2024-519968-41-00招募中3 期
Efficacy of simvastatin reducing liver fibrosis in patients with advanced fibrosis due to alcohol: a randomized, double-blind, placebo-controlled clinical trial.
Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer1 个研究点 分布在 1 个国家目标入组 90 人开始时间: 2024年12月11日最近更新:
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Change from baseline biopsy in the histological fibrosis score measured using the Ishak scale at 24 months.
研究概览
简要总结
Proportion of patients with a significant reduction in the degree of liver fibrosis after treatment with simvastatin compared to placebo, analyzed through the histological evaluation of fibrosis using the Ishak scale, defined as a reduction in the fibrosis value of at least one point on the scale.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Age ≥ 18 years
- •Chronic alcohol-related liver disease according to international guidelines (EASL, European Association for the Study of the Liver) and with data of significant liver fibrosis obtained in the diagnostic biopsy at the beginning of the study or in the last biopsy of the patient within 6 months prior to randomization. Significant liver fibrosis is defined by a score on the Ishak fibrosis scale of between 3 and
- •Patients in the compensated chronic liver disease phase defined by the absence of clinical decompensations at the time of entering the study, with or without data of portal hypertension.
- •Women of childbearing potential must have a negative urine pregnancy test prior to study enrollment and agree to use highly effective contraceptive methods (combined oral pill, injectable or implanted contraceptive, intrauterine device / hormone delivery system intrauterine) during the study.
排除标准
- •Patients receiving statins or fibrates.
- •Hepatocellular carcinoma of any stage.
- •Patients with known muscle disease.
- •Patients with previous rhabdomyolysis.
- •Patients being treated with strong CYP3A4 enzyme inhibitors (see section 5.2: Concomitant drugs, not allowed and allowed).
- •Patients being treated with drugs with possible interactions with simvastatin (see section 5.2: Concomitant drugs, not allowed and allowed).
- •Patients with a history of significant extrahepatic disease with poor short-term prognosis, including New York Heart Association Grade III / V congestive heart failure, GOLD COPD> 2, chronic kidney disease with serum creatinine> 2mg / dL or under therapy of kidney replacement.
- •Patients with extrahepatic malignancies, including solid tumors and hematologic malignancies.
- •Patients with a history or an increased risk of intestinal obstruction.
- •Pregnancy or breastfeeding.
- •Patients included in other clinical trials during the previous month.
- •Patients with other etiologies of liver disease in addition to alcohol: hepatitis C, hepatitis B, autoimmune hepatitis, Wilson's disease, or hemochromatosis.
- •Patients with mental disabilities, language barriers, poor social support or any other reason considered by the researcher as essential for adequate understanding, cooperation or compliance with the study.
- •Presence of data on alcoholic hepatitis in liver biopsy upon inclusion.
- •Patients with contraindications for statins.
- •Known hypersensitivity to simvastatin.
- •Refusal to sign the informed consent.
- •Patients in whom hepatitis C has been cured with antivirals in the 2 years prior to inclusion in the study.
- •Patients with a CK elevation of 50% or more above the upper limit of normal at the time of study inclusion
- •Gastrointestinal bleeding due to portal hypertension within the 12 months prior to inclusion in the study.
- •Clinical hepatic encephalopathy, defined as grade II-IV hepatic encephalopathy, in the 12 months prior to inclusion in the study.
- •Patients in need of diuretic treatment in the previous 6 months to control ascites or hydrothorax.
- •Spontaneous bacterial peritonitis within 12 months prior to study enrollment.
- •Patients with a Child-Pugh score > 8 points.
结局指标
主要结局
Change from baseline biopsy in the histological fibrosis score measured using the Ishak scale at 24 months.
Change from baseline biopsy in the histological fibrosis score measured using the Ishak scale at 24 months.
次要结局
- 1. Analyze the effect of simvastatin on liver fibrosis evaluated by noninvasive methods: a. Change in liver elasticity measured by transient liver elastography at 6, 12, 18 and 24 months. b. Change in liver elasticity measured by ERM at 24 months.
- 1.c. Changes in serum markers and liver fibrosis scores validated for ALD and widely used in the general population: FIB-4 (Fibrosis Index for Liver Fibrosis) and ELF (Enhanced liver Fibrosis), pro-collagen 3, hydroxyproline, metalloproteinase 1 and telopeptide, at 6, 12, 18 y 24 months.
- 2. Study the changes in liver fibrosis and other histological parameters of the disease: a. Absence of progression compared to the baseline biopsy in the histological fibrosis score measured using the Ishak scale at 24 months. b. Shift in the degree of liver fibrosis measured using the Ishak scale, estimated with ordinal analysis.
- 2.c. Changes in liver fibrosis evaluated using the Metavir scale (including the shift evaluated with ordinal analysis), the EPOS scale, and the "7-tier fibrosis staging system for ALD" at 24 months. d. Change in the collagen proportional area in liver biopsies stained with Sirius red and analyzed with Image J software at 24 months. e. Changes in histological parameters of chronic alcoholic liver disease: steatosis, neutrophil infiltration, Mallory bodies, etc., at 24 months.
- 3. Changes in the diversity and taxonomic composition of the gut microbiota through massive sequencing, at 24 months of treatment.
- 4. Analyze the markers of systemic inflammation, immune response, bacterial translocation, and endothelial dysfunction: a. Change in the levels of pro-inflammatory cytokines associated with alcoholic liver disease: IL-6, TNFα, and procalcitonin; at 6, 12, 18, and 24 months. b. Change in the levels of bacterial translocation markers: bacterial lipopolysaccharide and lipopolysaccharide-binding protein; at 6, 12, 18, and 24 months.
- 4.c. Change in the levels of endothelial dysfunction markers: nitric oxide (NO), von Willebrand factor (vWF); at 6, 12, 18, and 24 months. d. Change in the inflammatory profile of circulating immune cells: lymphocytes, monocytes, and neutrophils; at 24 months.
- 5. Analyze the polymorphisms of the SLCO1B1 gene and their relationship with muscle toxicity.
- 6. Incidence of adverse effects and safety of the treatment.
研究者
Dr. Pere Ginès
Scientific
Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer
研究点 (1)
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