Nonalcoholic steatohepatitis Digestive System
Conditions
Interventions
Pharmacological intervention (phytosomal curcumin) vs. placebo
Upon acceptance, patients will be randomly (computer-generated sequence) and double-blindly assigned to phytosomial curcumin 1 g twice
Sponsors
Ospedale Humanitas Gradenigo
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial except for protocol described pre-screening activities which require a separate informed consent. 2. Male or female, aged 18-75 years (both inclusive) at the time of signing informed consent. 3. Histologic evidence of NASH based on experienced pathologist evaluation of a liver biopsy obtained up to 4 weeks before screening. 4. A histological NAS = 4 with a score of 1 or more in each sub-component of the score based on pathologist evaluation. 5. NASH fibrosis stage 1, 2, or 3 according to the NASH CRN fibrosis staging system
Exclusion criteria
Exclusion criteria: 1. Refusal or lacks capacity to give informed consent to participate in the trial. 2. Participation in any clinical trial of an investigational therapy or agent within 12 months of randomisation. 3. Patient (or carer) deemed not competent at using the correct site and technique for subcutaneous injection of the trial treatment (containing dummy drug on practice). 4. NAFLD Activity Score (NAS) 2 drug groups) or allegry to curry or curcumin-based nutraceuticals 7. Presence of any acute/chronic infections or illness that at the discretion of the chief investigator might compromise the patient’s health and safety in the trial. 8. Pregnancy or breastfeeding. 9. Women, of childbearing age, who are not willing to practise effective contraception (ie, barrier, oral contraceptives, impenon or past medical history of hysterectomy) for the 48-week duration of the trial and for 1 month after the last administration of the drug. 10. Liver disease of other aetiologies (ie, drug-induced, viral hepatitis, autoimmune hepatitis, PBC, PSC, haemochromatosis, A1AT deficiency, Wilsons disease). 11. Average alcohol consumption >20 g/d(males) and >10 g/d(females) (as assessed by a validated questionnaire(AUDIT-10) within the last 5 years. 12. Medical/surgery history of; gastric bypass surgery, orthotopic liver transplant (OLT) or listed for OLT, hepatocellular, pancreatic, thyroid carcinoma, acute or chronic pancreatitis and total parenteral nutrition within 6 months of randomisation. 13. Diagnosis of malignancy within the last 3 years (with the exception of treated skin malignancies). 14. Hepatocellular carcinoma: dysplastic or intermediate nodules to be excluded. Regenerative and other nodules to be included at the discretion of the chief investigator. 15. Alanine aminotransferase or aspartate aminotransferase >10×upper limit of normal. 16. >5% weight loss since the diagnostic liver biopsy was obtained. 17. Recent (within 3 months of the diagnostic liver biopsy or screening visit) or significant change (as judged by the chief investigator) in dose of the following drugs: inducers of hepatic steatosis (steroids (oral/intravenous), methotrexate, amiodarone), orlistat and/or multivitamins/ vitamin E (containing >200% recommended daily amount; >30 mg/day). 18. Known positivity for antibody to HIV. 19. Currently being treated with renal replacement therapy (ie, haemodialysis or peritoneal dialysis). Specific exclusion criteria for participants with T2D 1. Participants receiving thiazolidinediones (TZDs), dipeptidy peptidase (DPP) IV inhibitors and other GLP-1-based therapies. 3. HbA1c =10%.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Histological NASH resolution measured using the NASH Clinical Research Network criteria) after 72 weeks. Liver biopsies will be read and scored by a single pathologist (RP), who will be blinded to patient clinical characteristics and treatment allocation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 17/06/2022: 1. A =1 stage improvement in NAFLD fibrosis stage and no worsening of NASH (with worsening defined as an increase of =1 point in either the lobular inflammation score or the hepatocyte ballooning score according to the NASH Clinical Research Network criteria) after 72 weeks 2. A =2-point improvement in NAFLD activity score (NAS), with at least 1 point improvement in either ballooning or lobular inflammation score according to the NASH Clinical Research Network criteria) after 72 weeks 3. Individual components of the NAFLD activity score (steatosis, hepatocyte ballooning, lobular inflammation) and the Kleiner fibrosis stage. Fibrosis stages 1a, 1b, and 1c were considered stage 1 for the purposes of analysis according to the NASH Clinical Research Network criteria) after 72 weeks 4. Changes from baseline to 48 weeks in serum liver enzyme concentrations, non-invasive biomarkers /scores of liver disease severity(including, but not limited to, cytokeratin 18 fragments, NAFLD fibrosis score, FIB-4), fasting lipid concentrations, glycaemic control (fasting plasma glucose, HbA1c), whole-body insulin resistance (fasting homoeostasis model of assessment of insulin resistance [HOMA-IR] and adipose tissue insulin resistance [ADIPO-IR]), anthropometric measures (body weight, BMI, waist circumference), physical activity and daily dietary consumption. 5. Safety endpoints included adverse events after the start of treatment, biochemical assessments, and clinical assessments. Selected events (including deaths, cardiovascular events, and acute pancreatitis) were adjudicated by an independent, external event-adjudication committee, whose members were unaware of the treatment assignments. 6. Change in estimated glomerular fuiltration rate (eGFR) at 18 months 7. Change in albuminuria measured using the albumin/creatinine ratio (ACR) at 18 months Previous secondary outcome measures: 1. A =1 stage improvement in NAFLD fibrosis stage an | — |
Countries
Italy
Outcome results
None listed