Curcumin for Pediatric Nonalcoholic Fatty Liver Disease: A Pilot Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Change in serum alanine aminotransferase (ALT) from baseline.
研究概览
简要总结
This is a single-center, randomized, double-blinded, placebo-controlled, parallel treatment groups phase 2a study of curcumin for pediatric nonalcoholic fatty liver disease (NAFLD).
详细描述
30 subjects ages 8-17y, with biopsy-proven NASH/NAFLD (≤ 730 days prior to registration and a NAFLD Activity Score (NAS) of ≥3) and serum ALT at screening ≥ 50 IU/L at enrollment. Eligible participants will receive curcumin 500 mg, 1.0 g or placebo for 24 weeks, randomized 1:1:1. The primary outcome of the study will determine whether 24 weeks of curcumin supplementation compared to matching placebo improves measures of nonalcoholic fatty liver disease (NAFLD) as determined by relative improvement in serum ALT from baseline. The hypothesis is that curcumin will significantly decrease ALT relative to placebo in children with 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
- •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 within 30 days prior to enrollment)
- •Presence of cirrhosis on liver biopsy
- •Stage 2 Hypertension or >140 systolic or >90 diastolic at screening
- •Current daily use of nonsteroidal anti-inflammatory drugs (NSAIDs)
- •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
- •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 any clinical/investigational trial within the prior 150 days and during the study.
- •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 curcumin or any of its components
- •Failure of parent or legal guardian to give informed consent or subject to give informed assent
研究组 & 干预措施
Curcumin 500mg capsules
Dose will be 500mg daily phosphatidylcholine-curcumin complex supplement, orally for 24 weeks
干预措施: phosphatidylcholine-curcumin complex supplement (Drug)
Curcumin 1000mg capsules
Dose will be1g daily of phosphatidylcholine-curcumin complex supplement, orally for 24 weeks
干预措施: phosphatidylcholine-curcumin complex supplement (Drug)
Placebo curcumin capsules
Dose will be matching placebo capsules daily, orally for 24 weeks
干预措施: Placebo curcumin capsule (Drug)
结局指标
主要结局
Change in serum alanine aminotransferase (ALT) from baseline.
时间窗: 24 weeks
ALT value in U/L
次要结局
- Relative change in ALT compared to baseline ALT(24 weeks)
- Change in serum aspartate aminotransferase (AST)(24 weeks)
- Change in ALT at 12 weeks compared to baseline ALT(12 weeks)
- Change in Waist circumference(24 weeks)
- Change in serum gamma-glutamyl transpeptidase (GGT)(24 weeks)
- Change in Weight(24 weeks)
- Change in Body-mass Index Z- Score(24 weeks)
- Proportion of patients achieving normalization of ALT(24 weeks)
- Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) compared to baseline(24 weeks)
- Change in High Sensitivity C-Reactive Protein (hsCRP) compared to baseline(24 weeks)
- Change in Waist to Hip ratio(24 weeks)
- Change in Pediatric Quality of Life Inventory (PedsQL) Score scores compared to baseline(24 weeks)
- Change in Intrahepatic fat content and liver stiffness(24 weeks)
- Change in frequency of adverse events compared to baseline(24 weeks)
- Change in serum lipids compared to baseline(24 weeks)