DHA and Vitamin D in Children With Biopsy-proven NAFLD

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

Detailed Description
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Sixty-six children or adolescents (4-16 years) with liver biopsy proven NAFLD will be enrolled. They will be randomized to treatment with DHA and Vitamin D (n=33) or an identical placebo (n=33) given orally for a period of 6 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 at 3-6 and 12 months during the 12-months study period. Liver biopsy will be performed at baseline and at 12 months. Anthropometric measurements and laboratory tests, including liver enzymes, gluco-insulinemic profile and lipids will be performed at baseline and repeated at 6-12 months

Official Title
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Efficacy and Tolerability of Vitamin D and Docosahexaenoic Acid (DHA) in Children With Biopsy Proven NAFLD

Conditions
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NAFLD, Non Alcoholic Steatohepatitis (NASH)

Intervention / Treatment
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* Drug: DHA plus Vitamin D
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: biopsy consistent with the diagnosis of NAFLD/NASH reduced serum levels of vitamin D aminotransferases (ALT) levels <10 upper limit of normal hyperechogenicity at liver ultrasound examination suggestive of fatty liver International normalized ratio (INR) < 1,3 Albumin > 3 g/dl total bilirubin < 2,5 mg/dl no previous gastrointestinal bleeding no previous portosystemic encephalopathy normal renal function no hepatitis B, hepatitis C infection normal cell blood count Exclusion Criteria: alcohol consumption 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 every clinical or psychiatric disease interfering with experimentation according to investigator's evaluation finding of active liver disease due to other causes

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TREATED GROUP<br>this group will treated with pearls containing DHA plus Vitamin D3 (500 mg and 800 IU, respectively) given orally in association with lifestyle intervention [hypocaloric diet (25-30 Kcal/kg/day) or isocaloric (40-45 Kcal/kg/day) and physical activity] for 24 weeks | Drug: DHA plus Vitamin D<br>* DHA 500 mg plus Vitamin D 800 IU<br>|
| Placebo Comparator: PLACEBO GROUP<br>this group will treated with identical placebo pearls given orally in association with lifestyle intervention [hypocaloric diet (25-30 Kcal/kg/day) or isocaloric (40-45 Kcal/kg/day) and physical activity] for 24 weeks | Drug: Placebo<br>* Placebo pearls mimicking pearls with DHA and Vitamin D<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in NAFLD Activity Score (NAS) |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improvement of laboratory parameters of metabolic syndrome, such as lipids and gluco-insulinemic profile |  | at 6 and 12 months | 
| safety | clinical examination, medical history and specific laboratory parameters | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NAFLD, NASH, DHA, VITAMIN D, OBESITY, CHILDREN