NCT03467217终止2 期
Losartan for the Treatment of Pediatric NAFLD (STOP-NAFLD): A Phase 2, Randomized, Placebo-Controlled Clinical Trial
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)10 个研究点 分布在 1 个国家目标入组 83 人开始时间: 2018年10月2日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 83
- 试验地点
- 10
- 主要终点
- Change in Serum Alanine Aminotransferase (ALT) From Baseline.
研究概览
简要总结
A multicenter, randomized, double masked, placebo-controlled, parallel treatment groups phase 2 trial of losartan for pediatric nonalcoholic fatty liver disease (NAFLD).
详细描述
Children ages 8-17 years weighing between 70 -149 kilograms will be enrolled and treated with losartan (100 mg orally once per day) or matching placebo for 24 weeks. The hypothesis is that losartan will improve serum alanine aminotransferase (ALT) in children with pediatric NAFLD.
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)
盲法说明
Participants, investigators, clinical staff, and data monitoring committee will not have knowledge of the interventions assigned to individual participants.
入排标准
- 年龄范围
- 8 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 8-17 years at initial screening interview
- •Histological evidence of NAFLD with or without fibrosis and a NAFLD activity score (NAS) of ≥3, on a liver biopsy obtained no more than 730 days prior to enrollment.
- •Serum ALT at screening ≥ 50 IU/L
排除标准
- •Body weight less than 70 kg or greater than 150 kg at screening
- •Significant alcohol consumption or inability to reliably quantify alcohol intake
- •Use of drugs historically associated with NAFLD (amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, valproic acid, other known hepatotoxins) for more than 2 consecutive weeks in the past year prior to randomization
- •New treatment with vitamin E or metformin started in the past 90 days or plans to alter the dose or stop over the next the 24 weeks. A stable dose is acceptable.
- •Prior or planned bariatric surgery
- •Uncontrolled diabetes (HbA1c 9.5% or higher)
- •Presence of cirrhosis on liver biopsy
- •History of hypotension or history of orthostatic hypotension
- •Stage 2 Hypertension or >140 systolic or >90 diastolic at screening
- •Current treatment with any antihypertensive medications including all angiotensin converting enzyme (ACE) inhibitors or aliskiren
- •Current treatment with potassium supplements or any drug known to increase potassium
- •Current daily use of nonsteroidal anti-inflammatory drugs (NSAIDs)
- •Current treatment with lithium
- •Platelet counts below 100,000 /mm3
- •Clinical evidence of hepatic decompensation (serum albumin < 3.2 g/dL, international normalized ratio (INR) >1.3, direct bilirubin >1.3 mg/dL, history of esophageal varices, ascites, or hepatic encephalopathy)
- •Evidence of chronic liver disease other than NAFLD:
- •Biopsy consistent with histological evidence of autoimmune hepatitis
- •Serum hepatitis B surface antigen (HBsAg) positive.
- •Serum hepatitis C antibody (anti-HCV) positive.
- •Iron/total iron binding capacity (TIBC) ratio (transferrin saturation) > 45% with histological evidence of iron overload
- •Alpha-1-antitrypsin (A1AT) phenotype/genotype ZZ or SZ
- •Wilson's disease
- •Serum alanine aminotransferase (ALT) greater than 300 IU/L
- •History of biliary diversion
- •History of kidney disease and/or estimated glomerular filtration rate (eGFR) < than 60 mL/min/1.73 m2 using Schwartz Bedside GFR Calculator for Children isotope dilution mass spectroscopy (IDMS)-traceable
- •Known Human Immunodeficiency Virus (HIV) infection
- •Active, serious medical disease with life expectancy less than 5 years
- •Active substance abuse including inhaled or injected 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 150 days prior to randomization
- •Any other condition which, in the opinion of the investigator, would impede compliance or hinder completion of the study
- •Inability to swallow capsules
- •Known allergy to losartan potassium or other angiotensin receptor blocker
- •Failure of parent or legal guardian to give informed consent or subject to give informed assent
研究组 & 干预措施
Losartan potassium capsule
Active Comparator
Dose will be one 50 mg capsule of losartan per day for one week and then increased to two capsules of 50 mg of losartan per day (100 mg total) for 23 weeks patients with baseline weight ≥ 70 kg to <150 kg.
干预措施: Losartan potassium (Drug)
Placebo losartan capsule
Placebo Comparator
Dose will be one 50 mg capsule of placebo losartan per day for one week and then increased to two capsules of 50 mg of placebo losartan per day (100 mg total) for 23 weeks for patients with baseline weight ≥ 70 kg to <150 kg.
干预措施: Placebo losartan capsule (Drug)
结局指标
主要结局
Change in Serum Alanine Aminotransferase (ALT) From Baseline.
时间窗: Baseline and 24 weeks
Change ALT value in U/L (24 weeks minus baseline). A negative score indicates improvement.
次要结局
- Change in Gamma-glutamyl Transpeptidase (GGT) Compared to Baseline(Baseline and 24 weeks)
- Change in Serum Aspartate Aminotransferase AST at 24 Weeks Compared to Baseline AST(Baseline and 24 weeks)
- Relative Change in Serum Alanine Aminotransferase (ALT) Compared to Baseline ALT(Baseline and 24 weeks)
- Change in ALT at 12 Weeks Compared to Baseline ALT(Baseline and 12 weeks)
- Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Compared to Baseline.(Baseline and 24 weeks)
- Change in Weight at 24 Weeks Compared to Baseline(Baseline and 24 weeks)
- Change in Body Mass Index (BMI) at 24 Weeks Compared to Baseline.(Baseline and 24 weeks)
- Change in Waist Circumference at 24 Weeks Compared to Baseline(Baseline and 24 weeks)
- Change in Waist-to-hip Ratio at 24 Weeks Compared to Baseline(Baseline and 24 weeks)
- Change in Pediatric Quality of Life Inventory (PedsQOL) Physical Health Score at 24 Weeks Compared to Baseline(Baseline and 24 weeks)
- Frequency of Adverse Events Over 24 Weeks(Baseline and 24 weeks)
- Change in Total Cholesterol at 24 Weeks Compared to Baseline(Baseline and 24 weeks)
- Change in Triglycerides at 24 Weeks Compared to Baseline(Baseline and 24 weeks)
- Change in HDL Cholesterol at 24 Weeks Compared to Baseline(Baseline and 24 weeks)
- Change in LDL Cholesterol at 24 Weeks Compared to Baseline(Baseline and 24 weeks)
- Change in Pediatric Quality of Life Inventory (PedsQOL) Psychosocial Health Score at 24 Weeks Compared to Baseline(Baseline and 24 weeks)
研究者
研究点 (10)
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