Clinical trial NCT02098317: DHA and Vitamin D in Children With Biopsy-proven NAFLD
Official title: Efficacy and Tolerability of Vitamin D and Docosahexaenoic Acid (DHA) in Children With Biopsy Proven NAFLD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: NAFLD
Non Alcoholic Steatohepatitis (NASH)
Keywords: NAFLD
NASH
DHA
VITAMIN D
OBESITY
CHILDREN
Lead sponsor: Bambino Gesù Hospital and Research Institute
Sponsor class: OTHER
First posted: 2014-03-28
Enrollment: 66
Sex: ALL
Minimum age (years): 4
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: Improvement in NAFLD Activity Score (NAS)
timeFrame: 12 months
Secondary outcomes:
measure: improvement of laboratory parameters of metabolic syndrome, such as lipids and gluco-insulinemic profile
timeFrame: at 6 and 12 months
measure: safety
timeFrame: 6 months
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Bambino Gesù Children Hospital
Study officials:
affiliation: Bambino Gesù Children Hospital
name: Valerio Nobili, Professor
role: PRINCIPAL_INVESTIGATOR
References: