Omega-3 Fatty Acid Supplementation in Children

Study Overview
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Brief Summary
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Children with Chronic Kidney Disease (CKD) are at very high risk for cardiovascular morbidity and mortality. Hyper-lipidemia, a traditional risk factor for Cardiovascular Disease (CVD), occurs early in the progression of kidney failure; timely identification and intervention is prudent. Currently, there is no known effective therapy for hypertriglyceridemia, the most common lipid abnormality. n-3FA, in doses ranging from 2-6 g/day have effectively lowered elevated triglyceride (TG) levels by 20-50% in a variety of adult populations; however, their use in children with CKD has not been tested in a randomized controlled fashion. This study will provide important information on the safety, efficacy and tolerance of n-3FA in lowering elevated TG levels in children and adolescents with CKD.

Detailed Description
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Following counseling on dietary and lifestyle changes to lower triglyceride levels, and a period of applying these modifications, children will be assigned in a random fashion to take either fish oil supplements or a placebo (soybean/corn oil) for 8 weeks. After this 8-week treatment period, children will not take a supplement for 4 weeks and then will be assigned the alternate product (fish oil or placebo) for another 8 weeks. Our main interest is to see whether there is a larger decrease in triglyceride levels after taking the fish oil supplement compared to the placebo. The primary objective of this study is to determine whether omega-3 fatty acid supplements, given at therapeutic dosages over an 8-week period, significantly decrease elevated serum TG in children with CKD; The secondary objectives of this study are: i. To evaluate the effect of n-3 fatty acid supplements on total-, LDL-, and HDL-cholesterol; ii. To determine whether n-3 fatty acid supplements are well tolerated by our study participants; and iii. To test whether TG-lowering effects are sustained up to 4 weeks after stopping supplements.

Official Title
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Omega-3 Fatty Acid Supplementation to Treat Hypertriglyceridemia in Children With Chronic Kidney Disease

Conditions
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Chronic Kidney Disease, Hypertriglyceridemia

Intervention / Treatment
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* Dietary Supplement: n-3 Fatty Acid supplement
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age at randomization: 2.0-17.4 years old (stratified by age: 2-8 yr, 9-13 yr, 14-17.4 yr) CKD stages 3 or 4 (GFR:15-59 ml/min/1.73 m2) established and stable in the CKD 3 and 4 Program for a minimum of 3 months fasting serum TG 95th percentile for age and gender 2 on more than or equal to 2 occasions Exclusion Criteria: allergy to fish, corn, soybean anti-coagulant or anti-platelet drugs (heparin, warfarin, therapeutic NSAIDs) or herbal products (ginko, garlic, feverfew, ginger and ginseng) known to prolong bleeding currently undergoing treatment for dyslipidemia use of dietary supplements containing n-3FA children with Nephrotic Syndrome, on dialysis, or transplanted planned surgery, dialysis or transplantation within the next 7 months children with diabetes bleeding and clotting disorders: thrombocytopenia (platelet count <100 x 109/L), including ITP, TTP Von Willebrands disease hemophilia thrombophilia vitamin K deficiency severe liver disease unstable patients with shock which can lead to DIC (disseminated intravascular coagulation) active Henoch Schonlein Purpura hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease)

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Supplement<br> | Dietary Supplement: n-3 Fatty Acid supplement<br>* Children will be prescribed 1600-1800 mg EPA + DHA per m2 Body Surface Area, to a maximum of the upper limit of the age-appropriate range recommended by Health Canada. Each n-3FA gel capsule (1000 mg) will contain 400 mg EPA and 200 mg DHA derived from the oil of wild anchovies and sardines. A smaller gel capsule (500 mg; 200 mg EPA + 100 mg DHA) will be available for children unable to swallow large solid medication and a flavored liquid formulation, containing a similar proportion of EPA + DHA (2200 mg fish oil concentrate from anchovies and sardines, 750 mg EPA, 375 mg DHA per ½ teaspoon), will be available for use in toddlers and older children unable to swallow gel capsules.<br>|
| Placebo Comparator: Control<br> | Dietary Supplement: Placebo<br>* The placebo, identical in opaque appearance and citrus-flavored taste, will contain a 50:50 blend of soybean and corn oil for both gel capsule (2 sizes) and liquid formulations.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Blood Lipid Profiles(TG levels) |  | Week 1,4,12,16,24 and 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet aggregation |  | Week 1,4,12,16,24 and 28 | 
| CBC |  | Week 1,4,12,16,24 and 28 | 
| Cholesterol Levels (LDL and HDL) |  | Week 1,4,12,16,24 and 28 | 
| Tolerability of n-3 fatty acid supplements by our participants | Sustainability of TG-lowering effects up to 4 weeks after stopping supplements | Week 1,4,12,16,24 and 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CKD, hypertriglyceridemia, Fatty Acid Supplementation, Children, Omega-3