MLCT Oil for Fatty Liver - PASS Trial (PASS)

A Randomised Controlled Pilot Study to Test the Role of Medium- and Long-chain Triacylglycerols (MLCT) in Reversing the Phenotype of Non-alcoholic Steatohepatitis (NASH) Patients

The main objective of this randomised pilot study is to explore the relative efficacy of dietary MLCT oil versus LCT oil (corn oil) in augmenting therapy of overweight and obese NAFLD patients with at least a 1-stage reversal between F1 and F4.

Study Overview

• Status: Enrolling by invitation
• Conditions: NAFLD; Non-Alcoholic Fatty Liver Disease; Non-Alcoholic Steatohepatitis
• Intervention / Treatment: Dietary supplement: MLCT Oil; Dietary supplement: LCT Oil (Corn Oil)

Detailed Description

The hypothesis of the study will be that daily intake of MLCT oil is more effective than corn oil in improving either NAFLD or NASH phenotype, with a greater reduction in liver fibrosis stage of participants with NASH.

The single-centre trial is a 2-arm, randomized pilot study with stratification by BMI. Up to 30 participants with biopsy/imaging proven NAFLD / NASH would undergo blinded 1:1 allocation to either control or test group.

All participants would be offered biopsy, whereby a repeat liver biopsy would be undertaken at the end of the study (6 months) to investigate the efficacy of dietary MLCT versus corn oil in augmenting therapy of NASH.

Dietary counselling for the participants will be provided by NUH dietician on 6 weekly basis on how to adhere to the required dietary regimen. For the first 12 weeks, participants are to consume only the 3 provided RTE meals (breakfast, lunch and dinner), with additional fruits or low calories snacks to be advised by dietician. During the second 12-week experimental period, participants will follow strict dietary guideline under the recommendation of the NUH dietician and have oil-containing products [chocolate sauce / oatmeal biscuits] with 30 g of corn or MLCT oil per day.

During the 6 months, study participants would be followed up at 0, 3, 6, 9, 12, 18 and 24 weeks. During each of the follow up visit, the participant would have blood drawn, urine and stool collected as per study schedule.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Between 21 to 65 years old;
• Body mass index (BMI) 23 kg/m2 or higher;
• NAFLD or NASH as determined by liver biopsies within last 2 years with fibrosis stage F1-F4; OR Presence of steatosis and fibrosis via Transient Elastography / MRI
• Participants willing and able to adhere to the prohibitions and restrictions specified in the protocol;
• Participants willing and able to adhere to the dietary prescription as in the study protocol;
• Participants willing and able to provide written informed consent.
• Participants able to read and write English, and own a smartphone with a data plan

Exclusion Criteria:

• Poorly controlled diabetes
• Poorly controlled hypertension
• Estimated glomerular filtration rate of less than 60 ml/min/1.73m2;
• Presence of active alcoholic liver disease, chronic viral hepatitis, drug-induced hepatitis; autoimmune hepatitis, and liver cancer;
• A history of Type 1 diabetes mellitus or previous admission for diabetic ketoacidosis;
• Recurrent urinary tract infection (2 or more over the past one year);
• Having any medical condition that would affect metabolism (i.e. Cushing syndrome, known active hyperthyroidism or hypothyroidism);
• Serious medical disease with likely life expectancy less than 5 years;
• Recently started on selected diabetes / hypertensive medications. Must be on stable doses.
• Ongoing eating disorder or significant weight loss or weight gain as defined by change of 5% or more within 12 weeks before screening visit;
• History of any malignancy within 5 years of screening;
• Women who are pregnant or plan to become pregnant;
• Taking alcohol above the limit recommended (i.e. consumed more than 10 g/day for women or 20 g/day for men);
• Participation in other clinical trial in the 30 days before randomization;
• Participants who cannot be followed up for at least 6 weeks (due to health situation or travel);
• Having allergies / intolerances to the ingredients in the prepared meals or oil-containing products of the study;
• Having chronic gastrointestinal disorders;
• Having taken antibiotics in the last 3 months;
• Participants with arthropathy, CVM, CVA disorder or any systemic disorder which render or when intervention may be dangerous.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; MLCT oil (provided through ready to eat meals and snacks)	Dietary supplement: MLCT Oil; 1st 12 weeks: frozen ready to eat meals prepared with the oil Last 12 weeks: own diet with provided snacks containing the oil
Placebo Comparator: Control; Corn oil (provided through ready to eat meals and snacks)	Dietary supplement: LCT Oil (Corn Oil); 1st 12 weeks: frozen ready to eat meals prepared with the oil Last 12 weeks: own diet with provided snacks containing the oil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver Fibrosis	Change in liver fibrosis through liver biopsy or imaging	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Weight	Change in body weight (kg)	6 months
Body fat composition	Change in body fat composition using MRI body profiler (%)	6 months
Blood pressure	Change in blood pressure using blood pressure monitor (mmHg)	6 months
Body circumferences	Change in waist and hip circumference using measuring tape (cm)	6 months
Blood lipid profile (HDL, LDL, Total cholesterol, Triglycerides)	Change in fasting blood lipid profile (mmol/L)	6 months
Fasting Insulin and Glucose	Change in fasting Insulin and Glucose (mmol/L)	6 months
Haemoglobin A1c	Change in HBA1c (mmol/mol)	6 months
Liver function panel (Albumin, Bilirubin, ALT, AST, ALP, LDH, GGT)	Change in Albumin (g/L), bilirubin (umol/L), ALT, AST, ALP, LDH, GGT (U/L)	6 months
Creatinine	Change in serum and urine creatinine (umol/L)	6 months
Beta-hydroxybutyrate	Change in beta-hydroxybutyrate (mmol/L)	6 months
C-peptide	Change in C-peptide (pmol/L)	6 months
Oral glucose tolerance test	Change in glucose level at 120hr timepoint (mmol/L)	6 months
C-reactive protein (CRP)	Change in CRP (mg/L)	6 months
Inflammatory markers - IL-6, IL-1, TNFalpha	Change in inflammatory markers - IL-6, IL-1, TNFalpha	6 months
Gut microflora composition	Change in gut microbiota using gut metagenomics profiling	6 months

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore
• Collaborators: Wilmar International

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2021
• Primary Completion (Anticipated): March 31, 2022
• Study Completion (Anticipated): March 31, 2023

Study Registration Dates

• First Submitted: September 9, 2021
• First Submitted That Met QC Criteria: January 19, 2022
• First Posted (Actual): February 1, 2022

Study Record Updates

• Last Update Posted (Actual): February 25, 2022
• Last Update Submitted That Met QC Criteria: February 8, 2022
• 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
• Other Study ID Numbers: 2019/00618

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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