2024-517593-21-00招募中2 期
Dasatinib and quercetin, a combination of senolytics to treat fibrotic non-alcoholic fatty liver disease; The TRUTH study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
To examine the effect of oral dasatinib plus quercetin on liver fibrosis as assessed by histology in individuals with biopsy-proven NAFLD with fibrosis by performing a double‐blind randomized controlled proof‐of‐principle study. 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).
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Adult individuals, age > 18 ≤70 years
- •NAFLD according to Non-invasive liver tests (FIB-4, APRI)
- •Individuals agree to have a liver biopsy performed after the treatment
- •Compensated liver disease with the following hematologic and biochemical criteria on entry into study: o ALAT <10x ULN o Hemoglobin > 11g/dL for females and 12 g/dL for males o White blood cell (WBC) > 2.5 K/ μL o Neutrophil count > 1.5 K μL o Platelets > 100 K/μL o Total bilirubin <35 μmol/L o Albumin >30 g/L o TP >80% or INR <1.4 o Serum creatinine <1.3 mg/dL (men) or <1.1 mg/dL (women) or estimated glomerular filtration rate (eGFR) > 60mL/min/1.73m
- •Have a stable weight defined by no more than a 5% loss of initial body weight
- •Negative pregnancy test or post-menopausal. Women with childbearing potential (i.e. fertile, following menarche and until becoming postmenopausal unless permanently sterile) must be using a highly effective method of contraception (i.e. combined (estrogen and progestogen containing) hormonal/ progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormonereleasing system, bilateral tubal occlusion, vasectomised partner, sexual abstinence)
- •Subjects should be able to give informed consent
排除标准
- •Evidence of another form of liver disease
- •Contra-indication for liver biopsy
- •History of/or current cardiac dysrhythmias and/or a history of cardiovascular events including myocardial infarction, except patients with only well-controlled hypertension
- •QTc >450 msec on ECG
- •individuals who are lactose hypersensitive or have lactase deficiency
- •Pregnancy/lactation or inability to adhere to adequate contraception in women of child- bearing potentia
- •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
- •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 unstable glycaemic control introduction of an antidiabetic or 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
- •Body mass index (BMI) >45 kg/m2
- •Type 1 diabetes
- •Haemostasis disorders or current treatment with anticoagulants
结局指标
主要结局
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.
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.
次要结局
- Mean change in number of senescent cells at baseline and end of treatment (week 21)
- 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 (week 21).
- Global hepatic mRNA expression baseline to end of treatment (week 21)
- Change from baseline to week 21 in NAFLD activity score (NAS)
- Activity component of steatosis-activity-fibrosis (SAF) score: steatosis -1 point, lobular inflammation -1 point, ballooning -1 point EPOS score a 7 item scoring system (0-6) which represent the seven stages of fibrosis.
- Change from baseline to week 21 in: Fibrosis-4 score (Fib-4 score) and NAFLD Fibrosis Score (NFS) Liver enzymes and synthesis function: ALT, AST and yGT, albumin, INR Liver stiffness and liver steatosis (with controlled attenuation parameter) measurement by Fibroscan
- Change from baseline to 21 weeks in: Glycosylated haemoglobin type A1c (HbA1c), Fasting plasma glucose (FPG), Fasting insulin and glucagon , Homeostatic model assessment of insulin resistance (HOMA-IR) , Glucose day curve (Freestyle libre)
- Change from baseline to 21 weeks in: RAND-36 and EQ-5D-5L: physical and mental component summary scores and scores on the individual sub-domains: Physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health.
- Safety endpoints
- Change from baseline to 21 weeks in: Pulse and ECG , Physical examination ,Haematology (haemoglobin, thrombocytes, erythrocytes, leucocytes, differential count) , Biochemistry (creatinine, creatinine phosphokinase, urea, bilirubin (total), alkaline phosphatase, ferritin, sodium, potassium, calcium. Fecal microbiota composition (morning stool and bile acids)
研究者
Prof. Nieuwdorp
Scientific
Amsterdam UMC Stichting
研究点 (1)
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