DHA and Vitamin D in Children With Biopsy-proven NAFLD (VitD_DHA)

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

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).

Study Overview

• Status: Completed
• Conditions: NAFLD; Non Alcoholic Steatohepatitis (NASH)
• Intervention / Treatment: Drug: DHA plus Vitamin D; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00165
    • Bambino Gesu Children Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TREATED GROUP; 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; DHA 500 mg plus Vitamin D 800 IU
Placebo Comparator: PLACEBO GROUP; 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; Placebo pearls mimicking pearls with DHA and Vitamin D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Bambino Gesù Hospital and Research Institute
• Investigators: Principal Investigator: Valerio Nobili, Professor, Bambino Gesu Children Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: March 24, 2014
• First Submitted That Met QC Criteria: March 26, 2014
• First Posted (Estimate): March 28, 2014

Study Record Updates

• Last Update Posted (Estimate): January 14, 2016
• Last Update Submitted That Met QC Criteria: January 13, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: NAFLD; NASH; DHA; CHILDREN; VITAMIN D; OBESITY
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: VD3_DHA_NAFLD