Coronary OcclusionPhase 1NCT00365326
Safety and Efficacy of Autologous, Intracoronary Stem Cell Injections in Total Coronary Artery Occlusions
A Phase 1 study testing Catheter-based intracoronary injection in people with Coronary Occlusion, run by Case Western Reserve University at 1 site in United States.
Trial summary
This phase I clinical trial will evaluate the safety and efficacy of intra-coronary injection of AC133 selected autologous marrow-derived stem cells in patients with chronic coronary artery occlusion. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Coronary Occlusion
- What is being tested?
- Catheter-based intracoronary injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2006to Jun 2008
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- The patient must have at least one region of chronically ischemic myocardium formerly perfused by a coronary artery which is now 100% occluded and not revascularizable by conventional percutaneous or surgical methods.
- Well-established collateral vessels at least 1.5-mm luminal diameter by coronary angiography to the chronically ischemic myocardium must be identified at the time of diagnostic coronary angiography.
- Evidence of viable myocardium in the area supplied by collateral conduits intended for stem cell infusion must be demonstrated by nuclear (sestamibi) stress imaging.
- Left ventricular ejection fraction of >45% as per 2D echocardiogram.
- Patient must experience class II - IV angina as defined by the Canadian Cardiovascular Society (CCS).
- Patient will be followed by the investigating team over the 12 month follow-up period.
- The patient must be at least 18 years of age and have signed an informed consent.
- If the patient is a female of child-bearing potential, a pregnancy test is negative.
Who cannot join
- Patients meeting any of the following exclusion criteria will be excluded from the study:
- Patient with coronary lesions amenable to percutaneous coronary intervention including brachytherapy, or where CABG is indicated.
- Any contraindication for cardiac catheterization and percutaneous coronary intervention as per institutional guidelines.
- Any contraindication for bone marrow aspiration as per institutional guidelines.
- Myocardial infarction within the previous 3 months.
- Documented bleeding diathesis.
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- Known malignancy involving the hematopoietic/lymphoid system.
- Patients with baseline ECG abnormalities that would hinder interpretation of baseline ECG uninterpretable for ischemia (e.g., left bundle branch block, left ventricular hypertrophy with strain pattern, Wolff-Parkinson-White syndrome).
- Patients with severe co-morbidities including renal failure (serum creatinine > 2.0).
- Anticipated unavailability for follow-up visits secondary to psychological or social reasons.
- NYHA class III or IV congestive heart failure
- Anemia with hemoglobin concentration < 8 mg/dl
- Thrombocytopenia with platelet count < 100 x 103
Trial locations and contacts
1 site in 1 country.
United States1 site
Case Western Reserve University
Cleveland, Ohio, 44106
About this study
This phase I clinical trial will evaluate the safety and efficacy of intra-coronary injection of AC133 selected autologous marrow-derived stem cells in patients with chronic coronary artery occlusion. A clinical study to determine the therapeutic potential of marrow-derived stem cells as an adjunct therapy to current standard therapies for CAD is warranted. The current initiative is to investigate a model of chronic myocardial ischemia and (1) to determine whether intra-coronary injection of selected autologous marrow-derived AC133 stem cells is reasonably safe for use in humans and (2) if this treatment shows any improvement in coronary perfusion, as assessed using non-invasive imaging. This study is structured to evaluate the feasibility and safety of autologous AC133+ bone marrow-derived stem cell via intra-coronary injection into documented ischemic but viable myocardial zones via established collateral vessels. The epicardial vessel that normally supplies the ischemic zone must be 100% chronically occluded and considered non-revascularizable by percutaneous means.
Read the detailed description
This study is composed of one phase. The objective of Phase I is to assess the safety and feasibility of performing escalating doses of autologous AC133+ selected bone marrow-derived stem cell with intracoronary infusion via epicardial vessels supplying collateral flow to areas of viable ischemic myocardium in the distribution of a chronic totally occluded vessel. Additionally, focus on the assessment of the benefit achieved from the infusion of stem cells and subsequent angiogenesis at 6 months will be observed.
Potential candidates are patients with a known total occlusion of an epicardial vessel, with a documented chronically ischemic territory supplied by collateral conduits.
Secondary Objectives include:
- Improvement in ETT as determined by: total exercise duration on the 6 month ETT in seconds time to: onset of angina, one mm ST depression, onset of angina or one mm ST depression (whichever occurs first)
- Reduction in the area of ischemia will be evaluated by nuclear (sestamibi) stress imaging with exercise or pharmacologic stress.
- Improvement in viability within the chronically ischemic zone as measured by nuclear (sestamibi) stress imaging.
- Improvement in angina as per Angina Questionnaire (The Seattle Angina Questionnaire) at 7, 14, 30, 90, 180, and 365 days.
- Major adverse cardiac events (MACE) assessment (composite endpoint including cardiac death, myocardial infarction, ischemia-driven target vessel revascularization, CABG, CVA, and rehospitalization for angina), MACE definitions: Myocardial Infarction (All ST segment elevation MIs as diagnosed on electrocardiogram by a staff cardiologist and all non-ST segment elevation MIs as defined by elevation in cardiac enzyme markers per the hospital laboratory guidelines) Cerebral Vascular Accidents (e.g., acute neurological event).
- Concomitant Medication usage (e.g., changes in utilization of PRN or sublingual nitroglycerin for angina)
- ECG changes at day of discharge, 7, 14, 30, 90, 180, and 365 days.
- Functional capacity (e.g., exercise duration (time) and changes in METS achieved on treadmill study at 6 month follow-up).
- Echocardiogram assessment of left ventricular ejection fraction and regional wall motion abnormalities at 180 days (e.g., changes in regional wall motion score and/or changes in left ventricular ejection fraction).
- Conditions
- Coronary Occlusion
- Being tested
- Catheter-based intracoronary injection
- Keywords
- AC133, coronary, bone marrow, autologous, coronary artery disease
- Medical subject headings
- Coronary Occlusion, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Catheter-based intracoronary injectionBiological
This Phase I single arm clinical study, was designed to assess the safety and feasibility of a dose escalating intracoronary infusion of autologous bone marrow (BM)-derived CD133+ stem cell therapy to the patients with chronic total occlusion (CTO) and ischemia. Nine patients were received CD133+ cells into epicardial vessels supplying collateral flow to areas of viable ischemic myocardium in the distribution of the CTO.
| Study group | Role | What they receive |
|---|---|---|
| Treatment with autologous bone marrow (BM)-derived CD133+ stem cell therapy | Experimental | The Phase I single arm clinical study, was designed to assess the safety and feasibility of a dose escalating intracoronary infusion of autologous bone marrow (BM)-derived CD133+ stem cell therapy to the patients with chronic total occlusion (CTO) and ischemia. Receives: Biological: Catheter-based intracoronary injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess the safety and feasibility of performing autologous AC133+ selected bone marrow-derived stem cell intra-coronary infusion and determine whether any benefit is achieved from the infusion of stem cells by non-invasive cardiac assessment.
Determine whether intra-coronary injection of selected autologous marrow-derived AC133 stem cells is reasonably safe for use in humans
Measured: 7days-6months
Secondary outcomes (1)
Improvement in ETT, reduction in ischemic area, viability improvement (nuclear stress imaging), improvement in angina (Seattle Angina Questionnaire), major adverse cardiac events assessment, echocardiogram assessment of left %EF and regional wall motion.
Determine if this treatment shows any improvement in coronary perfusion, as assessed using non-invasive imaging.
Measured: 7 days-6months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2006 (estimated)
- Study startJan 2006
- Primary completionJun 2007
- Study completionJun 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary OcclusionStudies of the same condition, open and under way.
- 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
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Western Reserve University
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospitals Cleveland Medical Center, Arteriocyte, Inc.
- Responsible party
- Sponsor
- Investigators
- Dale Adler, MD, Principal investigator, Case Western Reserve UniversityHillard Lazarus, MD, Principal investigator, Case Western Reserve University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00365326
- Sponsor's protocol ID
- HFM-705
- Status last verified
- Aug 2006
- First submitted
- 15 Aug 2006
- Last updated
- 24 Mar 2022
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Autologous, Intracoronary Stem Cell Injections in Total Coronary Artery Occlusions
- ClinicalTrials.gov ID
- NCT00365326
- Acronym / sponsor ID
- HFM-705
- Conditions
- Coronary Occlusion
- Keywords
- AC133, coronary, bone marrow, autologous, coronary artery disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Case Western Reserve UniversityUniversity, hospital or other
- Collaborators
- University Hospitals Cleveland Medical Center, Arteriocyte, Inc.
- Study start
- Jan 2006
- Primary completion
- Jun 2007 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 17 Aug 2006 (estimated)
- 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.
This phase I clinical trial will evaluate the safety and efficacy of intra-coronary injection of AC133 selected autologous marrow-derived stem cells in patients with chronic coronary artery occlusion. A clinical study to determine the therapeutic potential of marrow-derived stem cells as an adjunct therapy to current standard therapies for CAD is warranted. The current initiative is to investigate a model of chronic myocardial ischemia and (1) to determine whether intra-coronary injection of selected autologous marrow-derived AC133 stem cells is reasonably safe for use in humans and (2) if this treatment shows any improvement in coronary perfusion, as assessed using non-invasive imaging. This study is structured to evaluate the feasibility and safety of autologous AC133+ bone marrow-derived stem cell via intra-coronary injection into documented ischemic but viable myocardial zones via established collateral vessels. The epicardial vessel that normally supplies the ischemic zone must be 100% chronically occluded and considered non-revascularizable by percutaneous means.
Detailed description
This study is composed of one phase. The objective of Phase I is to assess the safety and feasibility of performing escalating doses of autologous AC133+ selected bone marrow-derived stem cell with intracoronary infusion via epicardial vessels supplying collateral flow to areas of viable ischemic myocardium in the distribution of a chronic totally occluded vessel. Additionally, focus on the assessment of the benefit achieved from the infusion of stem cells and subsequent angiogenesis at 6 months will be observed.
Potential candidates are patients with a known total occlusion of an epicardial vessel, with a documented chronically ischemic territory supplied by collateral conduits.
Secondary Objectives include:
- Improvement in ETT as determined by: total exercise duration on the 6 month ETT in seconds time to: onset of angina, one mm ST depression, onset of angina or one mm ST depression (whichever occurs first)
- Reduction in the area of ischemia will be evaluated by nuclear (sestamibi) stress imaging with exercise or pharmacologic stress.
- Improvement in viability within the chronically ischemic zone as measured by nuclear (sestamibi) stress imaging.
- Improvement in angina as per Angina Questionnaire (The Seattle Angina Questionnaire) at 7, 14, 30, 90, 180, and 365 days.
- Major adverse cardiac events (MACE) assessment (composite endpoint including cardiac death, myocardial infarction, ischemia-driven target vessel revascularization, CABG, CVA, and rehospitalization for angina), MACE definitions: Myocardial Infarction (All ST segment elevation MIs as diagnosed on electrocardiogram by a staff cardiologist and all non-ST segment elevation MIs as defined by elevation in cardiac enzyme markers per the hospital laboratory guidelines) Cerebral Vascular Accidents (e.g., acute neurological event).
- Concomitant Medication usage (e.g., changes in utilization of PRN or sublingual nitroglycerin for angina)
- ECG changes at day of discharge, 7, 14, 30, 90, 180, and 365 days.
- Functional capacity (e.g., exercise duration (time) and changes in METS achieved on treadmill study at 6 month follow-up).
- Echocardiogram assessment of left ventricular ejection fraction and regional wall motion abnormalities at 180 days (e.g., changes in regional wall motion score and/or changes in left ventricular ejection fraction).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment with autologous bone marrow (BM)-derived CD133+ stem cell therapy | Experimental | Biological: Catheter-based intracoronary injectionThe Phase I single arm clinical study, was designed to assess the safety and feasibility of a dose escalating intracoronary infusion of autologous bone marrow (BM)-derived CD133+ stem cell therapy to the patients with chronic total occlusion (CTO) and ischemia. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- The patient must have at least one region of chronically ischemic myocardium formerly perfused by a coronary artery which is now 100% occluded and not revascularizable by conventional percutaneous or surgical methods.
- Well-established collateral vessels at least 1.5-mm luminal diameter by coronary angiography to the chronically ischemic myocardium must be identified at the time of diagnostic coronary angiography.
- Evidence of viable myocardium in the area supplied by collateral conduits intended for stem cell infusion must be demonstrated by nuclear (sestamibi) stress imaging.
- Left ventricular ejection fraction of >45% as per 2D echocardiogram.
- Patient must experience class II - IV angina as defined by the Canadian Cardiovascular Society (CCS).
Key exclusion criteria (13 listed)
- Patient with coronary lesions amenable to percutaneous coronary intervention including brachytherapy, or where CABG is indicated.
- Any contraindication for cardiac catheterization and percutaneous coronary intervention as per institutional guidelines.
- Any contraindication for bone marrow aspiration as per institutional guidelines.
- Myocardial infarction within the previous 3 months.
- Documented bleeding diathesis.
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 |
|---|---|---|
| Catheter-based intracoronary injectionThis Phase I single arm clinical study, was designed to assess the safety and feasibility of a dose escalating intracoronary infusion of autologous bone marrow (BM)-derived CD133+ stem cell therapy to the patients with chronic total occlusion (CTO) and ischemia. Nine patients were received CD133+ cells into epicardial vessels supplying collateral flow to areas of viable ischemic myocardium in the distribution of the CTO. | Biological | Treatment with autologous bone marrow (BM)-derived CD133+ stem cell therapy |
Primary outcome
Assess the safety and feasibility of performing autologous AC133+ selected bone marrow-derived stem cell intra-coronary infusion and determine whether any benefit is achieved from the infusion of stem cells by non-invasive cardiac assessment.
Time frame: 7days-6months
Determine whether intra-coronary injection of selected autologous marrow-derived AC133 stem cells is reasonably safe for use in humans
1 secondary outcome
Improvement in ETT, reduction in ischemic area, viability improvement (nuclear stress imaging), improvement in angina (Seattle Angina Questionnaire), major adverse cardiac events assessment, echocardiogram assessment of left %EF and regional wall motion.
Time frame: 7 days-6months
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 24 Mar 2022.
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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.
Dale Adler, MD principal investigator
Case Western Reserve University
Hillard Lazarus, MD principal investigator
Case Western Reserve University
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 Catheter-based intracoronary injection in people with Coronary Occlusion, run by Case Western Reserve University 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 8 inclusion and 13 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 24 Mar 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?
Assess the safety and feasibility of performing autologous AC133+ selected bone marrow-derived stem cell intra-coronary infusion and determine whether any benefit is achieved from the infusion of stem cells by non-invasive cardiac assessment. (time frame: 7days-6months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Mar 2022.