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Immunometabolic Pattern of Intermittent Hypoxia During ST-segment Elevation Myocardial Infarction

Primary Purpose

Myocardial Ischemic-reperfusion Injury

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Remote Ischemic Conditioning (RIC)
Sponsored by
Clinical Hospital Center Rijeka
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Myocardial Ischemic-reperfusion Injury

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

For group 1:

  1. Acute coronary syndrome; angina pectoris (chest pain with negative troponin T with or without changes in electrocardiographic findings);
  2. Monovascular disease, preocclusive stenosis with TIMI(thrombolysis in myocardial infarction) > 1 on the left main or anterior descending branch of the left coronary artery
  3. Visually estimated diameter of the epicardial coronary artery from 2.5 mm to 4.0 mm

For group 2:

  1. Acute myocardial infarction with ST-segment elevation (ST-segment elevation> 0.1 mV in two or more leads, or> 0.2 mV in V1-V3) <6 hours from the onset of chest pain
  2. Symptoms of angina pectoris preceding acute myocardial infarction
  3. Monovascular disease, occlusion or preocclusive stenosis of the anterior descending branch of the left coronary artery with TIMI <1 flow in STEMI;
  4. After opening the artery and setting the stent TIMI> 2 flow
  5. Visually estimated epicardial coronary artery diameter up to 2.5 mm to 4.0 mm

For groups 3 and 4:

  1. Acute myocardial infarction with ST-segment elevation (ST-segment elevation> 0.1 mV in two or more leads, or> 0.2 mV in V1-V3) <6 hours from the onset of chest pain
  2. No symptoms of angina pectoris preceding acute myocardial infarction
  3. Monovascular disease, occlusion or preocclusive stenosis of the anterior descending branch of the left coronary artery with TIMI <1 flow in STEMI;
  4. After opening the artery and stent placement TIMI> 2 flow
  5. Visually estimated diameter of the epicardial coronary artery from 2.5 mm to 4.0 mm

For all groups:

  1. Age of patients over 18 years
  2. Signed written informed consent to be included in the survey

Exclusion Criteria:

  1. Cardiac arrest before or after PCI;
  2. Cardiogenic shock;
  3. Previous myocardial infarction or revascularization of the heart;
  4. Anginal pain before the onset of STEMI in patients to be subjected to RIC;
  5. Patients with end-stage renal or hepatic disease, diabetics with developed micro and macrovascular complications, oncology patients;
  6. Significant collaterals in the area of the occluded artery (Rentrop gradus> 1);
  7. Previous use of nitrates and corticosteroids;
  8. Pregnant or breastfeeding women;
  9. Iodine allergy (contrast media);
  10. Increase in body temperature > 37.5 ° C
  11. Participation in another clinical trial

Randomly selected (coin toss) patients will be randomized to group 3 and 4, respectively, for percutaneous coronary intervention with or without RIC

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm Type

    No Intervention

    No Intervention

    Active Comparator

    No Intervention

    Active Comparator

    Arm Label

    Group 1- angina pectoris

    Group 2 - angina pectoris + STEMI+ PCI

    Group 3 - without angina pectoris + STEMi + RIC + PCI

    Group 4 - without angina pectoris + STEMI + PCI

    Group 5 - healthy + RIC

    Arm Description

    Patients with acute coronary syndrome; angina pectoris (chest pain with negative troponin T with or without changes in electrocardiographic findings);

    Patients with acute myocardial infarction with ST-segment elevation, < 6 hours from the onset of chest pain and preceding symptoms of angina pectoris with primary percutaneous coronary intervention.

    Patients with acute myocardial infarction with ST-segment elevation, < 6 hours from the onset of chest pain and without preceding symptoms of angina pectoris with primary percutaneous coronary intervention during which it's carried out remote ischemic conditioning (RIC)

    Patients with acute myocardial infarction with ST-segment elevation, < 6 hours from the onset of chest pain and without preceding symptoms of angina pectoris with primary percutaneous coronary intervention.

    healthy volunteers of the same age and sex, whose samples will be taken after the RIC procedure

    Outcomes

    Primary Outcome Measures

    Measurement of the concentration and dynamics of troponin T (Trop T)
    Serum concentrations (ng/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Measurement of the concentration and dynamics of cardiac myosin binding protein C (cMyBP-C)
    Serum concentrations (ng/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Measurement of the concentration and dynamics of creatine kinase-MB (CK-MB)
    Serum concentrations (ng/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Measurement of the concentration and dynamics of oxidation/mitochondrial parameter, hypoxia-induced factor 1 alpha (HIF 1α)
    serum concentrations (pg/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Measurement of the concentration and dynamics of metabolic parameter, glycine
    Serum concentrations (μmol/l) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Measurement of the concentration and dynamics of metabolic parameter, kynurenine
    Serum concentrations (μmol/l) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Measurement of the concentration and dynamics of metabolic parameter, succinate
    Serum concentrations (μM) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Measurement of the concentration and dynamics of immunological parameter, interleukin 1 beta (IL-1 beta)
    Serum concentrations (pg/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Measurement of the concentration and dynamics of immunological parameter, transforming growth factor beta (TGF beta)
    Serum concentrations (ng/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Measurement of the concentration and dynamics of immunological parameter, monocyte chemoattraction protein 1 (MCP-1)
    Serum concentrations (pg/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.

    Secondary Outcome Measures

    The changes in serum values of immunometabolic parameters and creatine kinase-MB
    The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with a degree of tissue damage creatine kinase-MB.
    The changes in serum values of immunometabolic parameters and troponin T
    The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with a degree of tissue damage troponin T
    The changes in serum values of immunometabolic parameters and left heart ejection fraction
    The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with functional assessment of the heart muscle, ejection fraction (%).
    The changes in serum values of immunometabolic parameters in PCI groups and angina pectoris (AP) group
    The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with the data of patients diagnosed with angina pectoris (AP).
    The changes in serum values of immunometabolic parameters in PCI groups and the group of healthy volunteers
    The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with the group of healthy volunteers in whom the RIC method was used.

    Full Information

    First Posted
    January 12, 2022
    Last Updated
    January 28, 2022
    Sponsor
    Clinical Hospital Center Rijeka
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05230966
    Brief Title
    Immunometabolic Pattern of Intermittent Hypoxia During ST-segment Elevation Myocardial Infarction
    Official Title
    Immunometabolic Pattern of Intermittent Hypoxia as a Protective Mechanism Against Lethal Reperfusion Injury in Patients With ST-segment Elevation Myocardial Infarction
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    February 1, 2022 (Anticipated)
    Primary Completion Date
    December 1, 2022 (Anticipated)
    Study Completion Date
    March 2, 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Clinical Hospital Center Rijeka

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The aim of this study is to characterize the protective pattern of intermittent hypoxia, angina pectoris and remote ischemic conditioning, in reperfusion injury by determining and monitoring the plasma immunometabolic parameters of patients with STEMI. This could contribute to better understanding of this phenotypic pattern with translation into clinical practice.
    Detailed Description
    In acute myocardial infarction with ST segment elevation (STEMI), lethal reperfusion injury of the myocardium, caused by percutaneous coronary intervention (PCI), represents additional and irreversible damage due to ischemic heart muscle reperfusion that contributes to the final size of the infarct zone by up to 50%. The size of the infarcted area is the major determinant for the long-term prognosis and heart failure progression in patients with STEMI. Cardioprotection from ischemic - reperfusion myocardial injury (MIRI) can be regulated by its own innate physiological adaptive mechanisms like intermittent hypoxia achieved by the method of conditioning that includes short sublethal ischemic and reperfusion episodes. The known natural clinical equivalent of intermittent hypoxia and the starting point in understanding the underlying mechanism is angina pectoris (AP). Intermittent hypoxia is a protective mechanism against heart ischemic-reperfusion injury with reduced tissue damage and consequently better outcome in patients with STEMI. For the purpose of this work, a cardioprotective pattern was defined that includes immunometabolic factors as parameters for assessing the state of intermittent hypoxia on which the success of the application of the method of remote ischemic conditioning (RIC) is based.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Myocardial Ischemic-reperfusion Injury

    7. Study Design

    Primary Purpose
    Other
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    25 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Group 1- angina pectoris
    Arm Type
    No Intervention
    Arm Description
    Patients with acute coronary syndrome; angina pectoris (chest pain with negative troponin T with or without changes in electrocardiographic findings);
    Arm Title
    Group 2 - angina pectoris + STEMI+ PCI
    Arm Type
    No Intervention
    Arm Description
    Patients with acute myocardial infarction with ST-segment elevation, < 6 hours from the onset of chest pain and preceding symptoms of angina pectoris with primary percutaneous coronary intervention.
    Arm Title
    Group 3 - without angina pectoris + STEMi + RIC + PCI
    Arm Type
    Active Comparator
    Arm Description
    Patients with acute myocardial infarction with ST-segment elevation, < 6 hours from the onset of chest pain and without preceding symptoms of angina pectoris with primary percutaneous coronary intervention during which it's carried out remote ischemic conditioning (RIC)
    Arm Title
    Group 4 - without angina pectoris + STEMI + PCI
    Arm Type
    No Intervention
    Arm Description
    Patients with acute myocardial infarction with ST-segment elevation, < 6 hours from the onset of chest pain and without preceding symptoms of angina pectoris with primary percutaneous coronary intervention.
    Arm Title
    Group 5 - healthy + RIC
    Arm Type
    Active Comparator
    Arm Description
    healthy volunteers of the same age and sex, whose samples will be taken after the RIC procedure
    Intervention Type
    Device
    Intervention Name(s)
    Remote Ischemic Conditioning (RIC)
    Intervention Description
    RIC is a non-invasive method that achieves a state of intermittent hypoxia, and is performed by inflating the cuff of the pressure gauge on the left upper arm to 200 mmHg in 4 episodes of five-minute ischemia and reperfusion alternately for 45 minutes.
    Primary Outcome Measure Information:
    Title
    Measurement of the concentration and dynamics of troponin T (Trop T)
    Description
    Serum concentrations (ng/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Time Frame
    24 hour
    Title
    Measurement of the concentration and dynamics of cardiac myosin binding protein C (cMyBP-C)
    Description
    Serum concentrations (ng/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Time Frame
    24 hour
    Title
    Measurement of the concentration and dynamics of creatine kinase-MB (CK-MB)
    Description
    Serum concentrations (ng/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Time Frame
    24 hour
    Title
    Measurement of the concentration and dynamics of oxidation/mitochondrial parameter, hypoxia-induced factor 1 alpha (HIF 1α)
    Description
    serum concentrations (pg/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Time Frame
    24 hour
    Title
    Measurement of the concentration and dynamics of metabolic parameter, glycine
    Description
    Serum concentrations (μmol/l) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Time Frame
    24 hour
    Title
    Measurement of the concentration and dynamics of metabolic parameter, kynurenine
    Description
    Serum concentrations (μmol/l) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Time Frame
    24 hour
    Title
    Measurement of the concentration and dynamics of metabolic parameter, succinate
    Description
    Serum concentrations (μM) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Time Frame
    24 hour
    Title
    Measurement of the concentration and dynamics of immunological parameter, interleukin 1 beta (IL-1 beta)
    Description
    Serum concentrations (pg/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Time Frame
    24 hour
    Title
    Measurement of the concentration and dynamics of immunological parameter, transforming growth factor beta (TGF beta)
    Description
    Serum concentrations (ng/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Time Frame
    24 hour
    Title
    Measurement of the concentration and dynamics of immunological parameter, monocyte chemoattraction protein 1 (MCP-1)
    Description
    Serum concentrations (pg/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
    Time Frame
    24 hour
    Secondary Outcome Measure Information:
    Title
    The changes in serum values of immunometabolic parameters and creatine kinase-MB
    Description
    The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with a degree of tissue damage creatine kinase-MB.
    Time Frame
    24 hour
    Title
    The changes in serum values of immunometabolic parameters and troponin T
    Description
    The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with a degree of tissue damage troponin T
    Time Frame
    24 hour
    Title
    The changes in serum values of immunometabolic parameters and left heart ejection fraction
    Description
    The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with functional assessment of the heart muscle, ejection fraction (%).
    Time Frame
    7 day
    Title
    The changes in serum values of immunometabolic parameters in PCI groups and angina pectoris (AP) group
    Description
    The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with the data of patients diagnosed with angina pectoris (AP).
    Time Frame
    24 hour
    Title
    The changes in serum values of immunometabolic parameters in PCI groups and the group of healthy volunteers
    Description
    The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with the group of healthy volunteers in whom the RIC method was used.
    Time Frame
    24 hour

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: For group 1: Acute coronary syndrome; angina pectoris (chest pain with negative troponin T with or without changes in electrocardiographic findings); Monovascular disease, preocclusive stenosis with TIMI(thrombolysis in myocardial infarction) > 1 on the left main or anterior descending branch of the left coronary artery Visually estimated diameter of the epicardial coronary artery from 2.5 mm to 4.0 mm For group 2: Acute myocardial infarction with ST-segment elevation (ST-segment elevation> 0.1 mV in two or more leads, or> 0.2 mV in V1-V3) <6 hours from the onset of chest pain Symptoms of angina pectoris preceding acute myocardial infarction Monovascular disease, occlusion or preocclusive stenosis of the anterior descending branch of the left coronary artery with TIMI <1 flow in STEMI; After opening the artery and setting the stent TIMI> 2 flow Visually estimated epicardial coronary artery diameter up to 2.5 mm to 4.0 mm For groups 3 and 4: Acute myocardial infarction with ST-segment elevation (ST-segment elevation> 0.1 mV in two or more leads, or> 0.2 mV in V1-V3) <6 hours from the onset of chest pain No symptoms of angina pectoris preceding acute myocardial infarction Monovascular disease, occlusion or preocclusive stenosis of the anterior descending branch of the left coronary artery with TIMI <1 flow in STEMI; After opening the artery and stent placement TIMI> 2 flow Visually estimated diameter of the epicardial coronary artery from 2.5 mm to 4.0 mm For all groups: Age of patients over 18 years Signed written informed consent to be included in the survey Exclusion Criteria: Cardiac arrest before or after PCI; Cardiogenic shock; Previous myocardial infarction or revascularization of the heart; Anginal pain before the onset of STEMI in patients to be subjected to RIC; Patients with end-stage renal or hepatic disease, diabetics with developed micro and macrovascular complications, oncology patients; Significant collaterals in the area of the occluded artery (Rentrop gradus> 1); Previous use of nitrates and corticosteroids; Pregnant or breastfeeding women; Iodine allergy (contrast media); Increase in body temperature > 37.5 ° C Participation in another clinical trial Randomly selected (coin toss) patients will be randomized to group 3 and 4, respectively, for percutaneous coronary intervention with or without RIC
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Koraljka Benko, MD
    Phone
    +38598462387
    Email
    bkoraljka@yahoo.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Koraljka Benko, MD
    Organizational Affiliation
    CHC Rijeka; Croatia
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    23281415
    Citation
    Hausenloy DJ, Yellon DM. Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J Clin Invest. 2013 Jan;123(1):92-100. doi: 10.1172/JCI62874. Epub 2013 Jan 2.
    Results Reference
    background
    PubMed Identifier
    23270554
    Citation
    Hausenloy DJ. Cardioprotection techniques: preconditioning, postconditioning and remote conditioning (basic science). Curr Pharm Des. 2013;19(25):4544-63. doi: 10.2174/1381612811319250004.
    Results Reference
    background
    PubMed Identifier
    32509561
    Citation
    Han X, Jeong MH, Won J, Kim Y, Kim MC, Sim DS, Hong YJ, Kim JH, Ahn Y. Impact of Previous Angina on Clinical Outcomes in ST-Elevation Myocardial Infarction Underwent Percutaneous Coronary Intervention. Chonnam Med J. 2020 May;56(2):136-143. doi: 10.4068/cmj.2020.56.2.136. Epub 2020 May 25.
    Results Reference
    background
    PubMed Identifier
    25593060
    Citation
    Heusch G, Botker HE, Przyklenk K, Redington A, Yellon D. Remote ischemic conditioning. J Am Coll Cardiol. 2015 Jan 20;65(2):177-95. doi: 10.1016/j.jacc.2014.10.031.
    Results Reference
    background

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    Immunometabolic Pattern of Intermittent Hypoxia During ST-segment Elevation Myocardial Infarction

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