Hepatoprotective Measures for Children at High Risk of NAFLD

NCT06918080 | Active Not Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: FMASU MD300/2023
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

Acute Lymphoblastic Leukemia; Obesity; NAFLD

Outcome Measures

Primary Outcomes (1)

• Study of the prevalence of liver steatosis, steatohepatitis and fibrosis among the study population by using LIVERFASt.

  Study of the prevalence of liver steatosis, steatohepatitis and fibrosis among the study population by using LIVERFASt.

  2 years

Secondary Outcomes (1)

• 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

Other Outcomes (1)

• To estimate the efficacy and safety of therapeutic interventions in the form of Omega-3 supplements, Ursodeoxycolic acid and life style changes by assessment of the side effects, and their efficacy on liver fibrosis, steatosis and steatohepatitis.

  2 years

Study Arms (2)

Arm (1)

EXPERIMENTAL

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.

Drug: Ursodeoxycholic Acid 250 Mg Oral Capsule; Dietary Supplement: Omega -3 fatty acids; Behavioral: Physical exercise; Behavioral: Mediterrenean diet

Arm(2)

ACTIVE COMPARATOR

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.

Behavioral: Diet according to NASPGHAN guidelines

Interventions

Ursodeoxycholic Acid 250 Mg Oral Capsule 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)

Arm (1)

Omega -3 fatty acids 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

Arm (1)

Physical exercise 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

Arm (1)

Mediterrenean diet 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 (1)

Diet according to NASPGHAN guidelines 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.

Arm(2)

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (2)

Ain Shams University

Cairo, 11566, Egypt

Location

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

Cairo, 11566, Egypt

Location

MeSH Terms

Conditions

Obesity; Overweight; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Non-alcoholic Fatty Liver Disease

Interventions

Ursodeoxycholic Acid; Docosahexaenoic Acids; Exercise

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes; Fatty Acids, Omega-3; Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Manal H El-Sayed, Professor of pediatrics

  Ain Shams University-Faculty of Medicine-Pediatric Department

  PRINCIPAL INVESTIGATOR

• Fatma SE Ebeid, Professor of pediatrics

  Ain Shams University-Faculty of Medicine-Pediatric Department

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2025
• First Posted: April 9, 2025
• Study Start: November 19, 2023
• Primary Completion: May 1, 2025
• Study Completion: July 1, 2025
• Last Updated: April 9, 2025

Record last verified: 2025-04

Locations

EG (2)