Restenosis in Coronary Stents And Cutaneous HEaLing

NCT ID: NCT04915391

Last Updated: 2022-11-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

80 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-04-25

Study Completion Date

2023-04-30

Brief Summary

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Case control study of patients with and without restenosis to demonstrate the link between in-stent restenosis and an excessive skin healing. Patients will undergo skin biopsy and blood sample tests to search for a relationship between both processes and for the identification of biomarkers and therapeutic targets.

Detailed Description

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Restenosis represents an excessive response to the coronary stent. On the other hand, skin healing with keloid formation is also an excessive repair response. There is evidence that both processes may be related because they share mechanisms mediated by inflammatory response. The purpose is to demonstrate the correlation between them for the identification of biomarkers and therapeutic targets.

The project is a case-control study with 2 groups of patients: a control group of 40 patients with ≥1 bare metal stent which in a posterior catheterization performed by clinical follow-up had no restenosis and a group of 20 patients with ≥1 bare metal stent and 20 patients with ≥1 drug eluting stent which had restenosis in a posterior catheterization also performed by clinical follow-up.

A skin biopsy will be performed at the baseline visit from which primary cell cultures of fibroblasts and keratinocytes will be obtained. Four to six weeks later a second biopsy on the scar will be performed and analyzed anatomically and pathologically. In addition, at the initial visit, blood samples will be drawn for analysis of inflammation markers, RNA and proteins. Studies can be performed at 3 levels:

1. The similarities and differences in cutaneous healing of patients with and without restenosis will be studied in the samples from the second biopsy.
2. With the cell culture from the first biopsy, the investigators will analyze the response of cutaneous cells to antiproliferative drugs and the potential advantage of vitamin D in inhibiting restenosis.
3. With the blood samples the investigators will analyze inflammatory factors, RNA and proteins that can predict these processes and that, in addition, can become potential therapeutic targets which might reduce the rate of restenosis.

Conditions

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Coronary Restenosis Coronary Stent Occlusion Skin Scarring Keloid

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Group of controls

Control group of 40 patients with ≥1 bare metal stent which in a posterior catheterization performed by clinical follow-up had no restenosis

Skin biopsy and blood sample for inflammation markers, RNA and proteins

Intervention Type DIAGNOSTIC_TEST

A skin biopsy will be performed at the baseline visit from which primary cell cultures of fibroblasts and keratinocytes will be obtained. Four to six weeks later a second biopsy on the scar will be performed and analyzed anatomically and pathologically. In addition, at the initial visit, blood samples will be drawn for analysis of inflammation markers, RNA and proteins.

Group of cases

Group of cases with 20 patients with ≥1 bare metal stent and 20 patients with ≥1 drug eluting stent which had restenosis in a posterior catheterization performed by clinical follow-up.

Skin biopsy and blood sample for inflammation markers, RNA and proteins

Intervention Type DIAGNOSTIC_TEST

A skin biopsy will be performed at the baseline visit from which primary cell cultures of fibroblasts and keratinocytes will be obtained. Four to six weeks later a second biopsy on the scar will be performed and analyzed anatomically and pathologically. In addition, at the initial visit, blood samples will be drawn for analysis of inflammation markers, RNA and proteins.

Interventions

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Skin biopsy and blood sample for inflammation markers, RNA and proteins

A skin biopsy will be performed at the baseline visit from which primary cell cultures of fibroblasts and keratinocytes will be obtained. Four to six weeks later a second biopsy on the scar will be performed and analyzed anatomically and pathologically. In addition, at the initial visit, blood samples will be drawn for analysis of inflammation markers, RNA and proteins.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Patients with previous coronary stent implantation and a posterior catheterization performed \> 8 months after the index procedure due to clinical follow-up (those ones with bare metal stents without restenosis will be included in the group of controls and those with restenosis will be included in the group of cases, 20 with bare metal and 20 with drug eluting stents).
* Age 18-75 years.

Exclusion Criteria

* Patients on chronic anti-inflammatory treatment, including corticosteroids.
* Patients with previous or current history of malignancy or any other disease mediated by inflammation.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fundación para la Investigación Biosanitaria del Principado de Asturias

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Iñigo Lozano, MD, PHD

Role: PRINCIPAL_INVESTIGATOR

Hospital Cabuenes

Locations

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Department of Cardiology, Hospital Cabueñes

Gijón, Principality of Asturias, Spain

Site Status

Countries

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Spain

References

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Komatsu R, Ueda M, Naruko T, Kojima A, Becker AE. Neointimal tissue response at sites of coronary stenting in humans: macroscopic, histological, and immunohistochemical analyses. Circulation. 1998 Jul 21;98(3):224-33. doi: 10.1161/01.cir.98.3.224.

Reference Type RESULT
PMID: 9697822 (View on PubMed)

Ozdol C, Turhan S, Tulunay C, Altin AT, Atmaca Y, Candemir B, Erol C. Association between proliferative scars and in-stent restenosis. J Cutan Med Surg. 2007 Nov-Dec;11(6):206-10. doi: 10.2310/7750.2007.00039.

Reference Type RESULT
PMID: 18042333 (View on PubMed)

Kornowski R, Hong MK, Tio FO, Bramwell O, Wu H, Leon MB. In-stent restenosis: contributions of inflammatory responses and arterial injury to neointimal hyperplasia. J Am Coll Cardiol. 1998 Jan;31(1):224-30. doi: 10.1016/s0735-1097(97)00450-6.

Reference Type RESULT
PMID: 9426044 (View on PubMed)

Albinsson S, Suarez Y, Skoura A, Offermanns S, Miano JM, Sessa WC. MicroRNAs are necessary for vascular smooth muscle growth, differentiation, and function. Arterioscler Thromb Vasc Biol. 2010 Jun;30(6):1118-26. doi: 10.1161/ATVBAHA.109.200873. Epub 2010 Apr 8.

Reference Type RESULT
PMID: 20378849 (View on PubMed)

Ji R, Cheng Y, Yue J, Yang J, Liu X, Chen H, Dean DB, Zhang C. MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ Res. 2007 Jun 8;100(11):1579-88. doi: 10.1161/CIRCRESAHA.106.141986. Epub 2007 May 3.

Reference Type RESULT
PMID: 17478730 (View on PubMed)

Sato T, Iwasaki Y, Kikkawa Y, Fukagawa M. An efficacy of intensive vitamin D delivery to neointimal hyperplasia in recurrent vascular access stenosis. J Vasc Access. 2016 Jan-Feb;17(1):72-7. doi: 10.5301/jva.5000469. Epub 2015 Sep 30.

Reference Type RESULT
PMID: 26429127 (View on PubMed)

Inoue T, Sata M, Hikichi Y, Sohma R, Fukuda D, Uchida T, Shimizu M, Komoda H, Node K. Mobilization of CD34-positive bone marrow-derived cells after coronary stent implantation: impact on restenosis. Circulation. 2007 Feb 6;115(5):553-61. doi: 10.1161/CIRCULATIONAHA.106.621714. Epub 2007 Jan 29.

Reference Type RESULT
PMID: 17261663 (View on PubMed)

Hur J, Yang HM, Yoon CH, Lee CS, Park KW, Kim JH, Kim TY, Kim JY, Kang HJ, Chae IH, Oh BH, Park YB, Kim HS. Identification of a novel role of T cells in postnatal vasculogenesis: characterization of endothelial progenitor cell colonies. Circulation. 2007 Oct 9;116(15):1671-82. doi: 10.1161/CIRCULATIONAHA.107.694778. Epub 2007 Oct 1.

Reference Type RESULT
PMID: 17909106 (View on PubMed)

Rodrigues-Diez R, Lavoz C, Carvajal G, Rayego-Mateos S, Rodrigues Diez RR, Ortiz A, Egido J, Mezzano S, Ruiz-Ortega M. Gremlin is a downstream profibrotic mediator of transforming growth factor-beta in cultured renal cells. Nephron Exp Nephrol. 2012;122(1-2):62-74. doi: 10.1159/000346575. Epub 2013 Mar 14.

Reference Type RESULT
PMID: 23548835 (View on PubMed)

Maciel TT, Melo RS, Schor N, Campos AH. Gremlin promotes vascular smooth muscle cell proliferation and migration. J Mol Cell Cardiol. 2008 Feb;44(2):370-9. doi: 10.1016/j.yjmcc.2007.10.021. Epub 2007 Nov 12.

Reference Type RESULT
PMID: 18086474 (View on PubMed)

Ravelli C, Mitola S, Corsini M, Presta M. Involvement of alphavbeta3 integrin in gremlin-induced angiogenesis. Angiogenesis. 2013 Jan;16(1):235-43. doi: 10.1007/s10456-012-9309-6. Epub 2012 Sep 30.

Reference Type RESULT
PMID: 23053782 (View on PubMed)

Lozano I, Bangueses R, Rodriguez I, Pevida M, Rodriguez-Aguilar R, Rodriguez D, Espasandin-Arias M, Llames S, Meana A, Suarez A, Rodriguez-Carrio J. In-stent restenosis is associated with proliferative skin healing and specific immune and endothelial cell profiles: results from the RACHEL trial. Front Immunol. 2023 May 31;14:1138247. doi: 10.3389/fimmu.2023.1138247. eCollection 2023.

Reference Type DERIVED
PMID: 37325628 (View on PubMed)

Other Identifiers

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RACHEL

Identifier Type: -

Identifier Source: org_study_id

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