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Potential Role of n-3 Fatty Acids in the Treatment of NAFLD in Pediatric Patients

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ClinicalTrials.gov Identifier: NCT02201160
Recruitment Status : Unknown
Verified July 2014 by Emile Levy, St. Justine's Hospital.
Recruitment status was:  Active, not recruiting
First Posted : July 25, 2014
Last Update Posted : July 25, 2014
Sponsor:
Collaborator:
Nutrisanté Canada
Information provided by (Responsible Party):
Emile Levy, St. Justine's Hospital

Brief Summary:
Nonalcoholic hepatic steatosis (NASH) is defined as the amount greater than 5% of the total liver volume fat. Commonly known as NASH, it includes 4 stages histological ranging from the mere presence of fat to the existence of fibrosis and degeneration of hepatocytes, and finally a progression to cirrhosis, sometimes accompanied by complications of hepatocellular carcinoma. It is a common condition associated with a combination of disorders, namely obesity, insulin resistance and type 2 diabetes. The link with the metabolic syndrome (MetS) was mainly studied in the adult population and very little in the paediatric population, while 15 and 25% of obese children are affectés. The severity of histological disease appears to be associated with the degree of obesity in children and particularly in the MetS. in addition, epidemiological data indicate that the incidence of this disease is increasing in children and positioning as the first NASH liver disease in North America. the revelation of the factors associated with the occurrence of NASH is a first necessary step to understanding this disorder worrying for the future of children and adolescents. In addition, clarification of the mechanisms responsible for its development is essential if the investigators want to consider targeted and effective treatments to slow the rat race of NASH, which stands out as the supreme chronic liver accompanying the obesity and MetS. Finally, in view of growth and puberty of children, it would be extremely beneficial to find nutritional avenues that would avoid the side effects of chemical agents.

Condition or disease Intervention/treatment Phase
Non Alcoholic Fatty Liver Disease (NAFLD) Dietary Supplement: omega 3 Phase 1 Phase 2

Detailed Description:

The aims of the investigators studies are to determine the plasma FA composition and to assess changes in the latter in response to n-3 supplementation in French-Canadian youth since (i) none of the available pharmacological agents could be recommended for treatment of children with NAFLD; (ii) n-3 PUFA are quite safe diet supplements that showed efficacy in the prevention and therapy of cardiovascular diseases, dyslipidemia and metabolic syndrome; (iii) loss of n-3 PUFA dietary intake was found in pediatric NAFLD and (iii) no attention has been given to French-Canadian population, which is primarily and historically located in the province of Quebec, has the highest prevalence worldwide of lipoprotein lipase deficiency, includes a large pool of individuals at risk for atherosclerosis and other lipid-related diseases, and exhibits a founder effect among the 8,000 ancestors of present-day French-Canadians, who have had relatively little cross-breeding with individuals from other national origin groups.

Subjects The present randomized clinical trial was performed on 30 NAFLD children followed as outpatients at the Gastroenterology/Hepatology and Nutrition clinic of MCHU Ste-Justine and the Gastroenterology division of the Montreal Children's Hospital, Montreal.

The children have between 8 years and 18 years of age, with obesity and a diagnostic of NAFLD based on the results of a clinical evaluation, liver echography, and magnetic resonance imaging-proton density fat fraction.

Inclusion and exclusion criteria The children are eligible for the study if they are boys (according to the literature review on NAFLD prevalence), with a body weight ≥ 95th percentile (based on the CDC Chart), aged <18 years, have a diffusely hyperechogenic liver at ultrasonography (consistent with NAFLD diagnostic), and have normal or high transaminases (> 2N). Moreover, the exclusion criteria is based on subjects having pin or cochlear implants may affect the magnetic resonance imaging examination; subjects who consumed natural medicine products have an increased risk of haemorrhage, and those in whom a surgical procedure was planned, and the child who founded to consume fish, flaxseed oil and foods enriched with n-3 PUFA (eggs, or milk containing n-3 PUFA supplements), probiotics, vitamin E or use of drugs known to induce fatty liver during the study.

Study design The present study is a 6-month, double-blind, one-way, crossover randomized study. The treatment consisting of n-3 PUFA supplement (NutriSanté Inc./Ponroy, Canada), administered in two phases, each of 3-month duration. In the first phase, an NAFLD group will receive an active n-3 PUFA supplement and another will receive equivalent quantities of sunflower oil as a placebo. During the second phase (after the first 3 months), all NAFLD subjects will receive an active n-3 PUFA. The study is approved by the Clinical Research Ethics Committee of MUCH Ste-Justine (Montreal, Quebec. Informed consent was obtained from all subjects before starting experimental procedures, and the study followed the Helsinki guidelines.

Dosing The dose supplementation considered for this study is 2.0 g of fish oil per day, providing a total of 1.2 g of n-3 PUFA. This dose is chosen according to official recommendations, based on our previous studies and pediatric clinical trials. Compliance to the study treatment will be evaluated by pill count at every visit, review of medication records, and direct interview of patients by the physician.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Impact of n-3 Fatty Acid Supplementation on the Metabolic Abnormalities in Children With NAFLD
Study Start Date : January 2009
Actual Primary Completion Date : December 2013
Estimated Study Completion Date : December 2015


Arm Intervention/treatment
Active Comparator: omega 3
The subjects will take 4 capsules/day during 6 months. Each capsule of the active n-3 PUFA supplement contained 500 mg of fish oil (each capsule provides 300 mg of n-3 PUFA (EPA+DHA) with 3.75 U vitamin E to prevent peroxidation).
Dietary Supplement: omega 3
Two groups from our cohort will be supplemented either with omega-3 PUFA or placebo during 3 months. Each subject will take 4 capsules/d. after 3 months, the subjects under omega-3 will continue for another 3 months and the group under placebo will take omega-3 PUFA during another 3 months.

Placebo Comparator: Sun Flower
The subjects will take 4 capsules/day during 6 months. The placebo capsule contained 500 mg of sunflower oil with 3.75 U vitamin E.
Dietary Supplement: omega 3
Two groups from our cohort will be supplemented either with omega-3 PUFA or placebo during 3 months. Each subject will take 4 capsules/d. after 3 months, the subjects under omega-3 will continue for another 3 months and the group under placebo will take omega-3 PUFA during another 3 months.




Primary Outcome Measures :
  1. Efficacy of omega 3 PUFA supplementation in NAFLD subjects compared to placebos [ Time Frame: 24 weeks ]

    Two groups from our cohort will be double blind supplemented either with n-3 PUFA or sun flower (as a placebo).

    The specific primary outcome is to assess the activities of hepatic plasma transaminase enzymes (ALT/AST/GGT) in the omega 3 group and to determine their decrease to the normal range.



Secondary Outcome Measures :
  1. A composite mesures regarding the improvement of metabolic profile of NAFLD patients [ Time Frame: 24 weeks ]

    To determine

    • the decrease in obesity (body mass index)
    • insulin resistance (HOMA-IR)
    • Adipose tissue lowering (DEXA)
    • Oxidative stress (Malondialdehyde biomarker, oxLDL) Inflammation (TNFalpha, IL-6, leptin and resistine)
    • Plasma lipids (triglycerides, total cholesterol, LDL and HDL cholesterol)


Other Outcome Measures:
  1. Short term versus long-term treatment comparison [ Time Frame: 12 weeks vs. 24 weeks ]

    To compare the effectiveness of omega 3 PUFA between 12- and 24-weeks by a composite measures in terms of percent decrease in the

    • transaminases (ALT/AST/GGT)
    • body weight (BMI)
    • Insulin resistance (HOMA-IR)
    • Oxidative stress (malondialdehyde marker)
    • Inflammation (TNF-alpha, interleukin-6, leptin and resistin)
    • Lipids (triglycerides, cholesterol, LDL-cholesterol, HDL-cholesterol)
    • changes in adipose tissue (DEXA)



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Ages Eligible for Study:   8 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • boys (according to the literature review on NAFLD prevalence)
  • body weight ≥ 95th percentile (based on the CDC Chart)
  • aged <18 years
  • have a diffusely hyperechogenic liver at ultrasonography (consistent with NAFLD diagnostic)
  • have normal or high transaminases (> 2N).

Exclusion Criteria:

  • Subjects with pin or cochlear implants
  • Subjects who consumed natural medicine products
  • Those in whom a surgical procedure was planned
  • the child who were found to consume fish, flaxseed oil and foods enriched with n-3 PUFA (eggs, or milk containing n-3 PUFA supplements), probiotics, vitamin E or use of drugs known to induce fatty liver during the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02201160


Locations
Canada, Quebec
CHU Ste-Justine
Montreal, Quebec, Canada, H3T 1C5
Sponsors and Collaborators
St. Justine's Hospital
Nutrisanté Canada
Investigators
Principal Investigator: Emile Levy, Professor Research Centre, CHU STe-Justine

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Emile Levy, Full professor and researcher, St. Justine's Hospital
ClinicalTrials.gov Identifier: NCT02201160     History of Changes
Other Study ID Numbers: NAFLD-2188
First Posted: July 25, 2014    Key Record Dates
Last Update Posted: July 25, 2014
Last Verified: July 2014

Keywords provided by Emile Levy, St. Justine's Hospital:
NAFLD
Fatty acid composition
Omega 3 supplementation
Metabolism

Additional relevant MeSH terms:
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases