Hepatoprotective Measures for Children at High Risk of NAFLD

NCT ID: NCT06918080

Last Updated: 2025-04-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-19
• Study Completion Date: 2025-07-31

Brief Summary

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.

Detailed Description

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

Screening for NAFLD is appropriate because it can be detected before the onset of irreversible, end-stage liver disease. Identification of children with NAFLD is important because effective treatment is available. Although more challenging to implement than prescribing a medication, lifestyle intervention can be effective at reversing NAFLD and even NASH, particularly if initiated early in the course of disease, before advanced fibrosis has developed.

Although liver biopsy is the current standard to provide critical diagnostic and staging information, including the presence of NASH, and to eliminate alternative and/or concurrent diagnoses. Liver biopsy has inherent limitations for staging NAFLD because of the non uniformity of disease throughout the liver in reference to the small sample of liver obtained Other noninvasive methods used as screening tests for NAFLD include measurement of liver stiffness through transient elastography, which is an accurate and reproducible methodology to identify pediatric subjects without fibrosis or significant fibrosis, or with advanced fibrosis.

LIVERFASt (LF)is a panel of three non-invasive patented artificial intelligence neural networks algorithms estimating liver fibrosis (LF-Fib), inflammatory activity (LF-Act) and steatosis (LF-Ste) intended for the evaluation of NAFLD risk patients. It combines age, gender and BMI with ten serum biomarkers easy to determine in routine biochemistry in fasting patients that are independently correlated with the severity of each histological feature of nonalcoholic fatty liver disease (NAFLD).

This study evaluates the use of the LIVERFASt biomarkers as well as ultrasound (US) for early detection and staging of NAFLD, and the impact of a designed non-invasive therapeutic intervention in the form of Omega-3, Ursodeoxycholic acid and lifestyle modification, in 2 groups of children compared with a control group of healthy children age and gender matched.

Conditions

Non Alcoholic Fatty Liver Diseases (NAFLD); Obesity and Overweight; Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Ursodeoxycholic Acid 250 Mg Oral Capsule

Intervention Type: DRUG

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 will be assigned to arm(1)

Omega -3 fatty acids

Intervention Type: DIETARY_SUPPLEMENT

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) will be assigned to children in arm (1). Side effect such as gastrointestinal upset and allergy will be monitored, compliance will be monitored by weekly phone call

Physical exercise

Intervention Type: BEHAVIORAL

Patients assigned to arm (1) will participate in 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

Mediterrenean diet

Intervention Type: BEHAVIORAL

Patients in arm (1) 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.( Plaz et al., 2019) Patient caloric intake will be calculated according to the Recommended Daily Allowance (RDA) for age.

Compliance to the MD will be assessed in all patients using the KIDMED index at 4 ,8 and 12 weeks.Those who prove to be non-compliant will be excluded from the study.

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.

Group Type: ACTIVE_COMPARATOR

Diet according to NASPGHAN guidelines

Intervention Type: BEHAVIORAL

Patients in arm (2) 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.

Interventions

Ursodeoxycholic Acid 250 Mg Oral Capsule

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 will be assigned to arm(1)

Intervention Type: DRUG

Omega -3 fatty acids

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) will be assigned to children in arm (1). Side effect such as gastrointestinal upset and allergy will be monitored, compliance will be monitored by weekly phone call

Intervention Type: DIETARY_SUPPLEMENT

Physical exercise

Patients assigned to arm (1) will participate in 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

Intervention Type: BEHAVIORAL

Mediterrenean diet

Patients in arm (1) 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.( Plaz et al., 2019) Patient caloric intake will be calculated according to the Recommended Daily Allowance (RDA) for age.

Compliance to the MD will be assessed in all patients using the KIDMED index at 4 ,8 and 12 weeks.Those who prove to be non-compliant will be excluded from the study.

Intervention Type: BEHAVIORAL

Diet according to NASPGHAN guidelines

Patients in arm (2) 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.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

• Conditions that could interfere with measured labs (acute/chronic hemolysis, acute hepatitis, extra hepatic cholestasis, systemic inflammatory response).

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Manal H El-Sayed, Professor of pediatrics

Role: PRINCIPAL_INVESTIGATOR

Ain Shams University-Faculty of Medicine-Pediatric Department

Fatma SE Ebeid, Professor of pediatrics

Role: STUDY_CHAIR

Ain Shams University-Faculty of Medicine-Pediatric Department

Locations

Ain Shams University

Cairo, , Egypt

Faculty of Medicine Ain Shams Research Institute- Clinical Research Center (MASRI-CRC)

Cairo, , Egypt

Countries

Egypt

Other Identifiers

FMASU MD300/2023

Identifier Type: OTHER

Identifier Source: secondary_id

FMASU MD300/2023

Identifier Type: -

Identifier Source: org_study_id