RACHEL: Restenosis in Coronary Stents And Cutaneous HEaLing

Sponsor

Fundación para la Investigación Biosanitaria del Principado de Asturias (Other)

Overall Status

Recruiting

CT.gov ID

NCT04915391

Collaborator

(none)

Enrollment

Location

56.2

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Restenosis Coronary Stent Occlusion Skin Scarring Keloid	Diagnostic Test: Skin biopsy and blood sample for inflammation markers, RNA and proteins

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:

The similarities and differences in cutaneous healing of patients with and without restenosis will be studied in the samples from the second biopsy.
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.
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 Design

Study Type:

Observational

Anticipated Enrollment :

80 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

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

Actual Study Start Date :

Apr 25, 2017

Anticipated Primary Completion Date :

May 31, 2021

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
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 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.	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.

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

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

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.
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.
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.