Clinical trial NCT01908374: Bioavailability of EPA and DHA From Two Dietary Supplements
Official title: A Randomized, Controlled, Crossover Study to Evaluate the Acute and Subchronic Bioavailability of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) From Two Dietary Supplements in Men and Women With Mildly Elevated Triglycerides
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hypertriglyceridemia
Keywords: Active-placebo controlled double blind cross over
Lead sponsor: Arctic Nutrition AS
Sponsor class: INDUSTRY
Collaborators: name: BioFortis
name: University of British Columbia
First posted: 2013-07-25
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to test the effects of two different fish oil products containing DHA and EPA by comparing the omega-3 fatty acid levels in the blood.

Detailed description: The objective of this study is to evaluate and compare the acute and sub-chronic (2 week) bioavailability of EPA and DHA from two marine oil supplements consumed with a meal in men and women with mildly elevated triglycerides. The supplements provide similar amounts of EPA + DHA esterified as either triglycerides; or esterified as phospholipids and triglycerides.

Eligibility criteria: Inclusion Criteria:

1. Subject is male or female, 18-59 years of age, inclusive.
2. Subject has a body mass index (BMI) of ≥18.50 and ≤29.99 kg/m2 at visit 1b (day -7).
3. Subject has a score of 7 to 10 on the Vein Access Scale at visit 1b (day -7; Appendix 3).
4. Subject has no health conditions that would prevent him/her from fulfilling the study requirements as judged by the Investigator on the basis of medical history and routine laboratory test results.
5. Subject has a fasting TG 100-249 mg/dL at visit 1b (day -7). One venous retest allowed if ≥250 mg/dL.
6. Subject is willing to refrain from consumption of all fish/seafood (including shellfish), foods rich in choline, fatty acid-containing foods and supplements, and/or EPA-, DHA-containing foods and supplements (≤1.0 g/d ) 14 d prior to visit 2 (day 0) and throughout the study (Appendix 1).
7. Subject is willing to limit alcohol consumption to no more than 1 drink/d following visit 1b (day -7) and throughout the study.
8. Subject has no plans to change smoking habits during the study period and agrees to abstain from tobacco products for at least 1 h prior to and throughout the duration of the clinic visits \[visits 1b, 3 and 5 (days -7, 14 and 56) for up to 2 h; and visits 2 and 4 (days 0 and 42) for up to 14 h\].
9. Subject is willing to comply with fecal collection procedures.
10. Subject is willing to maintain habitual diet (with the exception of foods to be restricted), physical activity patterns, and body weight throughout the trial.
11. Subject understands the study procedures and signs forms providing informed consent to participate in the study and authorization for release of relevant protected health information to the study Investigator.

Exclusion Criteria:

1. Subject is male or female, 18-59 years of age, inclusive.
2. Subject has a body mass index (BMI) of ≥18.50 and ≤29.99 kg/m2 at visit 1b (day -7).
3. Subject has a score of 7 to 10 on the Vein Access Scale at visit 1b (day -7; Appendix 3).
4. Subject has no health conditions that would prevent him/her from fulfilling the study requirements as judged by the Investigator on the basis of medical history and routine laboratory test results.
5. Subject has a fasting TG 100-249 mg/dL at visit 1b (day -7). One venous retest allowed if ≥250 mg/dL.
6. Subject is willing to refrain from consumption of all fish/seafood (including shellfish), foods rich in choline, fatty acid-containing foods and supplements, and/or EPA-, DHA-containing foods and supplements (≤1.0 g/d ) 14 d prior to visit 2 (day 0) and throughout the study (Appendix 1).
7. Subject is willing to limit alcohol consumption to no more than 1 drink/d following visit 1b (day -7) and throughout the study.
8. Subject has no plans to change smoking habits during the study period and agrees to abstain from tobacco products for at least 1 h prior to and throughout the duration of the clinic visits \[visits 1b, 3 and 5 (days -7, 14 and 56) for up to 2 h; and visits 2 and 4 (days 0 and 42) for up to 14 h\].
9. Subject is willing to comply with fecal collection procedures.
10. Subject is willing to maintain habitual diet (with the exception of foods to be restricted), physical activity patterns, and body weight throughout the trial.
11. Subject understands the study procedures and signs forms providing informed consent to participate in the study and authorization for release of relevant protected health information to the study Investigator.

Primary outcomes:
measure: Area under the curve for plasma phosphatidylcholine omega-3 fatty acids
timeFrame: pre-dose, 1, 2, 4, 6, 8, 10, 12 hours post-dose
Secondary outcomes:
measure: Maximum concentration and Time to maximum concentration for plasma omega-3 phosphatidylcholine fatty acids
timeFrame: pre-dose, 1, 2, 4, 6, 8, 10, 12 hours post-dose
measure: Area under the curve for plasma phosphatidylcholine omega-3 fatty acids Part 2
timeFrame: pre-dose, 1, 2, 4, 6, 8, 10, 12 hours post-dose
measure: Plasma sphingomyelin and total plasma phosphatidylcholine
timeFrame: pre-dose, 0, 1, 2, 4, 6, 8, 10, 12 hours post-dose
measure: Fasting plasma lipoprotein lipids
timeFrame: pre-dose
measure: Gastrointestinal (GI) Tolerability Questionnaire
timeFrame: 0, 12 hours post-dose
measure: Product Acceptability Questionnaire
timeFrame: 0, 12 hours post-dose
measure: Adverse Events (AE)
timeFrame: pre-treatment, 0, 12 hours post-dose
Other outcomes:
Locations:
city: Addison
country: United States
facility: Biofortis
state: Illinois
Study officials:
affiliation: BioFortis
name: Kevin C Maki, Ph. D
role: STUDY_DIRECTOR
affiliation: BioFortis
name: Kathleen Kelley, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Davidson MH, Maki KC, Bays H, Carter R, Ballantyne CM. Effects of prescription omega-3-acid ethyl esters on lipoprotein particle concentrations, apolipoproteins AI and CIII, and lipoprotein-associated phospholipase A(2) mass in statin-treated subjects with hypertriglyceridemia. J Clin Lipidol. 2009 Oct;3(5):332-40. doi: 10.1016/j.jacl.2009.08.001. Epub 2009 Aug 31.
citation: Davidson MH, Johnson J, Rooney MW, Kyle ML, Kling DF. A novel omega-3 free fatty acid formulation has dramatically improved bioavailability during a low-fat diet compared with omega-3-acid ethyl esters: the ECLIPSE (Epanova((R)) compared to Lovaza((R)) in a pharmacokinetic single-dose evaluation) study. J Clin Lipidol. 2012 Nov-Dec;6(6):573-84. doi: 10.1016/j.jacl.2012.01.002. Epub 2012 Jan 24.
citation: Grimsgaard S, Bonaa KH, Hansen JB, Nordoy A. Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids. Am J Clin Nutr. 1997 Sep;66(3):649-59. doi: 10.1093/ajcn/66.3.649.
citation: Maki KC, Reeves MS, Farmer M, Griinari M, Berge K, Vik H, Hubacher R, Rains TM. Krill oil supplementation increases plasma concentrations of eicosapentaenoic and docosahexaenoic acids in overweight and obese men and women. Nutr Res. 2009 Sep;29(9):609-15. doi: 10.1016/j.nutres.2009.09.004.
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 the Council on Nutrition, Physical Activity, and Metabolism; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Nursing; Council on the Kidney in Cardiovascular Disease. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011 May 24;123(20):2292-333. doi: 10.1161/CIR.0b013e3182160726. Epub 2011 Apr 18. No abstract available.
citation: Mori TA, Burke V, Puddey IB, Watts GF, O'Neal DN, Best JD, Beilin LJ. Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am J Clin Nutr. 2000 May;71(5):1085-94. doi: 10.1093/ajcn/71.5.1085.
citation: Schuchardt JP, Schneider I, Meyer H, Neubronner J, von Schacky C, Hahn A. Incorporation of EPA and DHA into plasma phospholipids in response to different omega-3 fatty acid formulations--a comparative bioavailability study of fish oil vs. krill oil. Lipids Health Dis. 2011 Aug 22;10:145. doi: 10.1186/1476-511X-10-145.
citation: Ulven SM, Kirkhus B, Lamglait A, Basu S, Elind E, Haider T, Berge K, Vik H, Pedersen JI. Metabolic effects of krill oil are essentially similar to those of fish oil but at lower dose of EPA and DHA, in healthy volunteers. Lipids. 2011 Jan;46(1):37-46. doi: 10.1007/s11745-010-3490-4. Epub 2010 Nov 2.