Enhanced Liver Fibrosis score (ELF) was calculated as ELF score at the end of the study minus ELF score prior to the intervention (at baseline). A decrease in the ELF score was considered good as it reflected a decrease in liver fibrosis, and an increase in ELF score was considered bad as it reflected an increase in liver fibrosis. Change in ELF scores ranged from -0.56 (good) to + 0.68 (bad).
Time Frame
baseline and 12 months
Title
Change in NAFLD Fibrosis Score
Description
Change in NAFLD Fibrosis Score (NFS) was calculated as the NFS score at the end of the study, minus NFS score prior to the intervention (at baseline). A decrease in the NFS score was considered good because it reflected a decrease in liver fibrosis, and an increase in NFS score was considered bad, as it reflected an increase in liver fibrosis. Change in NFS scores ranged from -2.07 (good) to + 1.75 (bad)
Time Frame
baseline and 12 months
Title
Change in Bifidobacterium Spp.
Description
The change in percent of Bifidobacteria spp was computed as the percent of Bifidobactera spp at the end of the study minus the percent of Bifidobacteria prior to the intervention (at baseline). A positive change in percent (e.g +0.1 to 7.0%) in Bifidobacteria spp. was considered good and a negative change in percent (e.g. -0.1 to -0.5%) in Bifidobacteria spp. considered bad. (Minimum = -0.5% (bad) and Maximum = +7.0% (good)).
Time Frame
baseline and 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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; immunoglobulin A (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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher D Byrne, MBBCh, PhD
Organizational Affiliation
University of Southampton/University Hospital Southampton NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Southamption General Hospital
City
Southampton
State/Province
Hants
ZIP/Postal Code
SO166YD
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
31987796
Citation
Scorletti E, Afolabi PR, Miles EA, Smith DE, Almehmadi A, Alshathry A, Childs CE, Del Fabbro S, Bilson J, Moyses HE, Clough GF, Sethi JK, Patel J, Wright M, Breen DJ, Peebles C, Darekar A, Aspinall R, Fowell AJ, Dowman JK, Nobili V, Targher G, Delzenne NM, Bindels LB, Calder PC, Byrne CD. Synbiotics Alter Fecal Microbiomes, But Not Liver Fat or Fibrosis, in a Randomized Trial of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2020 May;158(6):1597-1610.e7. doi: 10.1053/j.gastro.2020.01.031. Epub 2020 Jan 25.
Results Reference
derived
PubMed Identifier
29787859
Citation
Scorletti E, Afolabi PR, Miles EA, Smith DE, Almehmadi A, Alshathry A, Moyses HE, Clough GF, Wright M, Patel J, Bindels L, Delzenne NM, Calder PC, Byrne CD. Design and rationale of the INSYTE study: A randomised, placebo controlled study to test the efficacy of a synbiotic on liver fat, disease biomarkers and intestinal microbiota in non-alcoholic fatty liver disease. Contemp Clin Trials. 2018 Aug;71:113-123. doi: 10.1016/j.cct.2018.05.010. Epub 2018 May 19.
Results Reference
derived
PubMed Identifier
26602219
Citation
Byrne CD, Targher G. Time to Replace Assessment of Liver Histology With MR-Based Imaging Tests to Assess Efficacy of Interventions for Nonalcoholic Fatty Liver Disease. Gastroenterology. 2016 Jan;150(1):7-10. doi: 10.1053/j.gastro.2015.11.016. Epub 2015 Nov 18. No abstract available.
Results Reference
derived
PubMed Identifier
24743428
Citation
Byrne CD, Targher G. Ectopic fat, insulin resistance, and nonalcoholic fatty liver disease: implications for cardiovascular disease. Arterioscler Thromb Vasc Biol. 2014 Jun;34(6):1155-61. doi: 10.1161/ATVBAHA.114.303034. Epub 2014 Apr 17.
Results Reference
derived

Learn more about this trial

Investigation of Synbiotic Treatment in NAFLD

We'll reach out to this number within 24 hrs