Restenosis in Coronary Stents And Cutaneous HEaLing

Keloid Clinical Trial

— RACHEL  

Official title:

Restenosis in Coronary Stents And Cutaneous HEaling: Identification of Biochemical Markers and Potential Therapeutic Targets

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04915391
• Other study ID #: RACHEL
• Status: Active, not recruiting
• Start date: April 25, 2017
• Est. completion date: April 30, 2023

Study information

• Verified date: July 2022
• Source: Fundación para la Investigación Biosanitaria del Principado de Asturias
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: April 30, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cicatrix
• Coronary Restenosis
• Coronary Stent Occlusion
• Keloid
• Skin Scarring

Intervention

Diagnostic Test:
• 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.

Locations

Country	Name	City	State
Spain	Department of Cardiology, Hospital Cabueñes	Gijón	Asturias

Sponsors (1)

Lead Sponsor	Collaborator
Fundación para la Investigación Biosanitaria del Principado de Asturias

Country where clinical trial is conducted

Spain, 

References & Publications (11)

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 — View Citation

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 — View Citation

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. Epub 2007 Jan 29. — View Citation

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. Epub 2007 May — View Citation

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. — View Citation

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. — View Citation

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. Epub 2007 Nov 12. — View Citation

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. — View Citation

Ravelli C, Mitola S, Corsini M, Presta M. Involvement of avß3 integrin in gremlin-induced angiogenesis. Angiogenesis. 2013 Jan;16(1):235-43. doi: 10.1007/s10456-012-9309-6. Epub 2012 Sep 30. — View Citation

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 — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Response of skin cells to antiproliferative drugs	Comparison of the proliferation rate of primary skin fibroblasts, from patients of the different groups, undergoing treatment with an antiproliferative drug. The continuous variable will be the percentage of living cells at the end of the treatment with respect to the initial cells, and mean values in the groups will be statistically compared.	Through study completion, an average of 1 year
Secondary	Circulating microRNA profile	Determination of the profile and levels of circulating microRNAs in patients from the different groups. Plasma samples from some individuals in each group will be analyzed using a microarray. To assess the level of circulating microRNAs in all patients, real-time reverse transcription-polymerase chain reaction will be used. Mean values in the groups will be statistically compared.	Through study completion, an average of 1 year
Secondary	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.	These populations will be measured in samples of peripheral blood or isolated mononuclear cells by flow cytometry according to the expression of their surface markers	Through study completion, an average of 1 year