Hydroxytyrosol and Vitamin E in the Treatment of Children With Biopsy-proven NASH
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Improvement of laboratory markers of inflammation and oxidative stress, such as concentrations of TNF-alpha, lipopolysaccharide (LPS), adiponectin, catepsin D, cytokeratin-18.
研究概览
简要总结
Non-alcoholic fatty liver disease (NAFLD) has reached epidemic proportions and is rapidly becoming the one of most common causes of chronic liver disease in children. The pathogenesis of NAFLD is generally considered the result of a series of liver injuries, commonly referred as "multi-hit" hypothesis. Several studies suggest that inflammatory pathways and oxidative stress could be responsible of disease progression to non-alcoholic steatohepatitis (NASH).
Hydroxytyrosol is a simple phenolic compound naturally occurring in olive and olive oil with antioxidant properties. Some studies have demonstrated that hydroxytyrosol show several anti-inflammatory and anti-atherogenic activities, such as the inhibition of LDL oxidation and platelet aggregation.
Alpha tocopherol (Vitamin E) is the most studied anti-oxydant in pediatric NAFLD with conflicting results. It inhibits proinflammatory cytokine production and attenuates the release of profibrogenic agents and liver collagen.
The purpose of this interventional study is to evaluate the efficacy and tolerability of Hydroxytyrosol and Vitamin E in the treatment of children with biopsy-proven NASH.
详细描述
80 children and adolescents (4-16 years) with biopsy-proven NASH will be enrolled. They will be randomized to treatment with hydroxytyrosol and vitamin E (n: 40 pts) or an identical placebo (n: 40 pts) given orally for a period of 16 weeks. Patients will undergo a medical evaluation at baseline (enrollment) and after 4 months (end of treatment). Anthropometric measures and laboratory assay, includin liver enzymes, gluco-insulinemic and lipid profiles will be performed at baseline and at the end of the study. Hepatic ultrasound examination will be performed at enrollment and at the end of the study.
Serum sample for determination of markers of inflammation and oxidative stress will be collected at enrollment and at the end of the study.
A stool sample for analysis of gut microbioma will be collected at enrollment and at the end of the study.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 4 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Liver biopsy consistent with diagnosis of NASH (liver biopsy performed in 3-6 months before enrollment)
- •Hyperechogenicity of liver at ultrasound examination
- •ALT levels range between normal and < 10 UNL
- •INR < 1.3
- •Albumin > 3 gr/dl.
- •Total bilirubin < 2.5 mg/dl
- •normal renal function
- •normal cells blood count
- •exclusion of other causes of chronic hepatopathies in children
- •Written informed consent to participate in the Protocol by their parents or legal guardians of patients
排除标准
- •alcohols or drugs abuse
- •use of drugs known to induce steatosis or to affect body weight or carbohydrate metabolism
- •autoimmune liver diseases, Wilson's disease, alpha-1-antitripsin deficiency, metabolic liver disease
- •every clinical or psychiatric diseases interfering with experimentation according to investigator's evaluation
- •finding of active liver disease due to other causes
研究组 & 干预措施
TREATED GROUP
This group will treated with 2 pills daily, each containing 3.75 mg of hydroxytyrosol plus 5 mg of Vitamin E, given orally for 16 weeks.
干预措施: Hydroxytyrosol plus Vitamin E (Drug)
PLACEBO GROUP
This group will treated with 2 identical placebo pills daily given orally for 16 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Improvement of laboratory markers of inflammation and oxidative stress, such as concentrations of TNF-alpha, lipopolysaccharide (LPS), adiponectin, catepsin D, cytokeratin-18.
时间窗: 4 months
Improvement of laboratory parameters of metabolic syndrome, such as lipids and gluco-insulinemic profile, transaminases serum levels
时间窗: 4 months
次要结局
- Number of participants with treatment-related adverse events as assessed by CTCAE(4 months)
- Analysis of fecal gut microbiome of patients before and after treatment with hydroxytyrosol and vitamin E(4 months)
- Improvement of echographic score of hepatic steatosis (echographic scale)(4 months)
研究者
Valerio Nobili
Professor
Bambino Gesù Hospital and Research Institute