Hepatoprotective Measures for Children at High Risk of Non Alcoholic Fatty Liver Disease
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 200
- 试验地点
- 2
- 主要终点
- Study of the prevalence of liver steatosis, steatohepatitis and fibrosis among the study population by using LIVERFASt.
研究概览
简要总结
Non Alcoholic Fatty Liver Disease (NAFLD) is a spectrum of disease, ranging from simple fatty deposition (steatosis) to inflammation (steatohepatitis), fibrosis, cirrhosis, and end-stage liver failure. In childhood, it may be associated with a metabolic syndrome or with obesity, or even in normal children. Liver biopsy has always been the gold standard method for diagnosing and staging NAFLD. However, the urge of non-invasive biomarkers or imaging techniques has been recommended. This study will evaluate the use of the LIVERFASt biomarkers for early detection and staging of NAFLD.
详细描述
Nonalcoholic fatty liver disease (NAFLD), defined as abnormal hepatic accumulation of macrovesicular fat in the absence of other etiologies. NAFLD is becoming increasingly prevalent in the pediatric population in direct correlation with the emergence of childhood obesity as a significant pediatric health problem.
Most patients with NAFLD are asymptomatic, and the disease is detected incidentally. Some patients complain of fatigue, malaise, and vague right upper abdominal discomfort. The most common signs are hepatomegaly and laboratory abnormalities, which include a 2 to 4 fold elevation of serum aminotransferase levels, while other liver function test results are usually normal unless advanced liver disease is present. Most are obese, many have diabetes mellitus, hypercholesterolemia, or hypertriglyceridemia.
This study will recruit 195 children aged between 5-18 years divided in 3 groups, each 65 participants: (P1) overweighted (BMI between 84th& 94 th centiles) or obese (BMI>95th)and (P2) children on maintenance chemotherapy for acute lymphoblastic leukemia at risk for NAFLD, compared with control healthy children matched for gender and age (P3). Each participant will be subjected to history taking , clinical examination and anthropometric measures: weight,height,BMI,waist circumference and triceps skin fold thickness. Body composition will also be done.
Thereafter each participant will have a baseline LIVERFASt, U/S and Transient elastography assessments and will be randomly assigned by a computer based program to one of two interventional arms: Arm(1): which comprises Mediterranean Diet (MD) for 12 weeks, Supplementation of omega 3, the dose of omega-3 fatty acids will be determined by baseline weight (<40 kg-450 mg/day, 40-60 kg-900 mg/day, >60 kg-1300 mg/day), daily doses of Ursodeoxycholic acid (UCD)( Ursofalk) in a dose of 20 mg/Kg/day in two divided doses depending on their body weight for 12 weeks and a 12-week exercise program for 30-45 min/day for 3 days/week. in the first two weeks and for 60 min/day for 4-5 days/week in the following weeks. In Arm(2), Patients will receive lifestyle modification according to NASPGHAN Clinical Guidelines for the treatment of NAFLD in Children. Patients will follow healthy and well-balanced diet. Patient caloric intake will be calculated according to the Recommended Daily Allowance (RDA) for age ) with avoidance of sugar-sweetened beverages, moderate- to high-intensity exercise daily will be encouraged, and screen time will be limited to less than 2 hours. The group of patients on chemothrapy will all receive arm(1) intervention without randomization,so as not to deprive them from the hypothecal benefit of the intervention.
LIVERFASt evaluation and imaging will be repeated by the end of the 12 week intervention period as follow up
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Children aged between 5-18 years, including:
- •Population P1: N=65 overweight (BMI between 85th & 94th centile) and obese children (BMI = or > 95th centile) at-risk of NAFLD
- •Population P2: N=65 children on maintenance therapy (High Dose Methotrexate 2.5 or 5 mg according to risk level, every other week for 4 doses and daily 6-Mercaptopurine tab. 50 mg/m2/day for 56 days) for Acute Lymphoblastic Leukemia, at risk of chemotherapy induced steatohepatitis.
- •Population P3: N=65 control healthy children matched for gender and age with P1&2.
排除标准
- •Conditions that could interfere with measured labs (acute/chronic hemolysis, acute hepatitis, extra hepatic cholestasis, systemic inflammatory response).
研究组 & 干预措施
Arm (1)
Patients will follow Mediterranean Diet (MD) for 12 weeks, this diet is characterized by a high intake of vegetables, fruit, whole cereals, legumes, nuts, and fish and a low intake of red meat and homemade desserts. The main added fat is extra virgin olive oil, with 35-40% kcal from fat (<10% from saturated fat), 40-44% kcal from carbohydrate, and 20% kcal from protein. Patient caloric intake will be calculated according to the Recommended Daily Allowance (RDA) for age.
Supplementation of omega 3, the dose of omega-3 fatty acids will be determined by baseline weight (<40 kg-450 mg/day, 40-60 kg-900 mg/day, >60 kg-1300 mg/day).
Patients will also receive daily doses of Ursodeoxycholic acid (UCD) Ursofalk) in a dose of 20 mg/Kg/day in two divided doses depending on their body weight for 12 weeks. Patients will participate in a 12-week exercise program for 30-45 min/day for 3 days/week in the first 2 weeks and for 60 min/day for 4-5 days/week thereafter.
干预措施: Ursodeoxycholic Acid 250 Mg Oral Capsule (Drug)
Arm (1)
Patients will follow Mediterranean Diet (MD) for 12 weeks, this diet is characterized by a high intake of vegetables, fruit, whole cereals, legumes, nuts, and fish and a low intake of red meat and homemade desserts. The main added fat is extra virgin olive oil, with 35-40% kcal from fat (<10% from saturated fat), 40-44% kcal from carbohydrate, and 20% kcal from protein. Patient caloric intake will be calculated according to the Recommended Daily Allowance (RDA) for age.
Supplementation of omega 3, the dose of omega-3 fatty acids will be determined by baseline weight (<40 kg-450 mg/day, 40-60 kg-900 mg/day, >60 kg-1300 mg/day).
Patients will also receive daily doses of Ursodeoxycholic acid (UCD) Ursofalk) in a dose of 20 mg/Kg/day in two divided doses depending on their body weight for 12 weeks. Patients will participate in a 12-week exercise program for 30-45 min/day for 3 days/week in the first 2 weeks and for 60 min/day for 4-5 days/week thereafter.
干预措施: Omega -3 fatty acids (Dietary Supplement)
Arm (1)
Patients will follow Mediterranean Diet (MD) for 12 weeks, this diet is characterized by a high intake of vegetables, fruit, whole cereals, legumes, nuts, and fish and a low intake of red meat and homemade desserts. The main added fat is extra virgin olive oil, with 35-40% kcal from fat (<10% from saturated fat), 40-44% kcal from carbohydrate, and 20% kcal from protein. Patient caloric intake will be calculated according to the Recommended Daily Allowance (RDA) for age.
Supplementation of omega 3, the dose of omega-3 fatty acids will be determined by baseline weight (<40 kg-450 mg/day, 40-60 kg-900 mg/day, >60 kg-1300 mg/day).
Patients will also receive daily doses of Ursodeoxycholic acid (UCD) Ursofalk) in a dose of 20 mg/Kg/day in two divided doses depending on their body weight for 12 weeks. Patients will participate in a 12-week exercise program for 30-45 min/day for 3 days/week in the first 2 weeks and for 60 min/day for 4-5 days/week thereafter.
干预措施: Physical exercise (Behavioral)
Arm (1)
Patients will follow Mediterranean Diet (MD) for 12 weeks, this diet is characterized by a high intake of vegetables, fruit, whole cereals, legumes, nuts, and fish and a low intake of red meat and homemade desserts. The main added fat is extra virgin olive oil, with 35-40% kcal from fat (<10% from saturated fat), 40-44% kcal from carbohydrate, and 20% kcal from protein. Patient caloric intake will be calculated according to the Recommended Daily Allowance (RDA) for age.
Supplementation of omega 3, the dose of omega-3 fatty acids will be determined by baseline weight (<40 kg-450 mg/day, 40-60 kg-900 mg/day, >60 kg-1300 mg/day).
Patients will also receive daily doses of Ursodeoxycholic acid (UCD) Ursofalk) in a dose of 20 mg/Kg/day in two divided doses depending on their body weight for 12 weeks. Patients will participate in a 12-week exercise program for 30-45 min/day for 3 days/week in the first 2 weeks and for 60 min/day for 4-5 days/week thereafter.
干预措施: Mediterrenean diet (Behavioral)
Arm(2)
Patients will receive lifestyle modification according to NASPGHAN Clinical Guidelines for the treatment of NAFLD in Children. Patients will follow healthy and well-balanced diet. Patient caloric intake will be calculated according to the Recommended Daily Allowance (RDA) for age with avoidance of sugar-sweetened beverages, moderate- to high-intensity exercise daily will be encouraged, and screen time will be limited to less than 2 hours.
干预措施: Diet according to NASPGHAN guidelines (Behavioral)
结局指标
主要结局
Study of the prevalence of liver steatosis, steatohepatitis and fibrosis among the study population by using LIVERFASt.
时间窗: 2 years
Study of the prevalence of liver steatosis, steatohepatitis and fibrosis among the study population by using LIVERFASt.
次要结局
- To compare the prevalence of NAFLD as estimated by LIVERFASt ,in two paediatric populations: who use chemotherapy for hematologic malignancies, and other who are at high risk of NAFLD(obese and overweighted)with apparently healthy controls matched for ge(2 years)