Effects of Docosahexaenoic Acid (DHA) on Children With Nonalcoholic Fatty Liver Disease (NAFLD)

Study Overview
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Brief Summary
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The purpose of this interventional study is to evaluate the efficacy and tolerability of docosahexaenoic acid (DHA) in children or adolescents with well-characterized and liver biopsy confirmed nonalcoholic fatty liver disease (NAFLD).

Detailed Description
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Sixty children or adolescents (4-16 years) with liver biopsy proven NAFLD will be enrolled. They will be randomized to treatment with DHA 250 mg/kg/d (n=20), DHA 500 mg/kg/d (n=20), or an identical placebo (n=20) given orally for a period of 24 months. All patients will be included in a lifestyle intervention program consisting of a diet tailored on the individual requirements and physical exercise. Patients will undergo a medical evaluation every three months during the 24-month study period. Liver biopsy will be performed only at baseline and at the end of treatment. Anthropometric analysis, laboratory tests, including liver enzymes and lipids will be repeated at 3-month intervals during the 24-month study duration. Ultrasonography and Fibroscan of the liver will be repeated at the end of the study period.

Official Title
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Study of Efficacy and Tolerability of Docosahexaenoic Acid (DHA) on Children Affected by Nonalcoholic Fatty Liver Disease (NAFLD).

Conditions
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Fatty Liver, Liver Fibrosis, Obesity, Metabolic Syndrome, Nonalcoholic Fatty Liver Disease

Intervention / Treatment
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* Drug: DHA250
* Drug: DHA500
* Drug: PLACEBO
* Behavioral: Lifestyle intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: persistently elevated serum aminotransferase levels diffusely echogenic liver on imaging studies suggestive of fatty liver biopsy consistent with the diagnosis of NAFLD Exclusion Criteria: hepatic virus infections (HCV RNA-PCR negative) Hepatitis A, B, C, D, E and G cytomegalovirus and Epstein-Barr virus alcohol consumption history of parenteral nutrition use of drugs known to induce steatosis or to affect body weight and carbohydrate metabolism autoimmune liver disease, metabolic liver disease, Wilson's disease, and a-1-antitrypsin-associated liver disease were ruled out using standard clinical, laboratory and histological criteria

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DHA250<br>DHA 250 mg/kg/d plus lifestyle intervention [hypocaloric Diet (25-30 cal/kg/d) or isocaloric (40-45 cal/kg/d) and physical activity]. | Drug: DHA250<br>* DHA 250 mg/kg/d<br>* Other names: Docosahexaenoic Acid;Behavioral: Lifestyle intervention<br>* lifestyle intervention [including hypocaloric diet (25-30 cal/kg/d) or isocaloric diet (40-45 cal/kg/d) and physical activity], for 12 months.<br>* Other names: Diet and physical activity;|
| Experimental: DHA500<br>DHA 250 mg/kg/d plus lifestyle intervention [hypocaloric Diet (25-30 cal/kg/d) or isocaloric (40-45 cal/kg/d) and physical activity]. | Drug: DHA500<br>* DHA 500 mg/kg/d<br>* Other names: Docosahexaenoic Acid;Behavioral: Lifestyle intervention<br>* lifestyle intervention [including hypocaloric diet (25-30 cal/kg/d) or isocaloric diet (40-45 cal/kg/d) and physical activity], for 12 months.<br>* Other names: Diet and physical activity;|
| Placebo Comparator: PLA<br>placebo and lifestyle intervention [hypocaloric Diet (25-30 cal/kg/d) or isocaloric (40-45 cal/kg/d) and physical activity]. | Drug: PLACEBO<br>* placebo<br>* Other names: No interventions;Behavioral: Lifestyle intervention<br>* lifestyle intervention [including hypocaloric diet (25-30 cal/kg/d) or isocaloric diet (40-45 cal/kg/d) and physical activity], for 12 months.<br>* Other names: Diet and physical activity;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver status by liver biopsy (steatosis and fibrosis) |  | months 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum alanine transferase levels |  | month 24 | 
| Serum levels of triglycerides |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NAFLD, NASH, fibrosis