Investigation of Synbiotic Treatment in NAFLD

NCT01680640 | Completed Results

• 1 other identifier: RHM MED1071
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Alcoholic Fatty Liver Disease

Keywords

non alcoholic fatty liver disease; NAFLD; synbiotic; gut microbiota; intervention; RCT (Randomized Clinical Trial); biomarkers

Outcome Measures

Primary Outcomes (4)

• 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).

  baseline and 12 months

• 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).

  baseline and 12 months

• 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)

  baseline and 12 months

• 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)).

  baseline and 12 months

Study Arms (2)

Synbiotic

ACTIVE COMPARATOR

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).

Dietary Supplement: Synbiotic

Maltodextrin

PLACEBO COMPARATOR

4 grams of maltodextrin daily.

Dietary Supplement: Maltodextrin

Interventions

Synbiotic DIETARY_SUPPLEMENT

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).

Synbiotic

Maltodextrin DIETARY_SUPPLEMENT

Maltodextrin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Both men and women
• Age \> 18 years
• Alcohol consumption ≤ 14 units / week for women ≤ 21 units / week for men.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University Hospital Southampton NHS Foundation Trust: lead
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (1)

Southamption General Hospital

Southampton, Hants, SO166YD, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 31987796 DERIVED

• 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.

  PMID: 29787859 DERIVED

• 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.

  PMID: 26602219 DERIVED

• 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.

  PMID: 24743428 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Synbiotics; maltodextrin

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Prebiotics; Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Probiotics; Food and Beverages

Limitations and Caveats

We choose one strain of bacteria in the synbiotic. The study was designed as a phase-2 clinical trial using magnetic resonance spectroscopy (MRS) and not liver biopsy. We deliberately did not include a lifestyle intervention as we wanted to test the effect of the synbiotic alone.

Results Point of Contact

• Title: Christopher D Byrne
• Organization: University of Southampton

cdtb@soton.ac.uk

44 (0)23 8120 8818

Study Officials

• Christopher D Byrne, MBBCh, PhD

  University of Southampton/University Hospital Southampton NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2012
• First Posted: September 7, 2012
• Study Start: December 1, 2013
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: February 5, 2021
• Results First Posted: February 5, 2021

Record last verified: 2020-10

Locations

GB (1)