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

NCT05506488 | Completed Phase 1 DMC

• 1 other identifier: 2022.0213
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

NASH With Fibrosis; Liver Fibrosis; NAFLD

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is the binary outcome improvement of fibrosis with at least 1-point without worsening of fibrosis and NAFLD score based on histology after 21 weeks (yes/no). Individuals will be labeled as responder or non-responder.

  As assessed on the obtained liver biopsies before and after the treatment

  21 week

Secondary Outcomes (39)

• Mean change in number of senescent cells at baseline and end of treatment

  21 week

• Percent of patients with reversal of NAFLD (Steatosis without ballooning and with or without mild inflammation) and no worsening of fibrosis) from baseline to end of treatment

  21 week

• Global hepatic mRNA expression baseline to end of treatment

  21 week

• Change in NAFLD activity score (NAS)

  21 week

• change in Activity component of steatosis-activity-fibrosis (SAF) score: steatosis -1 point, lobular inflammation -1 point, ballooning -1 point

  21 week

Study Arms (2)

Dasatinib plus Quercetin

ACTIVE COMPARATOR

Day 0: (15 per arm, randomization). week 7: blood, fibroscan, ECG, questionnaires. week 14: blood, fibroscan, ECG, questionnaires. Week 21: blood, fibroscan, ECG, questionnaires, liver biopsy. end of study

Drug: Dasatinib 100 MG + Quercetin (1000 MG)

placebo

PLACEBO COMPARATOR

Day 0: (15 per arm, randomization). week 7: blood, fibroscan, ECG, questionnaires. week 14: blood, fibroscan, ECG, questionnaires. Week 21: blood, fibroscan, ECG, questionnaires, liver biopsy. end of study

Other: Placebo

Interventions

Placebo OTHER

The placebo group will receive intermittent orally administered placebo tablets on three consecutive days for three consecutive weeks followed by a four-week medication free period. This cycle will be repeated three times.

placebo

Dasatinib 100 MG + Quercetin (1000 MG) DRUG

The intervention group will receive intermittent orally administered dasatinib (100 mg/day) plus quercetin (1000 mg/day) on three consecutive days for three consecutive weeks followed by a four-week medication free period. This cycle will be repeated three times.

Dasatinib plus Quercetin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Amsterdam UMC location AMC

Amsterdam, Netherlands

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Liver Cirrhosis

Interventions

Dasatinib; Quercetin

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Flavonols; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Max Nieuwdorp, MD, PhD

  Amsterdam UMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double blind randomized trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Model Details: Double-blind randomized controlled proof-of-principle study

Study Record Dates

• First Submitted: August 15, 2022
• First Posted: August 18, 2022
• Study Start: July 5, 2023
• Primary Completion: February 26, 2026
• Study Completion: February 26, 2026
• Last Updated: April 15, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)