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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02719665
Other study ID # 15-17371
Secondary ID
Status Completed
Phase N/A
First received
Last updated
Start date March 2016
Est. completion date December 15, 2020

Study information

Verified date May 2021
Source University of California, San Francisco
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to understand the effects of fish oil supplement (containing parts of omega-3 fatty acids) on inflammation. The investigators are aiming to identify which dose of the fish oil supplement is the most effective. The name of the fish oil supplement is "SPM Emulsion."


Description:

The OMEGA-SPM-DOSE trial and the OMEGA-SPM-PAD trial are two parts of a pilot study which aims to investigate the effect of a novel formulation of a nutritional supplement containing highly concentrated n-3 PUFA metabolites (SPM Emulsion) on the metabolo-lipidomic profile of healthy volunteers and patients with Peripheral Arterial Disease(PAD). Ten healthy volunteers and ten patients with PAD will participate in Part 1a, the "OMEGA-SPM-DOSE Study". A follow-up, placebo controlled, prospective study on the best dosing modality determined in Phase 1a will then take place in a PAD and OA population (n=12), Phase 1b - the "OMEGA-SPM-PAD Study". Specific measurements will include targeted metabolo-lipidomic profiling, established markers of inflammation, and functional monocyte and macrophage assays. The proposed studies have the potential to provide important new insights on the role of nutritional interventions in PAD.


Recruitment information / eligibility

Status Completed
Enrollment 30
Est. completion date December 15, 2020
Est. primary completion date December 15, 2020
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group N/A and older
Eligibility Inclusion Criteria: Healthy Volunteers: -Age 20-80 PAD Patients: - Mild claudication to rest pain (Rutherford 1-4) - Resting or exercise ABI < 0.9 or TBI < 0.6 - Age 40 and more OA Patients: -Lower extremity (hip or knee) OA Exclusion Criteria: PAD, OA Patients and Healthy Volunteers: - Plan to undergo surgical procedure or PVI for treatment of PAD within one month - Evidence of active infection - Hypersensitivity or allergy to fish or seafood - Already on n-3 PUFA or equivalent - Chronic liver disease, end-stage renal disease (CKD 5), or chronic inflammatory disorders - Poorly controlled diabetes (HbA1C > 8%) - BMI < 20 or >35 - Recent other major surgery or illness within 30 days - Use of immunosuppressive medications or steroids - History of organ transplantation - Pregnancy, or plans to become pregnant, or lactating Healthy Volunteers: - hsCRP > 2mg/L - Regular aspirin use - Regular non-steroidal anti-inflammatory drug use

Study Design


Intervention

Dietary Supplement:
SPM Emulsion, Dose-modality
Phase 1a Dose-Finding oral SPM administration of increasing dose (15ml, 30ml, and 60ml) by the following schedule: Days 1 to 5: 15 ml; Days 6 to 14: Washout, no SPM administration; Days 15 to 19: 30 ml; Days 20-28: Washout, no SPM administration; Days 29-33: 60 ml
SPM Softgel, Dose-Modality
Phase 1b Dose-Finding oral softtel SPM administration of two different doses (2 softgel vs 4 softgel) Days 0 to 5: 2 SPM softgel; Days 6 to 21: Washout, no SPM administration; Days 22 to 26: 4 SPM softgel; Days 27-42: Washout, no SPM administration
Placebo Softgel
Days 43-47: 4 Placebo softgel; Day 48-64 Washout

Locations

Country Name City State
United States University of California San Francisco San Francisco California

Sponsors (1)

Lead Sponsor Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

References & Publications (36)

Akagi D, Chen M, Toy R, Chatterjee A, Conte MS. Systemic delivery of proresolving lipid mediators resolvin D2 and maresin 1 attenuates intimal hyperplasia in mice. FASEB J. 2015 Jun;29(6):2504-13. doi: 10.1096/fj.14-265363. Epub 2015 Mar 16. — View Citation

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Brevetti G, Silvestro A, Di Giacomo S, Bucur R, Di Donato A, Schiano V, Scopacasa F. Endothelial dysfunction in peripheral arterial disease is related to increase in plasma markers of inflammation and severity of peripheral circulatory impairment but not to classic risk factors and atherosclerotic burden. J Vasc Surg. 2003 Aug;38(2):374-9. — View Citation

Busti C, Falcinelli E, Momi S, Gresele P. Matrix metalloproteinases and peripheral arterial disease. Intern Emerg Med. 2010 Feb;5(1):13-25. doi: 10.1007/s11739-009-0283-y. Epub 2009 Jul 21. Review. Erratum in: Intern Emerg Med. 2010 Feb;5(1):89. — View Citation

Carriere I, Dupuy AM, Lacroux A, Cristol JP, Delcourt C; Pathologies Oculaires Liées à l'Age Study Group. Biomarkers of inflammation and malnutrition associated with early death in healthy elderly people. J Am Geriatr Soc. 2008 May;56(5):840-6. doi: 10.1111/j.1532-5415.2008.01677.x. Epub 2008 Apr 9. — View Citation

Chatterjee A, Sharma A, Chen M, Toy R, Mottola G, Conte MS. The pro-resolving lipid mediator maresin 1 (MaR1) attenuates inflammatory signaling pathways in vascular smooth muscle and endothelial cells. PLoS One. 2014 Nov 19;9(11):e113480. doi: 10.1371/journal.pone.0113480. eCollection 2014. — View Citation

Chiang N, Fredman G, Bäckhed F, Oh SF, Vickery T, Schmidt BA, Serhan CN. Infection regulates pro-resolving mediators that lower antibiotic requirements. Nature. 2012 Apr 25;484(7395):524-8. doi: 10.1038/nature11042. — View Citation

Conen D, Rexrode KM, Creager MA, Ridker PM, Pradhan AD. Metabolic syndrome, inflammation, and risk of symptomatic peripheral artery disease in women: a prospective study. Circulation. 2009 Sep 22;120(12):1041-7. doi: 10.1161/CIRCULATIONAHA.109.863092. Epub 2009 Sep 8. — View Citation

Criqui MH, Ho LA, Denenberg JO, Ridker PM, Wassel CL, McDermott MM. Biomarkers in peripheral arterial disease patients and near- and longer-term mortality. J Vasc Surg. 2010 Jul;52(1):85-90. doi: 10.1016/j.jvs.2010.02.004. Epub 2010 May 14. — View Citation

Goodney PP, Beck AW, Nagle J, Welch HG, Zwolak RM. National trends in lower extremity bypass surgery, endovascular interventions, and major amputations. J Vasc Surg. 2009 Jul;50(1):54-60. doi: 10.1016/j.jvs.2009.01.035. Epub 2009 May 28. — View Citation

Grenon SM, Conte MS, Nosova E, Alley H, Chong K, Harris WS, Vittinghoff E, Owens CD. Association between n-3 polyunsaturated fatty acid content of red blood cells and inflammatory biomarkers in patients with peripheral artery disease. J Vasc Surg. 2013 Nov;58(5):1283-90. doi: 10.1016/j.jvs.2013.05.024. Epub 2013 Jul 2. — View Citation

Grenon SM, Owens CD, Alley H, Chong K, Yen PK, Harris W, Hughes-Fulford M, Conte MS. n-3 Polyunsaturated fatty acids supplementation in peripheral artery disease: the OMEGA-PAD trial. Vasc Med. 2013 Oct;18(5):263-74. doi: 10.1177/1358863X13503695. Epub 2013 Sep 19. — View Citation

Grenon SM, Owens CD, Nosova EV, Hughes-Fulford M, Alley HF, Chong K, Perez S, Yen PK, Boscardin J, Hellmann J, Spite M, Conte MS. Short-Term, High-Dose Fish Oil Supplementation Increases the Production of Omega-3 Fatty Acid-Derived Mediators in Patients With Peripheral Artery Disease (the OMEGA-PAD I Trial). J Am Heart Assoc. 2015 Aug 21;4(8):e002034. doi: 10.1161/JAHA.115.002034. — View Citation

Havelka GE, Kibbe MR. The vascular adventitia: its role in the arterial injury response. Vasc Endovascular Surg. 2011 Jul;45(5):381-90. doi: 10.1177/1538574411407698. Epub 2011 May 13. Review. — View Citation

Ho KJ, Spite M, Owens CD, Lancero H, Kroemer AH, Pande R, Creager MA, Serhan CN, Conte MS. Aspirin-triggered lipoxin and resolvin E1 modulate vascular smooth muscle phenotype and correlate with peripheral atherosclerosis. Am J Pathol. 2010 Oct;177(4):2116-23. doi: 10.2353/ajpath.2010.091082. Epub 2010 Aug 13. — View Citation

Hudert CA, Weylandt KH, Lu Y, Wang J, Hong S, Dignass A, Serhan CN, Kang JX. Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis. Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11276-81. Epub 2006 Jul 17. — View Citation

Inoue T, Croce K, Morooka T, Sakuma M, Node K, Simon DI. Vascular inflammation and repair: implications for re-endothelialization, restenosis, and stent thrombosis. JACC Cardiovasc Interv. 2011 Oct;4(10):1057-66. doi: 10.1016/j.jcin.2011.05.025. Review. — View Citation

Mahoney EM, Wang K, Keo HH, Duval S, Smolderen KG, Cohen DJ, Steg G, Bhatt DL, Hirsch AT; Reduction of Atherothrombosis for Continued Health (REACH) Registry Investigators. Vascular hospitalization rates and costs in patients with peripheral artery disease in the United States. Circ Cardiovasc Qual Outcomes. 2010 Nov;3(6):642-51. doi: 10.1161/CIRCOUTCOMES.109.930735. Epub 2010 Oct 12. — View Citation

Miyahara T, Runge S, Chatterjee A, Chen M, Mottola G, Fitzgerald JM, Serhan CN, Conte MS. D-series resolvin attenuates vascular smooth muscle cell activation and neointimal hyperplasia following vascular injury. FASEB J. 2013 Jun;27(6):2220-32. doi: 10.1096/fj.12-225615. Epub 2013 Feb 13. — View Citation

Mizwicki MT, Liu G, Fiala M, Magpantay L, Sayre J, Siani A, Mahanian M, Weitzman R, Hayden EY, Rosenthal MJ, Nemere I, Ringman J, Teplow DB. 1a,25-dihydroxyvitamin D3 and resolvin D1 retune the balance between amyloid-ß phagocytosis and inflammation in Alzheimer's disease patients. J Alzheimers Dis. 2013;34(1):155-70. doi: 10.3233/JAD-121735. — View Citation

Oh SF, Pillai PS, Recchiuti A, Yang R, Serhan CN. Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation. J Clin Invest. 2011 Feb;121(2):569-81. doi: 10.1172/JCI42545. Epub 2011 Jan 4. — View Citation

Owens CD, Ridker PM, Belkin M, Hamdan AD, Pomposelli F, Logerfo F, Creager MA, Conte MS. Elevated C-reactive protein levels are associated with postoperative events in patients undergoing lower extremity vein bypass surgery. J Vasc Surg. 2007 Jan;45(1):2-9; discussion 9. Epub 2006 Nov 21. — View Citation

Owens CD, Wake N, Conte MS, Gerhard-Herman M, Beckman JA. In vivo human lower extremity saphenous vein bypass grafts manifest flow mediated vasodilation. J Vasc Surg. 2009 Nov;50(5):1063-70. doi: 10.1016/j.jvs.2009.06.022. Epub 2009 Aug 12. — View Citation

Pande RL, Perlstein TS, Beckman JA, Creager MA. Secondary prevention and mortality in peripheral artery disease: National Health and Nutrition Examination Study, 1999 to 2004. Circulation. 2011 Jul 5;124(1):17-23. doi: 10.1161/CIRCULATIONAHA.110.003954. Epub 2011 Jun 20. — View Citation

Recchiuti A, Codagnone M, Pierdomenico AM, Rossi C, Mari VC, Cianci E, Simiele F, Gatta V, Romano M. Immunoresolving actions of oral resolvin D1 include selective regulation of the transcription machinery in resolution-phase mouse macrophages. FASEB J. 2014 Jul;28(7):3090-102. doi: 10.1096/fj.13-248393. Epub 2014 Apr 1. — View Citation

Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease. Circulation. 1998 Feb 10;97(5):425-8. — View Citation

Ridker PM, Stampfer MJ, Rifai N. Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA. 2001 May 16;285(19):2481-5. — View Citation

Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999 Jan 14;340(2):115-26. Review. — View Citation

Sachs T, Pomposelli F, Hamdan A, Wyers M, Schermerhorn M. Trends in the national outcomes and costs for claudication and limb threatening ischemia: angioplasty vs bypass graft. J Vasc Surg. 2011 Oct;54(4):1021-1031.e1. doi: 10.1016/j.jvs.2011.03.281. Epub 2011 Aug 31. — View Citation

Schillinger M, Exner M, Mlekusch W, Rumpold H, Ahmadi R, Sabeti S, Haumer M, Wagner O, Minar E. Vascular inflammation and percutaneous transluminal angioplasty of the femoropopliteal artery: association with restenosis. Radiology. 2002 Oct;225(1):21-6. — View Citation

Serhan CN, Yang R, Martinod K, Kasuga K, Pillai PS, Porter TF, Oh SF, Spite M. Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions. J Exp Med. 2009 Jan 16;206(1):15-23. doi: 10.1084/jem.20081880. Epub 2008 Dec 22. — View Citation

Serhan CN. Pro-resolving lipid mediators are leads for resolution physiology. Nature. 2014 Jun 5;510(7503):92-101. doi: 10.1038/nature13479. Review. — View Citation

Serhan CN. Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu Rev Immunol. 2007;25:101-37. Review. — View Citation

Tzoulaki I, Murray GD, Lee AJ, Rumley A, Lowe GD, Fowkes FG. C-reactive protein, interleukin-6, and soluble adhesion molecules as predictors of progressive peripheral atherosclerosis in the general population: Edinburgh Artery Study. Circulation. 2005 Aug 16;112(7):976-83. Epub 2005 Aug 8. — View Citation

Vidula H, Tian L, Liu K, Criqui MH, Ferrucci L, Pearce WH, Greenland P, Green D, Tan J, Garside DB, Guralnik J, Ridker PM, Rifai N, McDermott MM. Biomarkers of inflammation and thrombosis as predictors of near-term mortality in patients with peripheral arterial disease: a cohort study. Ann Intern Med. 2008 Jan 15;148(2):85-93. — View Citation

Wang X, Hjorth E, Vedin I, Eriksdotter M, Freund-Levi Y, Wahlund LO, Cederholm T, Palmblad J, Schultzberg M. Effects of n-3 FA supplementation on the release of proresolving lipid mediators by blood mononuclear cells: the OmegAD study. J Lipid Res. 2015 Mar;56(3):674-681. doi: 10.1194/jlr.P055418. Epub 2015 Jan 23. — View Citation

* Note: There are 36 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Optimal Phase 1b Dose The smallest dose administered in Phase 1a participants which results in an increase in Resolution Index at least 3 times that of baseline, or the subsequent larger dose resulting in a Resolution Index greater than 2 times that of the preceding does with no increase in side effects at the larger dose. Baseline, Day 33
Primary Change in the Resolution Index Integrated metabolo-lipidomics assessment of SPM pathways: Average concentration of 15-HEPE, 18-HEPE, 4-HDHA, and 17-HDHA in plasma. Baseline, Day 5
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