Fatty Liver, Nutritional and Metabolic Disease
Conditions
Brief summary
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).
Detailed description
Following the screening phase and standardisation week, each participant will experience two, 2-week intervention phases, with a 4-week washout period between interventions. Before and after each intervention period they will attend the Imaging Centre (Sir Peter Mansfield Imaging Centre) for MRI scan measurements and then will attend the Biomedical Research Centre for FibroScan, and blood and stool samples collection. During each intervention phase each participant will be required to consume all the food that has been provided, fill in dietary compliance sheets and complete Visual Analogue Scales (VAS) relating to subjective appetite ratings. Design of the dietary interventions Energy expenditure will be estimated for each participant using the individual's basal metabolic rate calculated from Henry-modified Schofield formula and multiplied by an activity factor based on the IPAQ score physical activity levels. A menu, consisting of meals for 3 days personalised for energy requirement, will be devised (these meals are repeated over 2 weeks) by adjusting a template according to their estimated energy requirement in order to minimise weight change during the intervention phase. The diet consists of normal food closely resembling that described by Bawden et al study. A diet template of 2000 kcal/day with energy proportions distributed as 55% from carbohydrates, 15% from protein and 30% from fat are designed and food quantities will be modified to supply the energy requirements for each participant. Three-day cycle menu plans are designed for each diet (LGI/ HGI). Table 1 shows example template menus for both HGI (a) and LGI (b) diets. The GI values of commercial food items are generated from that reported by Henry et al, as well as Nutritics software databases (Nutritics). The dietary GI of the menu is calculated from GI proportional contribution to total carbohydrate using the equation: GI=∑(Cfood/Ctotal) × GIfood; where Cfood is the amount of carbohydrate contained in each digested food (g), Ctotal is the total carbohydrate in the meal and is the reported GI of the food. The GL of the diet is calculated based on the dietary GI and the amount of carbohydrate provided (the same in both diets) using the following equation: GL=(GIfood × Cfood)/100; where GI is the GI of each digested food and food is the amount of carbohydrate in the food. Food composition analysis and evaluation were performed using Nutritics software (Nutritics, Dublin, Ireland, 2018). Participants will be provided with the food at the start of each 2-week diet period and will be clearly instructed on safe food storage and reheating. They will be required to complete dietary compliance sheet on a daily basis. Instructions on dietary compliance will be given at each study period and the dietary compliance records will be reviewed regularly during the intervention to assess their compliance. For the first 1 week prior to the intervention (1-week standardisation), and during the 4-week wash-out period, participants will be asked to avoid eating probiotics, yoghurt and cultured milk drink; if any, to standardise their gut microbiota and avoid any carry-over effects as shown in previous studies.Meal-timing will be standardised among all participants as much as possible during the intervention as well as during the standardisation period.
Interventions
• 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.
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.
Sponsors
University of Nottingham
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Liver Fat Content From Baseline to End of Each 2-Week Dietary Intervention | Baseline and end of each 2-week dietary intervention period | Change in liver fat content (%) from baseline to the end of each 2-week dietary intervention period (LGI diet and HGI diet) in participants with NAFLD. Liver fat content was measured using magnetic resonance spectroscopy. Values represent liver fat content at 2 weeks minus liver fat content at baseline. Lower values indicate lower liver fat content and may reflect improvement in hepatic steatosis. Show more lines |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Gut Microbiome Alpha Diversity After 2 Weeks of LGI and HGI Diets | Baseline and end of each 2-week dietary intervention period | Change in gut microbiome alpha diversity from baseline to the end of each 2-week dietary intervention period (LGI diet and HGI diet), assessed by 16S rRNA gene sequencing in participants with NAFLD. Higher values indicate greater microbial alpha diversity. Values represent the change from baseline to the end of the intervention period. |
| Change in Gut Microbiome Beta Diversity From Baseline to End of Each 2-Week Dietary Intervention | Baseline and end of each 2-week dietary intervention period | Change in gut microbiome beta diversity from baseline to the end of each 2-week dietary intervention period (LGI diet and HGI diet), assessed by 16S rRNA gene sequencing using UniFrac distance. Beta diversity measures differences in microbial community composition between samples. Lower UniFrac distance values indicate greater similarity between microbial communities, whereas higher values indicate greater dissimilarity. UniFrac distance ranges from 0 to 1, where 0 indicates identical communities and 1 indicates completely distinct communities. Values represent the change from baseline to the end of each intervention period. |
| Change in Blood Glucose Level From Baseline to End of 2-Week Dietary Intervention | Baseline and end of each 2-week dietary intervention period | Change in fasting blood glucose concentration from baseline to the end of each 2-week dietary intervention period (LGI diet and HGI diet), measured using a Horiba automated analyser. Values represent blood glucose at 2 weeks minus blood glucose at baseline. Higher values indicate an increase in blood glucose concentration, whereas lower or negative values indicate a decrease in blood glucose concentration. |
| Blood Insulin Change in Fasting Insulin Concentration From Baseline to End of Each 2-Week Dietary Intervention | Baseline and end of each 2-week dietary intervention period | Change in fasting insulin concentration from baseline to the end of each 2-week dietary intervention period (LGI diet and HGI diet). Values represent insulin concentration at 2 weeks minus insulin concentration at baseline. Lower values indicate lower circulating insulin concentrations. |
| Change in Liver Function Biomarkers From Baseline to End of Each 2-Week Dietary Intervention | 2 Baseline and end of each 2-week dietary intervention period Show more lines | Change in liver function biomarkers from baseline to the end of each 2-week dietary intervention period. Values represent the biomarker concentration at 2 weeks minus the concentration at baseline 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) |
| Change in Blood Lipids Concentration From Baseline to End of Each 2-Week Dietary Intervention Show More Lines | Baseline and end of each 2-week dietary intervention period | Change in fasting blood lipids concentration from baseline to the end of each 2-week dietary intervention period. Values represent triglyceride concentration at 2 weeks minus triglyceride concentration at baseline. The blood lipids biomarkers to be assessed are Total Cholesterol, High-density lipoprotein, low-density lipoprotein, Triglycerides. |
| Change in Gut Hormones Concentration From Baseline to End of Each 2-Week Dietary Intervention | Baseline and end of each 2-week dietary intervention period | Change in gut hormones concentration from baseline to the end of each 2-week dietary intervention period. Values represent GLP-1 concentration at 2 weeks minus GLP-1 concentration at baseline.using radioimmunoassay (RIA) or Sandwich ELISA methods. The blood gut hormones to be assessed were Leptin, Ghrelin,, GLP-1 (Glucagon-like peptide 1). |
| Change in Plasma Short-Chain Fatty Acid Concentrations From Baseline to End of Each 2-Week Dietary Intervention | Baseline and end of each 2-week dietary intervention period | Change in plasma short-chain fatty acid (SCFA) concentrations from baseline to the end of each 2-week dietary intervention period (LGI diet and HGI diet) in participants with NAFLD. Plasma SCFAs (including acetic acid, butyric acid, and valeric acid) were measured in fasting blood samples. Values represent the concentration at the end of the intervention period minus the concentration at baseline. Higher values indicate higher circulating SCFA concentrations. |
| Change in Body Weight From Baseline to End of Each 2-Week Dietary Intervention | Baseline and end of each 2-week dietary intervention period | Change in body weight from baseline to the end of each 2-week dietary intervention period (LGI diet and HGI diet) in participants with NAFLD. Body weight was measured in kilograms using calibrated scales. Values represent body weight at the end of the intervention period minus body weight at baseline. Negative values indicate weight loss, whereas positive values indicate weight gain. |
| Change in Composite Appetite Sensations (CAS) Score From Baseline to End of Each 2-Week Dietary Intervention | Baseline and end of each 2-week dietary intervention period | Composite Appetite Sensations (CAS) score was derived from Visual Analogue Scale (VAS) assessments of appetite. Participants rated hunger, satisfaction, fullness, desire to eat, and prospective food consumption on 10-cm (0-100 mm) visual analogue scales. The CAS score was calculated as: 2 3 \[Hunger + (100 - Satisfaction) + (100 - Fullness) + Desire to Eat + Prospective Food Consumption\] / 5 4 5 CAS scores range from 0 to 100 mm, with higher scores indicating greater overall appetite and lower scores indicating lower appetite. Values represent the change from baseline to the end of each 2-week dietary intervention period. |
Countries
United Kingdom
Contacts
PRINCIPAL_INVESTIGATORGuru Aithal, PhD
University of Nottingham
Participant flow
Pre-assignment details
Twelve eligible participants with NAFLD were randomized to one of two crossover diet sequences: LGI diet followed by HGI diet or HGI diet followed by LGI diet.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 50.8 years STANDARD_DEVIATION 8 |
| Pre-Intervention BMI (LGI vs HGI Groups) | 33.8 Kg/m^2 STANDARD_DEVIATION 6.2 |
| Pre-Intervention Body weight (LGI vs HGI Groups) | 93.9 Kg STANDARD_DEVIATION 17.6 |
| Race and Ethnicity Not Collected | 0 Participants |
| Region of Enrollment United Kingdom | 12 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 0 / 7 | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 |
Outcome results
None listed