Nonalcoholic steatohepatitis [NASH] Digestive System Nonalcoholic steatohepatitis [NASH]
Conditions
Interventions
The intervention is a low-energy total diet replacement programme with behavioural support (TDR) and has three phases. Phase 1 starts with sole source TDR for up to 12 weeks. Participants will consume
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: BMI >=30 kg/m² and histological evidence of NASH and fibrosis stage 1a to 3
Exclusion criteria
Exclusion criteria: 1. ALT 10x upper limit of normal or above 2. Total bilirubin > 25.5 µmol/l 3. Evidence of other known forms of known chronic liver disease such as alcoholic liver disease, hepatitis B, hepatitis C, primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis, Wilson disease, iron overload, alpha-1-antitrypsin deficiency, drug-induced liver injury, known or suspected hepatocellular carcinoma (HCC) 4. Previous liver transplant or current placement on a liver transplant list 5. High risk of alcohol dependence defined as a score of 8 and above in the alcohol screening tool (AUDIT-C) 6. Consumption of more than 14 units of alcohol over the last week 7. Previous or planned bariatric surgery or ileal resection 8. History of biliary diversion 9. Acute cholecystitis or acute biliary obstruction 10. Contraindication to MRI 11. Currently attending or having attended within 3 months prior to study enrolment a weight management programme including behavioural programmes and weight loss medication 12. Weight loss of 5% or more since biopsy 13. Current insulin use 14. HbA1c > 9% (>75mmol/mol) 15. Diagnosed with type 2 diabetes with substantial changes in medication within the past 3 months 16. If taking GLP-1 agonists or SGLT2 inhibitors, changes in dosage during the past 6 months 17. Taking medication known to have potential activity against NASH (pioglitazone, Vitamin E) 18. Documented arrhythmia, except atrial fibrillation, or prolonged QT syndrome 19. Taking warfarin 20. Chronic renal failure of stage 4 or 5 21. Scheduled for surgery within 6 months 22. People having active treatment for cancer other than skin cancer treated with curative intent by local treatment only or people taking hormonal or other long-term secondary prevention treatment after initial cancer treatment 23. Currently taking part in other clinical trials 24. Pregnant, breastfeeding, or planning to become pregnant during the course of the study 25. Those that the clinician judges not able to meet the demands of either treatment programme or measurement schedule. This may include severe medical problems not listed above or severe psychiatric problems including substance misuse that make following the treatment programme or adhering to the protocol unlikely
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Before baseline 1. Number of potentially eligible participants 2. Proportion of eligible participants enrolled 3. Reasons for non-enrolment At baseline, 4 weeks, 12 weeks, and 24 weeks: 4. Weight 5. Proportion of sessions attended 6. Reasons for non-adherence 7. Proportion of participants attending their follow-ups out of all enrolled 8. Alcohol intake At 4 weeks, 12 weeks, and 24 weeks: 9. Reasons for dropout At 24 weeks: 10. Feedback questionnaire on intervention | — |
Primary
| Measure | Time frame |
|---|---|
| At baseline, 12 weeks, and 24 weeks: 1. Iron-corrected relaxation time (cT1) values by magnetic resonance imaging (MRI) 2. Liver stiffness by transient elastography (added 16/11/2020: and magnetic resonance elastography) 3. Proton density fat fraction (PDFF) 4. Controlled attenuation parameter 5. Glucose regulation biomarker (HbA1c) 6. Total body fat on bioelectrical impedance 7. Visceral fat on MRI 8. Subcutaneous fat on MRI 9. Number and dose of medication 10. Diversity and abundance of the gut microbiome At baseline, 4 weeks, 12 weeks, and 24 weeks: 11. Liver blood biomarkers (ALT, AST, ALP, bilirubin, FIB-4, Apo-F) 12. Renal blood biomarkers (U&E) At 4 weeks, 12 weeks, and 24 weeks: 13. Adverse events | — |
Countries
England, United Kingdom
Outcome results
None listed