Low GI Diet Effects on Non-Alcoholic Fatty Liver Disease (LGI-NAFLD)

Effects of an Iso-energetic Low Glycemic Index (GI) Diet on Liver Fat Accumulation and Gut Microbiota Composition in Patients With Non- Alcoholic Fatty Liver Disease (NAFLD)

A 2 x 2 cross-over dietary intervention trial designed to investigate the effects of low glycemic index (LGI) versus high glycemic index (HGI) diet on hepatic fat accumulation and gut microbiota composition in participants with NAFLD.

Participants will be allocated randomly to a 2-week either high GI (HGI) or low GI (LGI) diet followed by a 4-week wash-out period and then the LGI or HGI diet, opposite to the first 2-weeks (N= 16).

Study Overview

• Status: Recruiting
• Conditions: Fatty Liver; Nutritional and Metabolic Disease
• Intervention / Treatment: Other: low glycemic index diet; Other: High glycemic index diet

• Study Type: Interventional
• Enrollment (Anticipated): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
      • Recruiting
      • NIHR Nottingham Clinical Research Facility Nottingham Digestive Diseases Centre
      • Contact: Amina Al-Awadi; Phone Number: +44 (0)115 823 1073; Email: Amina.Alawadi@nuh.nhs.uk
      • Principal Investigator: Guruprasad Aithal, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • Adult males and females aged from 18 to 65 years (balanced number).

  • Detected NAFLD by CAP-FibroScan™ >288dB/m or by MRI-PDFF) > 5% fat of liver weight.
  • Body mass index ≥ 25 kg/m2
  • Have current moderate to high GI diet intake of ≥ 60 (Assessed from a completed 7-day food diary).
  • Abdominal obesity (Waist circumference > 102 cm for males and > 88 cm for females)
  • Able to give informed consent.
  • Able to undergo MRI/S and CAP-FibroScan™.

Exclusion Criteria:

• • Current smokers and excessive alcohol drinkers (> 14 units/week).

  • Perimenopausal (irregular periods) women.
  • Participants with other liver abnormalities.
  • Participants with history of gastrointestinal surgeries, depression, eating disorders or difficulties.
  • Participants using pharmacologic agents for obesity or NAFLD.
  • Participants with type 1 diabetes.
  • Participants with type 2 diabetes on second line medications (eg GLP-1 analogues, sulfonylureas).
  • Participation in any other trial in the last 3 months.
  • Participants on any special diets (e.g. vegetarians).
  • Intolerance to foods included in the diet plan.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LGI Diet; low glycemic index diet	Other: low glycemic index diet; • Three-day cycle menu of LGI diet will be designed and supplied to each participant in an amount designed to meet their estimated energy requirements. The percentage energy from protein, fat and carbohydrate will be the same in the two diets. Each diet period of the trial will last for two weeks.; Other Names: LGI
Other: HGI Diet; High glycemic index diet	Other: High glycemic index diet; Three-day cycle menu of HGI diet will be designed and supplied to each participant in an amount designed to meet their estimated energy requirements. The percentage energy from protein, fat and carbohydrate will be the same in the two diets. Each diet period of the trial will last for two weeks.; Other Names: HGI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
liver fat content	To assess the difference in liver fat content between LGI and HGI diet groups in participants with NAFLD using MRI/S	At baseline
liver fat content	To assess the difference in liver fat content between LGI and HGI diet groups in participants with NAFLD using MRI/S	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbial composition	To assess the difference in gut microbiota composition between LGI and HGI diet groups in participants with NAFLD using 16S sequencing of rRNA	At baseline
Gut microbial composition	To assess the difference in gut microbiota composition between LGI and HGI diet groups in participants with NAFLD using 16S sequencing of rRNA	2 weeks
Blood glucose level	To assess the differences in blood glucose levels between LGI and HGI diet groups in participants with NAFLD using Horiba automated analyser. .	At baseline
Blood glucose level	To assess the differences in blood glucose levels between LGI and HGI diet groups in participants with NAFLD using Horiba automated analyser.	2 weeks
Blood insulin levels	To assess the differences in blood insulin levels between LGI and HGI diet groups in participants with NAFLD using radioimmunoassay methods .	At baseline
Blood insulin levels	To assess the differences in blood insulin levels between LGI and HGI diet groups in participants with NAFLD using radioimmunoassay methods .	2 weeks
blood liver function tests	To assess the differences in liver function biomarkers between LGI and HGI diet groups in participants with NAFLD using Horiba automated analyser. The blood liver function tests (LFTs) to be assessed are GGT(Gamma-Glutamyl Transferase), ALP(Alkaline Phosphatase), AST(Aspartate Amino Transferase), and ALT(Alanine Amino Transferase)	At baseline
blood liver function test	To assess the differences in liver function biomarkers between LGI and HGI diet groups in participants with NAFLD using Horiba automated analyser. The blood liver function tests (LFTs) to be assessed are GGT(Gamma-Glutamyl Transferase), ALP(Alkaline Phosphatase), AST(Aspartate Amino Transferase), and ALT(Alanine Amino Transferase)	2 weeks
blood lipids levels	To assess the differences in blood lipids levels between LGI and HGI diet groups in participants with NAFLD using Horiba automated analyser. The blood lipids biomarkers to be assessed are Total Cholesterol, Free Fatty Acids, High-density lipoprotein, low-density lipoprotein, Triglycerides.	At baseline
blood lipids levels	To assess the differences in blood lipids levels between LGI and HGI diet groups in participants with NAFLD using Horiba automated analyser. The blood lipids biomarkers to be assessed are Total Cholesterol, Free Fatty Acids, High-density lipoprotein, low-density lipoprotein, Triglycerides.	2 weeks
blood gut hormones levels	To assess the differences in blood gut hormones levels between LGI and HGI diet groups in participants with NAFLD using radioimmunoassay (RIA) or Sandwich ELISA methods. The blood gut hormones to be assessed are Glucagon, Leptin, Ghrelin, PYY (Peptide YY), GLP-1 (Glucagon-like peptide 1).	At baseline
blood gut hormones levels	To assess the differences in blood gut hormones levels between LGI and HGI diet groups in participants with NAFLD using radioimmunoassay (RIA) or Sandwich ELISA methods. The blood gut hormones to be assessed are Glucagon, Leptin, Ghrelin, PYY (Peptide YY), GLP-1 (Glucagon-like peptide 1).	2 weeks
Plasma Short Chain Fatty Acids (SCFAs)	To investigate the differences in plasma SCFAs between LGI and HGI diet groups in participants with NAFLD.	At baseline
Plasma Short Chain Fatty Acids (SCFAs)	To investigate the differences in plasma SCFAs between LGI and HGI diet groups in participants with NAFLD.	2 weeks
Anthropometric measurements	Weight in kg, Height in meters will be combined to report BMI kg/m^2 or each study arm	At baseline
Anthropometric measurements	Weight in kg, Height in meters will be combined to report BMI kg/m^2 or each study arm	2 weeks
Body composition Fat Mass	Bio-electrical Impedance analysis (BIA) will be used to assess the body composition of fat mass %.	At baseline
Body composition Fat Mass	Bio-electrical Impedance analysis (BIA) will be used to assess the body composition of fat mass %.	2 weeks
Body composition Muscle Mass	Bio-electrical Impedance analysis (BIA) will be used to assess the body composition of muscle mass %.	At baseline
Body composition Muscle Mass	Bio-electrical Impedance analysis (BIA) will be used to assess the body composition of muscle mass %.	2 weeks
Body composition Water Content	Bio-electrical Impedance analysis (BIA) will be used to assess the body composition of water content %.	At baseline
Body composition Water Content	Bio-electrical Impedance analysis (BIA) will be used to assess the body composition of water content %.	2 weeks
Visual analogue scales (VAS)	Visual analogue scales (VAS) in 0 to 10 cm scale will be used to assess the participant's subjective appetite (hunger and fullness) during the each study arm.	through study completion, an average of two weeks

Collaborators and Investigators

• Sponsor: University of Nottingham

Publications and helpful links

General Publications

• Al-Awadi A, Grove J, Taylor M, Valdes A, Vijay A, Bawden S, Gowland P, Aithal G. Effects of an isoenergetic low Glycaemic Index (GI) diet on liver fat accumulation and gut microbiota composition in patients with non-alcoholic fatty liver disease (NAFLD): a study protocol of an efficacy mechanism evaluation. BMJ Open. 2021 Oct 7;11(10):e045802. doi: 10.1136/bmjopen-2020-045802.

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2020
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: April 20, 2020
• First Submitted That Met QC Criteria: May 29, 2020
• First Posted (Actual): June 4, 2020

Study Record Updates

• Last Update Posted (Actual): September 29, 2021
• Last Update Submitted That Met QC Criteria: September 28, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Metabolic Diseases
• Other Study ID Numbers: 19042; 262245 (Other Identifier: IRAS); 19/EM/0291 (Other Identifier: REC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Within a five-year timeframe, the final anonymized trial data will be uploaded to the https://rdmc.nottingham.ac.uk public repository after consistency and quality have been verified by the project team and publication of the results. Data from this trial are intended to be presented at local and international conferences including those attended by clinicians and dietitians and will also be used as part of a Philosophy Doctorate thesis. Publications will be in peer reviewed journals. No participant will be identified in any of these publications.
• IPD Sharing Time Frame: within five years time-frame
• IPD Sharing Access Criteria: Public repository. presented at local and international conferences. part of a Philosophy Doctorate thesis
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No