Dasatinib and Quercetin to Treat Fibrotic Non-alcoholic Fatty Liver Disease

• Status: Not yet recruiting
• Trial end date: 2025-10-01
• Target enrollment: 0
• Participant gender: All

Summary

To examine the effect of dasatinib plus quercetin on liver fibrosis in individuals with biopsy proven NAFLD with fibrosis by performing a double-blind randomized controlled proof-of-principle study

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Treatments: Dasatinib; Quercetin

Criteria

Inclusion Criteria:

Adult individuals, age > 18 years

• NAFLD with fibrosis score >2 according to the Steatosis Activity and Fibrosis score, but no cirrhosis histological diagnosis according to the SAF fibrosis score on a liver biopsy performed < 6 months before screening in the study and confirmed by central reading during the screening period.

• Individuals agrees to have a liver biopsy performed after the treatment

• Compensated liver disease with the following hematologic and biochemical criteria on entry into protocol:

• ALAT <10x ULN

• Hemoglobin > 11g/dL for females and 12 g/dL for males

• White blood cell (WBC) > 2.5 K/ μL

• Neutrophil count > 1.5 K μL

• Platelets > 100 K/μL

• Total bilirubin <35 μmol/L

• Albumin >30 g/L

• TP >80% or INR <1.4

• Serum creatinine <1.3 mg/dL (men) or <1.1 mg/dL (women) or estimated glomerular filtration rate (eGFR) > 60mL/min/1.73m2

• Have a stable weight since the liver biopsy was performed defined by no more than a 5% loss of initial body weight

• Subjects should be able to give informed consent

Exclusion Criteria:

• Evidence of another form of liver disease

• History of sustained excess alcohol ingestion: daily consumption >30g/day (3 drinks per day) for males and >20 g/day (2 drinks per day) for females

• Unstable metabolic condition: weight change > 5 kg in the last three months, diabetes with poor glycaemic control (HbA1c > 8.5%), introduction of an antidiabetic or of an anti-obesity drug/malabsorptive or restrictive bariatric (weight loss) surgery in the past 6 months prior to screening

• Bariatric surgery

• ingestion of drugs known to produce hepatic steatosis including corticosteroids, high-dose oestrogens, methotrexate, tetracycline or amiodarone in the previous 6 months

• Significant systemic or major illnesses other than liver disease, including congestive heart failure (class C and D of the AHA), unstable coronary artery disease, cerebrovascular disease, pulmonary disease, renal failure, organ transplantation, serious psychiatric disease, active malignancy, compromised immunity

• Pregnancy/lactation or inability to adhere to adequate contraception in woman of childbearing potential

• Body mass index (BMI) >45 kg/m2

• Type 1 diabetes

• Haemostasis disorders or current treatment with anticoagulants

• Contra-indication to liver biopsy

• History of/or current cardiac dysrhythmias and/or a history of cardiovascular disease event, including myocardial infarction, except patients with only well controlled hypertension

• QTc >450 msec on ECG

• Use of prescribed drugs dependent on CYP3A4 with narrow therapeutic window and strong inducers or inhibitors of CYP3A4

• Use of H2-antagonists and/or Proton Pump Inhibitors