Using dasatinib and quercetin to treat liver fibrosis in NAFLD patients
Dasatinib and Quercetin, a Combination of Senolytics to Treat Fibrotic Non-alcoholic Fatty Liver Disease - the TRUTH Study
This study is testing whether a combination of dasatinib and quercetin can help adults with Non-Alcoholic Fatty Liver Disease and significant liver fibrosis feel better and improve their liver health.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years to 65 Years |
| Sex | All |
| Sponsor | Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) Academic / other |
| Drugs / interventions | methotrexate, dasatinib |
| Locations | 1 site (Amsterdam) |
| Trial ID | NCT05506488 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the effects of dasatinib combined with quercetin on liver fibrosis in adults diagnosed with Non-Alcoholic Fatty Liver Disease (NAFLD) who have a fibrosis score greater than 2. The study employs a double-blind, randomized controlled design to ensure unbiased results, with participants receiving either the treatment or a placebo. The aim is to assess the efficacy of this combination therapy in reducing liver fibrosis, a significant predictor of mortality in NAFLD patients. Participants will undergo a liver biopsy before and after treatment to evaluate changes in fibrosis levels.
Who should consider this trial
Good fit: Ideal candidates for this study are adults over 18 years old with biopsy-proven NAFLD and a fibrosis score greater than 2, but without cirrhosis.
Not a fit: Patients with cirrhosis or those who do not meet the specified hematologic and biochemical criteria will likely not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from liver fibrosis due to NAFLD, potentially improving their long-term health outcomes.
How similar studies have performed: While there is limited data on the specific combination of dasatinib and quercetin for this indication, the approach of targeting liver fibrosis in NAFLD is an emerging area of interest with potential for success.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Amsterdam
- Amsterdam UMC location AMC — Amsterdam, Netherlands (Recruiting)
Study contacts
- Principal investigator: Max Nieuwdorp, MD, PhD — Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Study coordinator: Max Nieuwdorp, MD, PhD
- Email: m.nieuwdorp@amsterdamumc.nl
- Phone: +3120 - 566 6612
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.