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Study of Intracoronary CD34+ Cell Administration in Patients With Early Coronary Atherosclerosis

Primary Purpose

Atherosclerosis, Coronary

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Autologous CD34+ Cells

Granulocyte Colony-Stimulating Factor (G-CSF)

About this trial

This is an interventional treatment trial for Atherosclerosis, Coronary

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnosis of coronary endothelial dysfunction based on coronary angiogram and acetylcholine comprehensive coronary physiology study
Able to provide informed written consent and willing to participate in all required study follow-up assessments

Exclusion Criteria:

Acute coronary syndrome or continuous/ongoing chest pain - unremitting and unresponsive to nitroglycerin or rest - persisting 4 or more days before stent placement. If the chest pain syndrome is transient and/or intermittent - even if it began more than 3 days prior to admission - the patient is not excluded.
Subjects in cardiogenic shock (systolic pressure < 80mm/Hg, on vasopressors or intraaortic counter pulsation) at the time of consenting. Subjects who recover from cardiogenic shock by the time of consenting are eligible.
Subjects unable to receive antiplatelet agents (e.g. aspirin, clopidogrel, ticlopidine,prasugrel, etc).
Abnormal laboratory values (Hgb <11 mg/dL; glomerular filtration rate (GFR)<50; liver function tests (LFTs)>2x upper limit of normal).
Subjects receiving warfarin who have an international normalized ratio (INR) >2 at the end of the screening phase or with major bleeding requiring active transfusion support.
Subjects with severe cardiac valvular disease expected to undergo surgery within 1 year.
Subjects with known severe immunodeficiency states (AIDS).
Significant coronary artery disease on coronary angiogram
Cirrhosis requiring active medical management.
Malignancy requiring active treatment (except basal cell skin cancer).
Subjects with documented active alcohol and /or other substance abuse.
Females of child bearing potential unless a pregnancy test is negative within 7 days of the bone marrow harvest.
Re-occlusion of the infarct related artery (IRA) prior to the infusion procedure.
Planned revascularization intervention during the next 6 months. (A second PCI can be performed if done prior to qualifying cardiovascular magnetic resonance imaging (CMR) at least 96 hours post primary PCI).
Participation in an ongoing investigational trial.
Active or suspected bacterial infection requiring systemic intravenous antibiotics.
Additional factors deemed unsuitable for trial enrollment per discretion of principal investigator
Inmates

Sites / Locations

Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Subjects with Endothelial Dysfunction

Arm Description

Subjects will be treated with Granulocyte Colony-Stimulating Factor (G-CSF) for 5 days at a dose of 5 mg/kg twice daily. When count of CD34+ cells is sufficient, the CD34+ cells will be collected by apheresis. Autologous CD34+ cells will be injected into the subjects at a rate of 10 ml/min.

Outcomes

Primary Outcome Measures

Number of subjects experiencing adverse events

Number of subjects experiencing serious adverse events

Number of subjects experiencing Major Adverse Cardiovascular Events (MACE)

The most commonly reported major cardiovascular adverse events (MACE) include myocardial infarction, heart failure, percutaneous cardiac intervention, coronary artery bypass grafting, malignant dysrhythmia, cardiac shock, implantable cardiac defibrillator, malignant dysrhythmia and death.

Secondary Outcome Measures

Full Information

NCT ID

NCT03471611

First Posted

March 14, 2018

Last Updated

February 4, 2022

Sponsor

Mayo Clinic

1. Study Identification

Unique Protocol Identification Number

NCT03471611

Brief Title

Study of Intracoronary CD34+ Cell Administration in Patients With Early Coronary Atherosclerosis

Official Title

A Phase 1, Feasibility Study Testing the Safety and Feasibility of Intracoronary CD34+ Cell Administration on Coronary Endothelial Function in Patients With Early Coronary Atherosclerosis

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Completed

Study Start Date

June 15, 2018 (Actual)

Primary Completion Date

October 2, 2020 (Actual)

Study Completion Date

October 2, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mayo Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

How safe and effective are CD34+ cell intracoronary injections for treating coronary endothelial dysfunction (CED)?

Detailed Description

This is an open label, phase I study to determine safety and efficacy of CD34+ cells in the treatment and management of CED and early atherosclerosis. Coronary endothelial function will be assessed in all patients by the administration of intracoronary acetylcholine. Patients with endothelial dysfunction who meet study inclusion criteria will receive granulocyte cell stimulating factor (G-CSF), followed by apheresis. The mobilized peripheral cell product will be processed for selection of CD34+ stem cells, and the purified CD34+ cells will be administered intracoronary during cardiac catheterization. The patients will undergo repeat endothelial function assessment 6 months post-procedure, as well as clinical assessments as described below either via in-person assessment by a nurse or physician, or via phone-call using a standardized questionnaire at 1, 3, and 6 month follow-up visits. At one month, the patient will undergo basic laboratory testing including troponin levels, complete blood count (CBC), electrolyte panel, liver function testing and ECG. At 3 months, the patients will receive a phone follow-up by the study coordinator who will assess the patient for any clinical deterioration or significant worsening in symptoms. At 6 months, the patients will return for a clinical visit, which will include physical examination, basic laboratory testing and follow-up acetylcholine study with angiography to assess for change in endothelial function. The first three patients will be sequentially enrolled, and subsequent enrollment will be held until one month follow-up. Provided there are no safety concerns at this time, enrollment will continue.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Atherosclerosis, Coronary

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Subjects with Endothelial Dysfunction

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Autologous CD34+ Cells

Intervention Description

The dose will be 1x10^5 cells/kg, injected at the rate of 10 ml/min

Intervention Type

Drug

Intervention Name(s)

Granulocyte Colony-Stimulating Factor (G-CSF)

Other Intervention Name(s)

Neupogen, Neulasta

Intervention Description

5mg/kg twice daily

Primary Outcome Measure Information:

Title

Number of subjects experiencing adverse events

Time Frame

12 months

Title

Number of subjects experiencing serious adverse events

Time Frame

12 months

Title

Number of subjects experiencing Major Adverse Cardiovascular Events (MACE)

Description

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnosis of coronary endothelial dysfunction based on coronary angiogram and acetylcholine comprehensive coronary physiology study Able to provide informed written consent and willing to participate in all required study follow-up assessments Exclusion Criteria: Acute coronary syndrome or continuous/ongoing chest pain - unremitting and unresponsive to nitroglycerin or rest - persisting 4 or more days before stent placement. If the chest pain syndrome is transient and/or intermittent - even if it began more than 3 days prior to admission - the patient is not excluded. Subjects in cardiogenic shock (systolic pressure < 80mm/Hg, on vasopressors or intraaortic counter pulsation) at the time of consenting. Subjects who recover from cardiogenic shock by the time of consenting are eligible. Subjects unable to receive antiplatelet agents (e.g. aspirin, clopidogrel, ticlopidine,prasugrel, etc). Abnormal laboratory values (Hgb <11 mg/dL; glomerular filtration rate (GFR)<50; liver function tests (LFTs)>2x upper limit of normal). Subjects receiving warfarin who have an international normalized ratio (INR) >2 at the end of the screening phase or with major bleeding requiring active transfusion support. Subjects with severe cardiac valvular disease expected to undergo surgery within 1 year. Subjects with known severe immunodeficiency states (AIDS). Significant coronary artery disease on coronary angiogram Cirrhosis requiring active medical management. Malignancy requiring active treatment (except basal cell skin cancer). Subjects with documented active alcohol and /or other substance abuse. Females of child bearing potential unless a pregnancy test is negative within 7 days of the bone marrow harvest. Re-occlusion of the infarct related artery (IRA) prior to the infusion procedure. Planned revascularization intervention during the next 6 months. (A second PCI can be performed if done prior to qualifying cardiovascular magnetic resonance imaging (CMR) at least 96 hours post primary PCI). Participation in an ongoing investigational trial. Active or suspected bacterial infection requiring systemic intravenous antibiotics. Additional factors deemed unsuitable for trial enrollment per discretion of principal investigator Inmates

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Amir Lerman

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic in Rochester

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

34923853

Citation

Corban MT, Toya T, Albers D, Sebaali F, Lewis BR, Bois J, Gulati R, Prasad A, Best PJM, Bell MR, Rihal CS, Prasad M, Ahmad A, Lerman LO, Solseth ML, Winters JL, Dietz AB, Lerman A. IMPROvE-CED Trial: Intracoronary Autologous CD34+ Cell Therapy for Treatment of Coronary Endothelial Dysfunction in Patients With Angina and Nonobstructive Coronary Arteries. Circ Res. 2022 Feb 4;130(3):326-338. doi: 10.1161/CIRCRESAHA.121.319644. Epub 2021 Dec 20.

Results Reference

derived

Links:

URL

https://www.mayo.edu/research/clinical-trials

Description

Mayo Clinic Clinical Trials

Learn more about this trial

Study of Intracoronary CD34+ Cell Administration in Patients With Early Coronary Atherosclerosis

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