NCT01265498已完成2 期
The Farnesoid X Receptor (FXR) Ligand Obeticholic Acid in Nonalcoholic Steatohepatitis (NASH) Treatment (FLINT) Trial
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)9 个研究点 分布在 1 个国家目标入组 283 人开始时间: 2011年3月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 283
- 试验地点
- 9
- 主要终点
- Hepatic Histological Improvement in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)
研究概览
简要总结
Administration of the farnesoid X receptor (FXR) ligand obeticholic acid (OCA) for 72 weeks to subjects with biopsy evidence of nonalcoholic steatohepatitis (NASH) will result in improvement in their liver disease as measured by changes in the nonalcoholic fatty liver disease (NAFLD) activity score (NAS).
详细描述
To evaluate whether treatment with obeticholic acid, 25 mg daily for 72 weeks compared to treatment with placebo, improves the severity of nonalcoholic fatty liver disease (NAFLD) as determined from hepatic histology.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years of age or older as of the initial screening interview and provision of consent
- •Histologic evidence of definite or probable nonalcoholic steatohepatitis (NASH) based upon a liver biopsy obtained no more than 90 days prior to randomization and a nonalcoholic fatty liver disease activity score (NAS) of 4 or greater with at least 1 in each component of the NAS score (steatosis scored 0-3, ballooning degeneration scored 0-2, and lobular inflammation scored 0-3).
排除标准
- •Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening (significant alcohol consumption is defined as more than 20 grams per day in females and more than 30 grams per day in males, on average)
- •Inability to reliably quantify alcohol consumption based upon local study physician judgment
- •Use of drugs historically associated with nonalcoholic fatty liver disease (NAFLD) (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, valproic acid, and other known hepatotoxins) for more than 2 weeks in the year prior to randomization
- •Prior or planned (during the study period) bariatric surgery (eg, gastroplasty, roux-en-Y gastric bypass)
- •Uncontrolled diabetes defined as Hemoglobin A1c 9.5% or higher within 60 days prior to enrollment
- •Presence of cirrhosis on liver biopsy
- •A platelet count below 100,000/mm3
- •Clinical evidence of hepatic decompensation as defined by the presence of any of the following abnormalities:
- •Serum albumin less than 3.2 grams/deciliter (g/dL)
- •International Normalized Ratio(INR)greater than 1.3
- •Direct bilirubin greater than 1.3 milligrams per deciliter (mg/dL)
- •History of esophageal varices, ascites or hepatic encephalopathy
- •Evidence of other forms of chronic liver disease:
- •Hepatitis B as defined by presence of hepatitis B surface antigen (HBsAg)
- •Hepatitis C as defined by presence of hepatitis C virus (HCV) ribonucleic acid (RNA) or positive hepatitis C antibody (anti-HCV)
- •Evidence of ongoing autoimmune liver disease as defined by compatible liver histology
- •Primary biliary cirrhosis as defined by the presence of at least 2 of these criteria (i) Biochemical evidence of cholestasis based mainly on alkaline phosphatase elevation (ii)Presence of anti-mitochondrial antibody (AMA) (iii)Histologic evidence of nonsuppurative destructive cholangitis and destruction of interlobular bile ducts
- •Primary sclerosing cholangitis
- •Wilson's disease as defined by ceruloplasmin below the limits of normal and compatible liver histology
- •Alpha-1-antitrypsin(A1AT) deficiency as defined by diagnostic features in liver histology (confirmed by alpha-1 antitrypsin level less than normal; exclusion at the discretion of the study physician)
- •History of hemochromatosis or iron overload as defined by presence of 3+ or 4+ stainable iron on liver biopsy
- •Drug-induced liver disease as defined on the basis of typical exposure and history
- •Known bile duct obstruction
- •Suspected or proven liver cancer
- •Any other type of liver disease other than nonalcoholic steatohepatitis (NASH)
- •Serum alanine aminotransferase (ALT) greater than 300 units per liter (U/L)
- •Serum creatinine of 2.0 mg/dL or greater
- •Use of ursodeoxycholic acid (Ursodiol, Urso) within 90 days prior to enrollment
- •Inability to safely obtain a liver biopsy
- •History of biliary diversion
- •Known positivity for Human Immunodeficiency Virus (HIV) infection
- •Active, serious medical disease with likely life expectancy less than 5 years
- •Active substance abuse including inhaled or injection drugs in the year prior to screening
- •Pregnancy, planned pregnancy, potential for pregnancy and unwillingness to use effective birth control during the trial, breast feeding
- •Participation in an investigational new drug (IND) trial in the 30 days before randomization
- •Any other condition which, in the opinion of the investigator, would impede compliance or hinder completion of the study
- •Failure to give informed consent
研究组 & 干预措施
Obeticholic acid
Active Comparator
obeticholic acid
干预措施: obeticholic acid (Drug)
Placebo
Placebo Comparator
Placebo
干预措施: placebo (Drug)
结局指标
主要结局
Hepatic Histological Improvement in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)
时间窗: baseline to 72 weeks
Centrally scored histological improvement in nonalcoholic fatty liver disease (NAFLD) from baseline to the end of 72 weeks of treatment, where improvement is defined as: 1. No worsening in fibrosis; and 2. A decrease in NAFLD Activity Score (NAS) of at least 2 points
次要结局
- Change in Bicarbonate(baseline to 72 weeks)
- Change in Calcium(baseline to 72 weeks)
- Change in Phosphate(baseline to 72 weeks)
- Change in Creatinine(baseline to 72 weeks)
- Change in Uric Acid(baseline to 72 weeks)
- Change in Albumin(baseline to 72 weeks)
- Change in Total Protein(baseline to 72 weeks)
- Change in Prothrombin Time(baseline to 72 weeks)
- Change in International Normalised Ratio(baseline to 72 weeks)
- Change in Fasting Serum Glucose(baseline to 72 weeks)
- Change in Insulin(baseline to 72 weeks)
- Change in HOMA-IR(baseline to 72 weeks)
- Change in Glycated Haemoglobin A1c(baseline to 72 weeks)
- Change in Weight(baseline to 72 weeks)
- Change in Body-mass Index(baseline to 72 weeks)
- Change in Waist Circumference(baseline to 72 weeks)
- Change in Waist-to-hip Ratio(baseline to 72 weeks)
- Change in Systolic Blood Pressure(baseline to 72 weeks)
- Change in Diastolic Blood Pressure(baseline to 72 weeks)
- Change in Haematocrit(baseline to 72 weeks)
- Change in Mean Corpuscular Volume(baseline to 72 weeks)
- Change in White Blood Cell Count(baseline to 72 weeks)
- Steatosis: Patients With Improvement(baseline to 72 weeks)
- Change in Platelet Count(baseline to 72 weeks)
- Resolution of NASH Diagnosis(baseline to 72 weeks)
- Fibrosis: Patient With Improvement(baseline to 72 weeks)
- Fibrosis: Change in Score(baseline to 72 weeks)
- Total NAFLD Activity Score: Change in Score(baseline to 72 weeks)
- Hepatocellular Ballooning: Patients With Improvement(baseline to 72 weeks)
- Hepatocellular Ballooning: Change in Score(baseline to 72 weeks)
- Steatosis: Change in Score(baseline to 72 weeks)
- Lobular Inflammation: Patients With Improvement(baseline to 72 weeks)
- Lobular Inflammation: Change in Score(baseline to 72 weeks)
- Portal Inflammation: Patients With Improvement(baseline to 72 weeks)
- Portal Inflammation: Change in Score(baseline to 72 weeks)
- Change in Alanine Aminotransferase(baseline to 72 weeks)
- Change in Asparate Aminotransferase(baseline to 72 weeks)
- Change in Alkaline Phosphatase(baseline to 72 weeks)
- Change in γ-glutamyl Transpeptidase(baseline to 72 weeks)
- Change in Total Bilirubin(baseline to 72 weeks)
- Change in Total Cholesterol(baseline to 72 weeks)
- Change in HDL Cholesterol(baseline to 72 weeks)
- Change in LDL Cholesterol(baseline to 72 weeks)
- Change in Triglycerides(baseline to 72 weeks)
- Change in Haemoglobin(baseline to 72 weeks)
- Change in SF-36 Quality of Life Physical Component Summary(baseline to 72 weeks)
- Change in SF-36 Quality of Life Mental Component Summary(baseline to 72 weeks)
研究者
研究点 (9)
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