Restenosis in Coronary Stents And Cutaneous HEaLing

• Conditions: Coronary Restenosis; Skin Scarring; Coronary Stent Occlusion; Keloid
• Interventions: Diagnostic Test: Skin biopsy and blood sample for inflammation markers, RNA and proteins

• Registration Number: NCT04915391
• Lead Sponsor: Fundación para la Investigación Biosanitaria del Principado de Asturias

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.

Detailed 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.

Study Timeline

• Study Start: 2017-04-25
• Study First Submitted: 2021-03-16
• Study First Submitted QC: 2021-05-31
• Study First Posted: 2021-06-07
• Status Verified: 2022-07
• Last Update Submitted: 2022-11-16
• Last Update Posted: 2022-11-21
• Primary Completion: 2022-12-31
• Study Completion: 2023-04-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Group of controls	Skin biopsy and blood sample for inflammation markers, RNA and proteins	Control group of 40 patients with ≥1 bare metal stent which in a posterior catheterization performed by clinical follow-up had no restenosis
Group of cases	Skin biopsy and blood sample for inflammation markers, RNA and proteins	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.

Primary Outcome Measures

Name	Time	Method
Link between in-stent restenosis and excessive skin healing	Through study completion, an average of 1 year	Percentage of patients in case and control groups with hypertrophic pattern of skin healing after the first biopsy

Secondary Outcome Measures

Name	Time	Method
Response of skin cells to antiproliferative drugs	Through study completion, an average of 1 year	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.
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	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
Circulating microRNA profile	Through study completion, an average of 1 year	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.

Trial Locations

Locations (1)

Department of Cardiology, Hospital Cabueñes; 🇪🇸 Gijón, Asturias, Spain