Restenosis in Coronary Stents And Cutaneous HEaLing

NCT04915391 | Unknown

• 1 other identifier: RACHEL
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Coronary Restenosis; Coronary Stent Occlusion; Skin Scarring; Keloid

Keywords

Restenosis; Keloid; Hypertrophic skin scarring

Outcome Measures

Primary Outcomes (1)

• Link between in-stent restenosis and excessive skin healing

  Percentage of patients in case and control groups with hypertrophic pattern of skin healing after the first biopsy

  Through study completion, an average of 1 year

Secondary Outcomes (3)

• Response of skin cells to antiproliferative drugs

  Through study completion, an average of 1 year

• Circulating microRNA profile

  Through study completion, an average of 1 year

• Blood levels of immune cell subsets related to vascular repair and endothelial damage, including antiogenic T-cells, immunosenescent T-cells, monocyte subsets and low-density granulocytes.

  Through study completion, an average of 1 year

Study Arms (2)

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

Diagnostic Test: Skin biopsy and blood sample for 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.

Diagnostic Test: Skin biopsy and blood sample for inflammation markers, RNA and proteins

Interventions

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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients 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).

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Fundación para la Investigación Biosanitaria del Principado de Asturias: lead

Study Sites (1)

Department of Cardiology, Hospital Cabueñes

Gijón, Principality of Asturias, 33203, Spain

Location

Related Publications (12)

• 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.

  PMID: 9697822 RESULT

• 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.

  PMID: 18042333 RESULT

• 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.

  PMID: 9426044 RESULT

• 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.

  PMID: 20378849 RESULT

• 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.

  PMID: 17478730 RESULT

• 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.

  PMID: 26429127 RESULT

• 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.

  PMID: 17261663 RESULT

• 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.

  PMID: 17909106 RESULT

• 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.

  PMID: 23548835 RESULT

• 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.

  PMID: 18086474 RESULT

• 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.

  PMID: 23053782 RESULT

• 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.

  PMID: 37325628 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Two skin biopsies of the shoulder and blood samples

MeSH Terms

Conditions

Coronary Restenosis; Cicatrix; Keloid

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Coronary Stenosis; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Iñigo Lozano, MD, PHD

  Hospital Cabuenes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2021
• First Posted: June 7, 2021
• Study Start: April 25, 2017
• Primary Completion: December 31, 2022
• Study Completion: April 30, 2023
• Last Updated: November 21, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)