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

Launched by ACADEMISCH MEDISCH CENTRUM - UNIVERSITEIT VAN AMSTERDAM (AMC-UVA) · Aug 16, 2022

Keywords

ClinConnect Summary

This clinical trial is exploring the effects of two medications, dasatinib and quercetin, on liver fibrosis in people with a condition called Non-Alcoholic Fatty Liver Disease (NAFLD) that has caused some scarring in the liver. The study is designed to find out if this combination treatment can help improve liver health in adults who have been diagnosed with NAFLD and have a fibrosis score above a certain level. The trial is currently looking for participants aged 18 and older who meet specific health criteria, such as having stable liver function and agreeing to undergo a follow-up liver biopsy after treatment.

Participants in the trial can expect to take the medications for a set period while being closely monitored by the research team. They will need to attend regular appointments, and their liver health will be evaluated through blood tests and a liver biopsy. This study is important because it could lead to new treatment options for people with liver fibrosis due to NAFLD, a condition that is becoming more common. If you or someone you know is interested in participating, it’s essential to discuss eligibility and any concerns with a healthcare provider.

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Eligibility 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