Mer-TK in Human Cardiac Cells

NCT ID: NCT04322630

Last Updated: 2021-08-12

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

COMPLETED

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-05-10

Study Completion Date

2020-12-31

Brief Summary

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The relationship between the immune system and the myocardium after myocardial ischemia is an evolving field of research. Crosstalk occurs between macrophages and cardiac myocytes to promote cardio-protection and resolution of inflammation after myocardial ischemia and reperfusion injury (MI/R injury).

Myeloid-epithelial-reproductive tyrosine kinase (MerTK), a member of the TAM family of tyrosine kinase receptors (Tyro-Axl-MerTK), is a macrophage receptor that mediates efferocytosis, anti-inflammatory signaling, and resolution of inflammation. After MI/R injury, intact MerTK is necessary for the phagocytosis of dead cardiac myocytes and to promote anti-inflammatory signaling. Proteolytic cleavage of MerTK to its inactive form, soluble MER, restricts the capacity of macrophages to phagocytize dead cardiac myocytes and impairs MerTK-dependent anti-inflammatory signaling resulting in suppressive effects on cardiac remodeling and function.

The Thorp lab at Northwestern University has previously measured soluble MER levels in both adult mice and humans and found that soluble MER concentrations increase after MI/R injury. In adult MI patients, soluble MER was measured post coronary artery reperfusion and was found to be increased (average 3200 pg/mL compared to 1700 pg/mL) compared to controls with stable cardiovascular disease. Based on murine data, the lab further postulated that reperfusion injury may directly interfere with MerTK-dependent cardiac repair as reactive oxygen species formed during reperfusion injury induce proteolytic cleavage of MerTK to soluble MER.

Myocardial infarctions are rare events in pediatric patients. However, pediatric hearts are exposed to periods of hypoperfusion, ischemia, and inflammation during times of stress such as cardiac bypass and critical illness, and it is unknown how soluble MER levels change in response to these events. Thus, I was interested in investigating how soluble MER levels change after MI/R injury induced by cardiac bypass as well as in the utility of soluble MER as a biomarker of cardiac inflammation and injury in pediatric patients.

Detailed Description

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Conditions

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Myocardial Inflammation Myocardial Infarction

Study Design

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Observational Model Type

OTHER

Study Time Perspective

OTHER

Study Groups

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Pediatric Cardiac Bypass Patients

Blood samples obtained from patients ages from birth-19 years-old as well as cyanotic and acyanotic cardiac lesions who underwent cardiac bypass.

Change in Soluble MER Concentration

Intervention Type OTHER

Measuring change in soluble MER Concentration post compared to pre bypass for each patient.

Interventions

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Change in Soluble MER Concentration

Measuring change in soluble MER Concentration post compared to pre bypass for each patient.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* All patient ages from birth-19 years-old as well as cyanotic and acyanotic cardiac lesions will be included

Exclusion Criteria

* Patients will be excluded if both pre and post bypass blood samples are not available.
Maximum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ann & Robert H Lurie Children's Hospital of Chicago

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Ann & Robert H Lurie Children's Hopsital

Chicago, Illinois, United States

Site Status

Countries

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United States

Other Identifiers

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2019-2445

Identifier Type: -

Identifier Source: org_study_id

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