Safety and Efficacy of Omega-3 Free Fatty Acids in Adolescents With Obesity and Hypertriglyceridemia.

Pediatric Obesity Clinical Trial

Official title:

A Randomized, Double Blind, Placebo-controlled Clinical Trial to Assess the Safety and Efficacy of Omega-3 Free Fatty Acids in Adolescents With Obesity and Hypertriglyceridemia.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03216057
• Other study ID #: HIM/2008/006
• Status: Completed
• Phase: N/A
• First received: July 10, 2017
• Last updated: July 10, 2017
• Start date: May 20, 2008
• Est. completion date: November 22, 2016

Study information

• Verified date: July 2017
• Source: Hospital Infantil de Mexico Federico Gomez
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 168
• Est. completion date: November 22, 2016
• Est. primary completion date: November 22, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 16 Years

Eligibility

Inclusion Criteria:

• Ages 10-16 years old

• Informed consent from a parent or legal guardian of minors or adult subject

• Written assent from the adolescent to participate in the study

• Obese patients (Body Mass Index =95th percentile according to the National Center for Health Statistics, Center for Disease Control and Prevention [CDC].

• Fasting Serum triglycerides =150 mg/dL and =1000 mg/dL.

• Cooperation to ingest capsules (omega-3 or placebo) and taking laboratories

Exclusion Criteria:

• The subjects must not had received pharmacology treatment for hypertriglyceridemia six months before and at the time of enrollment.

• Treatment with medications that affect triglyceride levels, including oral hypoglycemic agents or insulin.

• Pregnancy or positive urine pregnancy test for those females who have begun menstruating.

• Known Bleeding Disorder or Coagulopathy or treatment with anticoagulant medications or low platelet counts, abnormal PT, or PTT.

• Subjects with mental delayed.

• Neurological disorder.

• Subjects with Cardiophaty

• Subjects with gastroesophageal reflux

• Endocrinopathies such as thyroid disorder, Hypothalamic disorder and Type 1 or 2 diabetes or fasting glucose that is >=126 mg/dl.

• Subjects with liver disease

• Familial hypertriglyceridemia.

• Familial hypercholesterolemia

• Polycystic ovary syndrome

• Use of contraceptives by any way of administration 6 months before and at the time of enrollment.

• Use of vitamins 6 months before and at the time of enrollment.

• Allergy to fish oil.

• Allergy to soybean oil.

Elimination criteria:

• Subject or parents´ subject either decision to discontinue of the study at any time without prejudice to further treatment.

• Serious adverse event.

• Safety reason as judged by the investigator.

• Pregnancy.

Related Conditions & MeSH terms

• Hypertriglyceridemia
• Obesity
• Pediatric Obesity

Intervention

Dietary Supplement:
• Omega-3 fatty acid 3 grams per day
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
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.

Locations

Country	Name	City	State
n/a

Sponsors (5)

Lead Sponsor	Collaborator
Hospital Infantil de Mexico Federico Gomez	Fengyang Huang, Hall Mondragon Margareth Sharon, Leija Martinez José de Jesús, Miranda Lora América Liliana

References & Publications (10)

Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J. Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review. Atherosclerosis. 2006 Nov;189(1):19-30. Epub 2006 Mar 10. Review. — View Citation

Bays HE, Tighe AP, Sadovsky R, Davidson MH. Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications. Expert Rev Cardiovasc Ther. 2008 Mar;6(3):391-409. doi: 10.1586/14779072.6.3.391. Review. — View Citation

Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, Hoes AW, Jennings CS, Landmesser U, Pedersen TR, Reiner Ž, Riccardi G, Taskinen MR, Tokgozoglu L, Verschuren WM, Vlachopoulos C, Wood DA, Zamorano JL. [2016 ESC/EAS Guidelines for the Ma — View Citation

Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, Berglund L, Osmundsen K. Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovasc Risk. 1997 Oct-Dec;4(5-6):385-91. — View Citation

Harris WS. n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997 May;65(5 Suppl):1645S-1654S. Review. — View Citation

Jacobson TA. Role of n-3 fatty acids in the treatment of hypertriglyceridemia and cardiovascular disease. Am J Clin Nutr. 2008 Jun;87(6):1981S-90S. — View Citation

Kastelein JJ, Maki KC, Susekov A, Ezhov M, Nordestgaard BG, Machielse BN, Kling D, Davidson MH. Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: the EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial. J Clin Lipidol. 201 — View Citation

Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, Goldberg AC, Howard WJ, Jacobson MS, Kris-Etherton PM, Lennie TA, Levi M, Mazzone T, Pennathur S; American Heart Association Clinical Lipidology, Thrombosis, and Prevention Committee of — View Citation

Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW; American College of Cardiology/American Heart Association Task Fo — View Citation

Su TC, Hwang JJ, Huang KC, Chiang FT, Chien KL, Wang KY, Charng MJ, Tsai WC, Lin LY, Vige R, Olivar JE, Tseng CD. A Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Assess the Efficacy and Safety of Ethyl-Ester Omega-3 Fatty Acid in Taiwanes — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change from baseline in Triglyceride	Percent change in triglyceride from baseline to week 12 of study treatment	12 weeks
Primary	Fasting Triglycerides	Fasting Triglycerides from baseline to week 12 of study treatment	12 weeks
Secondary	Percent Change from baseline in cholesterol	Percent Change in cholesterol from baseline to week 12 of study treatment	12 weeks
Secondary	Fasting Cholesterol	Fasting Cholesterol from baseline to week 12 of study treatment	12 weeks
Secondary	Percent Change from baseline in HDL-C	Percent Change in HDL-C from baseline to week 12 of study treatment	12 weeks
Secondary	Fasting HDL-C	Fasting HDL-C from baseline to week 12 of study treatment	12 weeks
Secondary	Percent Change from baseline in glucose	Percent Change in glucose from baseline to week 12 of study treatment	12 weeks
Secondary	Fasting glucose	Fasting glucose from baseline to week 12 of study treatment	12 weeks
Secondary	Percent Change from baseline in Uric Acid	Percent Change in Uric Acid from baseline to week 12 of study treatment	12 weeks
Secondary	Fasting Uric Acid	Fasting Uric Acid from baseline to week 12 of study treatment	12 weeks