Safety and Efficacy of Omega-3 Free Fatty Acids in Adolescents With Obesity and Hypertriglyceridemia.
Condition: Hypertriglyceridemia; Pediatric Obesity
MeSH terms: Obesity; Hypertriglyceridemia; Pediatric Obesity
Study type: Interventional

Summary: 
      The primary objetive was to evaluate the safety and efficacy the 3 grams per day of omega-3
      in adolescents with obesity and hypertriglyceridemia ( ≥ 150 mg/dl and ≤ 1000 mg/dl) for 12
      weeks, compared with placebo. Half of subjects received 3 grams of omega 3, while the other
      half received placebo.
    

Detailed description: 
      First of all, the omega-3 free fatty acids have an important effect for lowering
      triglycerides through three potential mechanisms such as:

      Inhibition of triacylglycerol synthesis as direct inhibition of diacyl glycerol acetyl
      transferase and phosphatidic acid phosphohydrolase results in lowering triacylgycerol
      production.

      Simulation of fatty acid oxidation through activation of peroxisome proliferation activated
      receptor stimulates hepatic mitochondrial and peroxisomal beta oxidation of fatty acids.
      Decreased availability of fatty acids for triacylgylcerol synthesis results in lowering
      plasma triacylgycerol levels Lipoprotein Lipase mediated clearance. One of the first
      randomized double blind placebo controlled clinical trials was managed by Harris in 1997 in
      adult subjects with an average age of 46 ± 11 years and severe hypertriglyceridemia (500-2000
      mg / dl) 20 subjects received placebo and 22 subjects 4 grams of omega-3. The mean percent
      change from baseline in the omega-3 group was -45 ± 23% and in the placebo group was -16 ±
      35% (p <0.0001).

      Also, more clinical trials have recently been conducted with similar results such as the most
      recent randomized, double-blind, placebo-controlled clinical trial that was conducted by
      Ta-Chen Su in Taiwan in adults with hypetriglyceridemia (200-1000 mg / dl). The first group
      received 4 grams of omega-3 (n = 84), the second group received 2 grams of omega-3 (n = 82)
      and the third group received placebo (n = 87). The mean percent change from baseline in the 4
      grams of omega-3 group was -32.1%, in the 2 grams group of omega-3 was -29.7% and in the
      placebo group was -5.4% (p <0.0001) What is more, the strongest scientific evidence in favor
      of supplementation of omega-3 acids fatty was determined by two meta-analysis, the first
      study was published by Harris in 1997 that included 72 placebo-controlled clinical trials,
      the study showed a reduction of 25-30% triglycerides levels with doses of 3-4 g omega-3
      compared with placebo in subjects with triglycerides levels ≥500mg / dl. The second
      meta-analysis by Balk that included 17 clinical trials (7,803 patients) with different doses
      of omega-3 (0.8-5.4 g). The net reduction in triglycerides levels was -27 mg / dl (IC95%
      22-30), p <0.0001 In addition, the American Heart Association based on the meta-analysis by
      Harris currently recommends the administration of 2 to 4 grams of omega-3 per day for the
      treatment of severe hypertriglyceridemia (≥500mg / dl) in adult patients.

      Secondly, the Task Force for the Management of Dyslipidaemias of the European Society of
      Cardiology (ESC) and European Atherosclerosis Society (EAS) currently recommends that if
      hypertriglyceridemia is not able to reduce with statins or fibrates the physician will
      prescribe 2-4 grams of omega-3 fatty acids to reduce triglyceride levels in adult patients.

      Finally, the Food Drug Administration (FDA) in 2004 authorized the administration of 2 to 4
      grams of omega-3 per day for the treatment of severe hypertriglyceridemia (≥500mg / dl) in
      adult patients.

      There is enough evidence that medical literature supports the use of omega-3 in adult
      patients for treatment of hypertrigyceridemia even the American Heart Association has made
      the recommendation in its Scientific Statement but unfortunately in children the information
      about the use of omega-3 for hypertriglyceridemia is insufficient to make clinical decisions.

      There are no specific recommendations and dosages of omega-3 in children and adolescents for
      the treatment of hypertriglyceridemia.

      A randomized, double-blind placebo controlled clinical trials are necessary to assess the
      efficacy and safety of omega-3 fatty acids for the treatment of hypertriglyceridemia in
      children and adolescents.

      Main objective:

      Assessing the efficacy and safety of supplementation of 3 grams of omega-3 fatty acids for 12
      weeks on serum triglycerides in adolescents with obesity and hypertriglyceridemia compared to
      a control group that received placebo.

      Secondary objective:

      Assessing the efficacy and safety of supplementation of 3 grams of omega-3 fatty acids for 12
      weeks on serum cholesterol, HDL-C, glucose and uric acid in adolescents with obesity and
      hypertriglyceridemia compared to a control group that received placebo.

      Study plan detailing the procedures.

      Visit 1 Enrollment:

      The subject was picked up by the Allergy Department and Obesity Clinic. Informed consent and
      informed assent. Demography (date of birth, gender) and evaluation of Inclusion/Exclusion
      criteria Medical. Surgical history physical examination and anthropometry (weight, height,
      body mass index, abdominal perimeter, waist and hip). Pulse and blood pressure. Pregnancy
      test. Fasting venous blood samples of 12 hours for the measurement of triglycerides and
      metabolic profile. Food recommendation was indicated by the Pediatric Clinical Nutrition
      Service. Physical activity was indicated with a 30-minute walk per day for seven days per
      week by the Pediatric Clinical Nutrition service.

      Visit 2 Randomization:

      Triglyceride levels were reviewed, in case of report ≥150 mg / dl and ≤ 1000 mg/dl the
      subjects were randomized.

      The type of randomization used was blocked randomisation, number of subjects per block were
      10 and number of blocks were 13. (130 subjects were randomized).

      Allocation of omega-3 or placebo capsules for all randomized subjects and beginning of the
      week 0 of treatment.

      Visit 3 Treatment week 4 Allocation of omega-3 or placebo capsules. Checking of adverse
      effects. Accounting of capsules. Supervision of compliance diary of omega-3 or placebo
      capsules. Supervision of compliance diary food recommendation. Supervision of compliance
      physical activity

      Visit 4 Treatment week 8 Allocation of omega-3 or placebo capsules. Checking of adverse
      effects. Accounting of capsules. Supervision of compliance diary of omega-3 or placebo
      capsules. Supervision of compliance diary food recommendation. Supervision of compliance
      physical activity.

      Visit 5 Treatment week 12 Checking of adverse effects. Accounting of capsules. Supervision of
      compliance diary of omega-3 or placebo capsules. Supervision of compliance diary food
      recommendation. Supervision of compliance physical activity.

      Follow-up telephone call week 16. A follow-up telephone was performed 4 weeks after the visit
      5. At the follow-up telephone call, the investigator checked adverse events.
    

Intervention name(s): Omega-3 fatty acid 3 grams per day; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Each capsule contains 400 mg of eicosapentaenoic acid and 200 mg of docosahexaenoic acid. We allocated five capsules per day, three in the morning and two at night, every 12 hours (8.00 am and 8:00 pm), therefore the subject ingest 2000 mg of eicosapentaenoic acid and 1000 mg of docosahexaenoic acid per day (3 gr of Omega 3 per day) by mouth for 12 weeks. The trademark is Omega RX Dr.Sears Zone labs Inc.; Placebo Comparator: Placebo Each capsule contains 600 mg of soybean oil. We allocated five capusles per day, three in the morning and two at night, every 12 hours (8.00 am and 8:00 pm), therefore the subject ingest 3000 mg of soybean oil per day (3 gr soya oil per day) by mouth for 12 weeks.
Other intervention name(s): Omega-3; Soybean oil
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, double-blind, placebo-controlled clinical trial
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: hypertriglyceridemia; pediatric obesity; omega 3