Clinical trial NCT05217745: MLCT Oil for Fatty Liver - PASS Trial
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Non-Alcoholic Fatty Liver Disease
Non-Alcoholic Steatohepatitis
NAFLD
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
Collaborators: name: Wilmar International
First posted: 2022-02-01
Enrollment: 30
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Liver Fibrosis
timeFrame: 6 months
Secondary outcomes:
measure: Body Weight
timeFrame: 6 months
measure: Body fat composition
timeFrame: 6 months
measure: Blood pressure
timeFrame: 6 months
measure: Body circumferences
timeFrame: 6 months
measure: Blood lipid profile (HDL, LDL, Total cholesterol, Triglycerides)
timeFrame: 6 months
measure: Fasting Insulin and Glucose
timeFrame: 6 months
measure: Haemoglobin A1c
timeFrame: 6 months
measure: Liver function panel (Albumin, Bilirubin, ALT, AST, ALP, LDH, GGT)
timeFrame: 6 months
measure: Creatinine
timeFrame: 6 months
measure: Beta-hydroxybutyrate
timeFrame: 6 months
measure: C-peptide
timeFrame: 6 months
measure: Oral glucose tolerance test
timeFrame: 6 months
measure: C-reactive protein (CRP)
timeFrame: 6 months
measure: Inflammatory markers - IL-6, IL-1, TNFalpha
timeFrame: 6 months
measure: Gut microflora composition
timeFrame: 6 months
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: National University Hospital, Singapore
name: Dan Yock Young
role: PRINCIPAL_INVESTIGATOR
References: