Arterial Imaging of Inflammation and Resolution After Endovascular Surgery

Peripheral Arterial Disease Clinical Trial

— AIIRES  

Official title:

Arterial Imaging of Inflammation and Resolution After Endovascular Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03590769
• Other study ID #: 16-21018
• Status: Completed
• Phase: Phase 1
• Start date: June 1, 2017
• Est. completion date: September 3, 2019

Study information

• Verified date: November 2020
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates the local inflammatory and resolution response of patients undergoing peripheral vascular intervention like an angioplasty of the superficial femoral artery (SFA) or popliteal artery, or stenting of the iliac artery or SFA, through the use of Positron emission tomography-magnetic resonance imaging (PET/MRI). PET/MRI will be performed prior to intervention, one day and one week after intervention.

Description:

Magnetic resonance imaging (MRI) imaging allows for non-invasive visualization of anatomical structures while Positron emission tomography (PET) scans allow for the observation of molecular and cellular activities. Using a PET/MRI in patients with vascular injury post intervention with help evaluate the vascular inflammatory and resolution response in vivo. Acute vascular injury through endovascular intervention results in recruitment of inflammatory cells such as macrophages to the vessel wall. Macrophages are very metabolically active and consume glucose at a high rate. In PET/MRI, subjects are injected with 18F-Fluorodeoxyglucose (18F-FDG), a radioactively labeled glucose molecule which is consumed by macrophages. When 18F-FDG is consumed, it is retained within macrophages more avidly than other atherosclerotic lesion elements. Thus, FDG-PET provides a unique and noninvasive approach to quantitatively measure macrophage activity at the intervention site. This study will provide key pilot data for developing an imaging surrogate endpoint for pro-resolving mediator treatment intervention trials going forward.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: September 3, 2019
• Est. primary completion date: September 3, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Over the age of 40,
• With resting or exercise ABI <0.9, TBI <0.6
• Have claudication or limb threatening ischemia & planning to undergo a percutaneous angioplasty of SFA or popliteal artery, or stenting of the iliac artery or SFA.

Exclusion Criteria:

• Evidence of active infection
• Hypersensitivity or allergy to contrast agents
• Chronic liver disease, renal disease (GFR< 30) or chronic inflammatory disorders
• Insulin dependent diabetes
• Presence of metal within subject's body, pacemakers, or defibrillators
• 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

Related Conditions & MeSH terms

• Calcinosis
• Claudication
• Claudication, Intermittent
• Iliac Artery Disease
• Inflammation
• Intermittent Claudication
• PAD
• Peripheral Arterial Disease
• Peripheral Vascular Diseases
• SFA - Superficial Femoral Artery Stenosis
• Vascular Calcification

Intervention

Drug:
• 18F-FDG
All subject will undergo PET/MRI scans pre-operatively, 1 day and 1 week post-operatively using FDG

Locations

Country	Name	City	State
United States	San Francisco General Hospital	San Francisco	California
United States	UCSF	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

References & Publications (36)

Alie N, Eldib M, Fayad ZA, Mani V. Inflammation, Atherosclerosis, and Coronary Artery Disease: PET/CT for the Evaluation of Atherosclerosis and Inflammation. Clin Med Insights Cardiol. 2015 Jan 7;8(Suppl 3):13-21. doi: 10.4137/CMC.S17063. eCollection 2014. Review. — View Citation

Almagor M, Keren A, Banai S. Increased C-reactive protein level after coronary stent implantation in patients with stable coronary artery disease. Am Heart J. 2003 Feb;145(2):248-53. — View Citation

Armstrong EJ, Chen DC, Westin GG, Singh S, McCoach CE, Bang H, Yeo KK, Anderson D, Amsterdam EA, Laird JR. Adherence to guideline-recommended therapy is associated with decreased major adverse cardiovascular events and major adverse limb events among patients with peripheral arterial disease. J Am Heart Assoc. 2014 Apr 10;3(2):e000697. doi: 10.1161/JAHA.113.000697. — View Citation

Beckman JA, Preis O, Ridker PM, Gerhard-Herman M. Comparison of usefulness of inflammatory markers in patients with versus without peripheral arterial disease in predicting adverse cardiovascular outcomes (myocardial infarction, stroke, and death). Am J Cardiol. 2005 Nov 15;96(10):1374-8. Epub 2005 Sep 27. — View Citation

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

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

Fowkes FG, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, Norman PE, Sampson UK, Williams LJ, Mensah GA, Criqui MH. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013 Oct 19;382(9901):1329-40. doi: 10.1016/S0140-6736(13)61249-0. Epub 2013 Aug 1. Review. — 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

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

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

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

Rudd JH, Myers KS, Bansilal S, Machac J, Pinto CA, Tong C, Rafique A, Hargeaves R, Farkouh M, Fuster V, Fayad ZA. Atherosclerosis inflammation imaging with 18F-FDG PET: carotid, iliac, and femoral uptake reproducibility, quantification methods, and recommendations. J Nucl Med. 2008 Jun;49(6):871-8. doi: 10.2967/jnumed.107.050294. Epub 2008 May 15. — 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

van der Valk FM, Verweij SL, Zwinderman KA, Strang AC, Kaiser Y, Marquering HA, Nederveen AJ, Stroes ES, Verberne HJ, Rudd JH. Thresholds for Arterial Wall Inflammation Quantified by (18)F-FDG PET Imaging: Implications for Vascular Interventional Studies. JACC Cardiovasc Imaging. 2016 Oct;9(10):1198-1207. doi: 10.1016/j.jcmg.2016.04.007. Epub 2016 Sep 14. — 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):674-81. doi: 10.1194/jlr.P055418. Epub 2015 Jan 23. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes found in the quantitative measure of FDG-PET uptake at intervention site prior to and after peripheral vascular injury.	Patient is given 18F-FDG radio tracer. The tracer is quantitatively measured through FDG-PET imaging modality for uptake at the intervention site.	1 time each week for 3 weeks
Secondary	Changes in the correlating the inflammatory and resolution response prior to and after peripheral vascular injury.	Venipuncture of subject and collection of blood allows measures pro-inflammatory markers and targeted metabolipodimics.	1 time each week for 3 weeks