Clinical trial NCT01061554: Bioavailability Study of Long Chain Omega-3 Fatty Acids From a Gastric Stable Emulsion
Official title: Correlation Between Level of Polyunsaturated Fatty Acid EPA and DHA in Blood After Digestion of ProBios Omega-3 Concordix™ Compared With Omega-3 Soft Capsules - a Pilot
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Bioavailability
Eicosapentaenoic acid
Docosahexaenoic acid
Soft gel capsules
Gastric stable emulsion
Omega-3
Tri-glycerides
Marine phospholipids
Lead sponsor: Ayanda AS
Sponsor class: INDUSTRY
First posted: 2010-02-03
Enrollment: 27
Sex: ALL
Minimum age (years): 19
Maximum age (years): 29
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to compare the short term absorption of EPA and DHA from triglycerides (TG) released from normal soft gel capsules and from the new patent pending vehicle providing a gastric stable emulsion.

Detailed description: The present study comprises the design of as well as the effect of pre-emulsification of ω-3 fatty acids on the bioavailability of docosahexaenoic acid and eicosapentaenoic acid. In-vitro studies have shown that long-term steric stabilization of an o/w-emulsion is obtained by arresting the oil droplets in a gelatin continuous gel matrix. The emulsion was also stable upon dissolution of the gel matrix at physiological conditions in-vitro and is hence referred to as a gastric stable emulsion (GSE).

In the bioavailability study, healthy young students were recruited and presented two different single-dose treatments of fish oil containing 5 grams of ω-3 fatty acids; one group receiving the fatty acids in traditional soft gel capsules, whereas the other group received the fatty acids using the GSE technology. Time resolved (2 - 26 hours) blood plasma analysis after intake of this single dose ω-3 fatty acids revealed significantly increased AUC0-26h and Cmax of EPA and EPA + DHA when administered as GSE compared to traditional soft gel capsules.

Eligibility criteria: Inclusion Criteria:

* Student at Nord-Trondelag University College
* Healthy (no known condition)
* Males and females aged 19 to 29 years

Exclusion Criteria:

* Fish allergies
* Ongoing consumption of omega-3 fatty acids
* Subjects receiving anticoagulation or non-steroid anti-inflammatory treatment
* Subjects with a known metabolic syndrome; diabetes, hypercholesterol, hypertension, obesity

Primary outcomes:
measure: The incremental (change from baseline) area under the blood plasma concentration curve of eicosapentaenoic acid (EPA)
timeFrame: 26 hours (blood samples taken at baseline and 2, 3, 4, 6, 8 and 26 hours after treatment administration)
measure: The incremental (change from baseline) area under the blood plasma concentration curve of docosahexaenoic acid (DHA)
timeFrame: 26 hours (blood samples taken at baseline and 2, 3, 4, 6, 8 and 26 hours after treatment administration)
measure: The incremental (change from baseline) area under the blood plasma concentration curve of Vitamin E
timeFrame: 26 hours (blood samples taken at baseline and 2, 3, 4, 6, 8 and 26 hours after treatment administration)
Secondary outcomes:
measure: The maximal incremental blood plasma concentration of EPA
timeFrame: 26 hours (blood samples taken at baseline and 2, 3, 4, 6, 8 and 26 hours after treatment administration)
measure: The maximal incremental blood plasma concentration of DHA
timeFrame: 26 hours (blood samples taken at baseline and 2, 3, 4, 6, 8 and 26 hours after treatment administration)
measure: The maximal incremental blood plasma concentration of Vitamin E
timeFrame: 26 hours (blood samples taken at baseline and 2, 3, 4, 6, 8 and 26 hours after treatment administration)
measure: The time passed since administration at which the incremental plasma concentration maximum occurs for EPA
timeFrame: 26 hours (blood samples taken at baseline and 2, 3, 4, 6, 8 and 26 hours after treatment administration)
measure: The time passed since administration at which the incremental plasma concentration maximum occurs for DHA
timeFrame: 26 hours (blood samples taken at baseline and 2, 3, 4, 6, 8 and 26 hours after treatment administration)
measure: The time passed since administration at which the incremental plasma concentration maximum occurs for Vitamin E
timeFrame: 26 hours (blood samples taken at baseline and 2, 3, 4, 6, 8 and 26 hours after treatment administration)
Other outcomes:
Locations:
city: Namsos
country: Norway
facility: Nord-Trøndelag University College
state: Nord-Trøndelag
Study officials:
References:
citation: Armand M, Borel P, Dubois C, Senft M, Peyrot J, Salducci J, Lafont H, Lairon D. Characterization of emulsions and lipolysis of dietary lipids in the human stomach. Am J Physiol. 1994 Mar;266(3 Pt 1):G372-81. doi: 10.1152/ajpgi.1994.266.3.G372.
citation: Armand M, Borel P, Pasquier B, Dubois C, Senft M, Andre M, Peyrot J, Salducci J, Lairon D. Physicochemical characteristics of emulsions during fat digestion in human stomach and duodenum. Am J Physiol. 1996 Jul;271(1 Pt 1):G172-83. doi: 10.1152/ajpgi.1996.271.1.G172.
citation: Armand M, Pasquier B, Andre M, Borel P, Senft M, Peyrot J, Salducci J, Portugal H, Jaussan V, Lairon D. Digestion and absorption of 2 fat emulsions with different droplet sizes in the human digestive tract. Am J Clin Nutr. 1999 Dec;70(6):1096-106. doi: 10.1093/ajcn/70.6.1096.
citation: Arterburn LM, Hall EB, Oken H. Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr. 2006 Jun;83(6 Suppl):1467S-1476S. doi: 10.1093/ajcn/83.6.1467S.
citation: Arterburn LM, Oken HA, Hoffman JP, Bailey-Hall E, Chung G, Rom D, Hamersley J, McCarthy D. Bioequivalence of Docosahexaenoic acid from different algal oils in capsules and in a DHA-fortified food. Lipids. 2007 Nov;42(11):1011-24. doi: 10.1007/s11745-007-3098-5. Epub 2007 Aug 23.
citation: Borel P, Pasquier B, Armand M, Tyssandier V, Grolier P, Alexandre-Gouabau MC, Andre M, Senft M, Peyrot J, Jaussan V, Lairon D, Azais-Braesco V. Processing of vitamin A and E in the human gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol. 2001 Jan;280(1):G95-G103. doi: 10.1152/ajpgi.2001.280.1.G95.
citation: Bucher HC, Hengstler P, Schindler C, Meier G. N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med. 2002 Mar;112(4):298-304. doi: 10.1016/s0002-9343(01)01114-7.
citation: Cao J, Schwichtenberg KA, Hanson NQ, Tsai MY. Incorporation and clearance of omega-3 fatty acids in erythrocyte membranes and plasma phospholipids. Clin Chem. 2006 Dec;52(12):2265-72. doi: 10.1373/clinchem.2006.072322. Epub 2006 Oct 19.
citation: Elvevoll EO, Barstad H, Breimo ES, Brox J, Eilertsen KE, Lund T, Olsen JO, Osterud B. Enhanced incorporation of n-3 fatty acids from fish compared with fish oils. Lipids. 2006 Dec;41(12):1109-14. doi: 10.1007/s11745-006-5060-3.
citation: Elvevoll EO, Eilertsen KE, Brox J, Dragnes BT, Falkenberg P, Olsen JO, Kirkhus B, Lamglait A, Osterud B. Seafood diets: hypolipidemic and antiatherogenic effects of taurine and n-3 fatty acids. Atherosclerosis. 2008 Oct;200(2):396-402. doi: 10.1016/j.atherosclerosis.2007.12.021. Epub 2008 Feb 1.
citation: Garaiova I, Guschina IA, Plummer SF, Tang J, Wang D, Plummer NT. A randomised cross-over trial in healthy adults indicating improved absorption of omega-3 fatty acids by pre-emulsification. Nutr J. 2007 Jan 25;6:4. doi: 10.1186/1475-2891-6-4.
citation: Grimsgaard S, Bonaa KH, Hansen JB, Myhre ES. Effects of highly purified eicosapentaenoic acid and docosahexaenoic acid on hemodynamics in humans. Am J Clin Nutr. 1998 Jul;68(1):52-9. doi: 10.1093/ajcn/68.1.52.
citation: Harris WS. Omega-3 fatty acids and cardiovascular disease: a case for omega-3 index as a new risk factor. Pharmacol Res. 2007 Mar;55(3):217-23. doi: 10.1016/j.phrs.2007.01.013. Epub 2007 Jan 25.
citation: Iso H, Kobayashi M, Ishihara J, Sasaki S, Okada K, Kita Y, Kokubo Y, Tsugane S; JPHC Study Group. Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: the Japan Public Health Center-Based (JPHC) Study Cohort I. Circulation. 2006 Jan 17;113(2):195-202. doi: 10.1161/CIRCULATIONAHA.105.581355. Epub 2006 Jan 9.
citation: Hsu, J. C. (1992). The Factor Analytic Approach to Simultaneous Inference in the General Linear Model. Journal of Computational and Graphical Statistics, 1(2), 151-168.
citation: Krokan HE, Bjerve KS, Mork E. The enteral bioavailability of eicosapentaenoic acid and docosahexaenoic acid is as good from ethyl esters as from glyceryl esters in spite of lower hydrolytic rates by pancreatic lipase in vitro. Biochim Biophys Acta. 1993 May 20;1168(1):59-67. doi: 10.1016/0005-2760(93)90266-c.
citation: Liu ZX, Artmann C. Relative bioavailability comparison of different coenzyme Q10 formulations with a novel delivery system. Altern Ther Health Med. 2009 Mar-Apr;15(2):42-6.
citation: London B, Albert C, Anderson ME, Giles WR, Van Wagoner DR, Balk E, Billman GE, Chung M, Lands W, Leaf A, McAnulty J, Martens JR, Costello RB, Lathrop DA. Omega-3 fatty acids and cardiac arrhythmias: prior studies and recommendations for future research: a report from the National Heart, Lung, and Blood Institute and Office Of Dietary Supplements Omega-3 Fatty Acids and their Role in Cardiac Arrhythmogenesis Workshop. Circulation. 2007 Sep 4;116(10):e320-35. doi: 10.1161/CIRCULATIONAHA.107.712984. No abstract available.
citation: Lund EK, Harvey LJ, Ladha S, Clark DC, Johnson IT. Effects of dietary fish oil supplementation on the phospholipid composition and fluidity of cell membranes from human volunteers. Ann Nutr Metab. 1999;43(5):290-300. doi: 10.1159/000012797.
citation: Marangoni F, Angeli MT, Colli S, Eligini S, Tremoli E, Sirtori CR, Galli C. Changes of n-3 and n-6 fatty acids in plasma and circulating cells of normal subjects, after prolonged administration of 20:5 (EPA) and 22:6 (DHA) ethyl esters and prolonged washout. Biochim Biophys Acta. 1993 Dec 2;1210(1):55-62. doi: 10.1016/0005-2760(93)90049-f.
citation: Marchioli R, Barzi F, Bomba E, Chieffo C, Di Gregorio D, Di Mascio R, Franzosi MG, Geraci E, Levantesi G, Maggioni AP, Mantini L, Marfisi RM, Mastrogiuseppe G, Mininni N, Nicolosi GL, Santini M, Schweiger C, Tavazzi L, Tognoni G, Tucci C, Valagussa F; GISSI-Prevenzione Investigators. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation. 2002 Apr 23;105(16):1897-903. doi: 10.1161/01.cir.0000014682.14181.f2.
citation: Marsen TA, Pollok M, Oette K, Baldamus CA. Pharmacokinetics of omega-3-fatty acids during ingestion of fish oil preparations. Prostaglandins Leukot Essent Fatty Acids. 1992 Jul;46(3):191-6. doi: 10.1016/0952-3278(92)90069-u.
citation: McDowell EM, Trump BF. Histologic fixatives suitable for diagnostic light and electron microscopy. Arch Pathol Lab Med. 1976 Aug;100(8):405-14.
citation: Nestel P, Shige H, Pomeroy S, Cehun M, Abbey M, Raederstorff D. The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid increase systemic arterial compliance in humans. Am J Clin Nutr. 2002 Aug;76(2):326-30. doi: 10.1093/ajcn/76.2.326.
citation: Obeidat WM. Recent patents review in microencapsulation of pharmaceuticals using the emulsion solvent removal methods. Recent Pat Drug Deliv Formul. 2009 Nov;3(3):178-92. doi: 10.2174/187221109789105612.
citation: Radaelli A, Cazzaniga M, Viola A, Balestri G, Janetti MB, Signorini MG, Castiglioni P, Azzellino A, Mancia G, Ferrari AU. Enhanced baroreceptor control of the cardiovascular system by polyunsaturated Fatty acids in heart failure patients. J Am Coll Cardiol. 2006 Oct 17;48(8):1600-6. doi: 10.1016/j.jacc.2006.05.073. Epub 2006 Sep 26.
citation: Rusca A, Di Stefano AF, Doig MV, Scarsi C, Perucca E. Relative bioavailability and pharmacokinetics of two oral formulations of docosahexaenoic acid/eicosapentaenoic acid after multiple-dose administration in healthy volunteers. Eur J Clin Pharmacol. 2009 May;65(5):503-10. doi: 10.1007/s00228-008-0605-4. Epub 2009 Jan 16.
citation: Raatz SK, Redmon JB, Wimmergren N, Donadio JV, Bibus DM. Enhanced absorption of n-3 fatty acids from emulsified compared with encapsulated fish oil. J Am Diet Assoc. 2009 Jun;109(6):1076-81. doi: 10.1016/j.jada.2009.03.006.
citation: Skou HA, Toft E, Christensen JH, Hansen JB, Dyerberg J, Schmidt EB. N-3 fatty acids and cardiac function after myocardial infarction in Denmark. Int J Circumpolar Health. 2001 Aug;60(3):360-5.
citation: Vidgren HM, Agren JJ, Schwab U, Rissanen T, Hanninen O, Uusitupa MI. Incorporation of n-3 fatty acids into plasma lipid fractions, and erythrocyte membranes and platelets during dietary supplementation with fish, fish oil, and docosahexaenoic acid-rich oil among healthy young men. Lipids. 1997 Jul;32(7):697-705. doi: 10.1007/s11745-997-0089-x.
citation: Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J. n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J Clin Nutr. 2006 Jul;84(1):5-17. doi: 10.1093/ajcn/84.1.5.