Atherosclerosis, CoronaryPhase 1NCT03471611
Study of Intracoronary CD34+ Cell Administration in Patients With Early Coronary Atherosclerosis
A Phase 1 study testing Autologous CD34+ Cells and Granulocyte Colony-Stimulating Factor (G-CSF) in people with Atherosclerosis, Coronary, run by Mayo Clinic at 1 site in United States.
Trial summary
How safe and effective are CD34+ cell intracoronary injections for treating coronary endothelial dysfunction (CED)? Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Atherosclerosis, Coronary
- What is being tested?
- Autologous CD34+ Cells and Granulocyte Colony-Stimulating Factor (G-CSF)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jun 2018to 2 Oct 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
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
How safe and effective are CD34+ cell intracoronary injections for treating coronary endothelial dysfunction (CED)?
Read the 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.
- Conditions
- Atherosclerosis, Coronary
- Being tested
- Autologous CD34+ Cells, Granulocyte Colony-Stimulating Factor (G-CSF)
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous CD34+ CellsDrug
The dose will be 1x10^5 cells/kg, injected at the rate of 10 ml/min
Granulocyte Colony-Stimulating Factor (G-CSF)Drug
Also called Neupogen, Neulasta
5mg/kg twice daily
| Study group | Role | What they receive |
|---|---|---|
| Subjects with Endothelial Dysfunction | Experimental | 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. Receives: Drug: Autologous CD34+ Cells; Drug: Granulocyte Colony-Stimulating Factor (G-CSF) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects experiencing adverse events
Measured: 12 months
Number of subjects experiencing serious adverse events
Measured: 12 months
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2018
- Study start15 Jun 2018
- Primary completion2 Oct 2020
- Study completion2 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Atherosclerosis, CoronaryStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Amir Lerman, Mayo Clinic
- Investigators
- Amir Lerman, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03471611
- Sponsor's protocol ID
- 17-005743
- Status last verified
- Feb 2022
- First submitted
- 14 Mar 2018
- Last updated
- 7 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 34923853
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03471611
- Acronym / sponsor ID
- 17-005743
- Conditions
- Atherosclerosis, Coronary
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 15 Jun 2018 (actual)
- Primary completion
- 2 Oct 2020 (actual)
- Study completion
- 2 Oct 2020 (actual)
- First posted
- 20 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Subjects with Endothelial Dysfunction | Experimental | Drug: Autologous CD34+ Cells, Drug: Granulocyte Colony-Stimulating Factor (G-CSF)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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous CD34+ CellsThe dose will be 1x10^5 cells/kg, injected at the rate of 10 ml/min | Drug | Subjects with Endothelial Dysfunction |
| Granulocyte Colony-Stimulating Factor (G-CSF)Also: Neupogen, Neulasta5mg/kg twice daily | Drug | Subjects with Endothelial Dysfunction |
Primary outcome
Number of subjects experiencing adverse events
Time frame: 12 months
Number of subjects experiencing serious adverse events
Time frame: 12 months
Number of subjects experiencing Major Adverse Cardiovascular Events (MACE)
Time frame: 12 months
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2022.
- Derived from this study: PubMed 34923853Corban 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.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amir Lerman principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Autologous CD34+ Cells and Granulocyte Colony-Stimulating Factor (G-CSF) in people with Atherosclerosis, Coronary, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of subjects experiencing adverse events (time frame: 12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03471611, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2022.