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Heart DiseasePhase 1NCT01557543

Stem Cell Injection to Treat Heart Damage During Open Heart Surgery

A Phase 1 study testing Cell Therapy in people with Heart Disease and Ischemic Heart Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Background: Bone marrow stromal stem cells (also known as mesenchymal stem cells) have been isolated and are found to make large amounts of growth factors. Because they make growth factors, these cells can help re-grow tissue and encourage repair of damaged tissue. Read more about this study

Who is it for?
Ages 18 to 85 years
What is being tested?
Cell Therapy
Type of treatment
Injection or infusion
How many people
24 participants
Where
2 sitesUnited States
Study dates
29 Feb 2012to 18 Jun 2018
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 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Consenting adult patients (male or female, aged above 18 and less than or equal to 85), and
  • Plans to undergo CABG or TMR at the NIH Heart Center at Suburban Hospital and are willing to participate.
  • Must meet indications for CABG or TMR:
  • Indications for CABG (31)
  • Significant left main coronary artery stenosis (> 50% reduction in lumen diameter).
  • Left main equivalent: significant (greater than or equal to70%) stenosis of proximal LAD and proximal left circumflex artery.
Show all 42Show fewer
  • Three-vessel disease (stenosis of 50% or more in all 3 major coronary territories). (Survival benefit is greater when LVEF is
  • <0.50.)
  • Two-vessel disease with significant proximal LAD stenosis and either EF <0.50 or demonstrable ischemia on noninvasive
  • testing.
  • One- or 2-vessel coronary artery disease without significant proximal LAD stenosis, but with a large area of viable
  • myocardium and high-risk criteria on noninvasive testing.
  • Indications for TMR (32, 33).
  • Canadian Cardiovascular Class III or IV angina that is refractory to maximal medical therapy.
  • Reversible ischemia of the left ventricular free wall and coronary artery disease corresponding to the regions of myocardial
  • ischemia.
  • In all regions of the myocardium, the coronary disease must not be amenable to coronary artery bypass graft (CABG) or
  • percutaneous transluminal coronary angioplasty (PTCA), due to:
  • severe diffuse disease,
  • lack of suitable targets for complete revascularization,
  • lack of suitable conduits for complete revascularization
  • Stable Angina. Patient?s clinical state has to be stable to receive surgical treatment. Patients must have received or currently receiving standard of care medical therapy(33) for at least 4 weeks prior to enrollment, to include:
  • Aspirin in the absence of contraindications in patients with prior MI
  • Beta-blockers as initial therapy in the absence of contraindications in patients with prior MI.
  • Lipid-lowering therapy in patients with documented CAD and LDL cholesterol greater than 130 mg/dL, with a target LDL of less
  • than 100 mg/dL
  • ACE inhibitor in patients with CAD (considered significant by angiography or previous MI) who also have diabetes and/or left
  • ventricular systolic dysfunction.
  • Three-vessel CAD. Multi-vessel diffuse coronary artery disease not amenable to percutaneous coronary intervention.
  • LV EF less than or equal to 50% by by MRI or Echocardiogram. The left ventricle ejection fraction less than 50% evidenced the diagnosis of heart failure indicating global weakness of myocardial contractility and leaves space for functional improvement.
  • Evidence of hypokinetic segment. Regional wall motion abnormality which includes regional low/no motion, or motion in opposite direction, is a good indication for invasive intervention and can be well-compared before and after treatment.
  • Laboratory tests showed no evidence of major organ dysfunction, bleeding disorder, or infectious diseases. Patients must have organ and marrow function as defined below:
  • Leukocytes greater than or equal to 2,500/mcL
  • Lymphocytes greater than or equal to 800/mcL
  • Platelets greater than or equal to 100,000/mcL
  • Total Bilirubin less than or equal to 2mg/dL
  • AST (SGOT)/ALT (SGPT) less than or equal 1.5 times
  • institutional upper limit of normal (ULN)
  • Creatinine less than or equal to institutional upper limit of
  • normal (ULN)
  • Must be willing to participate in 10-CC-0053 to obtain autologous bone marrow.
  • Patients must understand and sign an informed consent document that explains the nature of his/her cardiac disease, the procedures to be followed, the experimental nature of the treatment, alternative treatments, and potential risks and toxicities.

Who cannot join

  • Patients who have the following conditions will be excluded from the study:
  • Acute MI. Less than three months after recent acute myocardial infarction.
  • Unstable angina. Excluded due to the propensity to deteriorate into AMI.
  • Bleeding disorder, including history of familial hemophilia, signs and symptoms of easy bruising, petechiae, or platelet count < 80,000 cells/mcL. This disorder may unnecessarily complicate the operative procedure and postoperative recovery.
  • Severe respiratory disorder, including acute asthma, chronic bronchitis, severe chronic obstructive lung disease. A disorder that would complicate the operative procedure and postoperative recovery.
  • Unable to provide informed consent on this study or on 10-CC-0053.
Show all 10Show fewer
  • Unable to wait 3 weeks for surgery, which is the waiting period for ex-vivo cell expansion.
  • Reactive for anti-HIV, Hepatitis B surface antigen, anti-HCV or nucleic acid testing for HIV, Hepatitis B and C. An investigational component accompanying this major surgical procedure in the presence of infection has the potential to increase risk of complications, and manufacturing contaminated products risks contaminating other cellular products in CPS.
  • Pregnant or lactating females, due to the highly investigational nature of this study and its unknown effects on a developing fetus.
  • Allergic to Gentamicin.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Suburban Hospital

    Bethesda, Maryland, 20814

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Preliminary Assessment of Direct Intra-Myocardial Injection of Autologous Bone Marrow-derived Stromal Cells on Patients Undergoing Revascularization for CAD With Depressed Left Ventricular Function

Background:

  • Bone marrow stromal stem cells (also known as mesenchymal stem cells) have been isolated and are found to make large amounts of growth factors. Because they make growth factors, these cells can help re-grow tissue and encourage repair of damaged tissue. Tests on damaged heart muscle suggest that injecting these cells directly into damaged heart muscle can improve heart function. Researchers want to give stem cells to people who are having open heart surgery to see if they can help to repair heart muscle damage.
Read more

Objectives:

  • To test the safety and effectiveness of bone marrow stromal stem cell injections given during heart surgery to treat heart muscle damage.

Eligibility:

  • Individuals at least 18 years of age who are scheduled to have open heart surgery for heart artery or vein blockages.

Design:

  • Participants will be screened with a physical exam and medical history. Blood and urine samples will also be collected.
  • Participants will have bone marrow taken from both hip bones about 3 weeks before the heart surgery.
  • During the surgery, the stromal stem cells collected from the bone marrow will be given into the damaged portion of the heart muscle. The rest of the heart surgery will be performed according to standard procedures.
  • After the surgery, participants will be monitored for complications from the stromal stem cells.
  • Participants will have heart function tests to see if the stromal stem cell treatments were effective....
Read the detailed description

Background:

Many investigators now believe that bone marrow-derived stem cells or endothelial progenitor cells can be recruited to and incorporated into tissues undergoing neovascularization, including cardiac tissue.

Stem cells which include hematopoietic stem cells (HSCs), endothelial progenitor cells (EPCs), mesenchymal stem cells / stromal stem cells (MSCs), myoblasts, and undifferentiated side population cells have been used as an alternative therapeutic strategy for ischemic cardiovascular diseases that cannot be treated by routine interventional approaches.

In a porcine pre-clinical study we found that cells survived after intramyocardial injection and differentiated into vascular cells, smooth muscle or endothelial cells. Functional analysis of regional wall motion and ejection fraction demonstrated statistically significant improvement in function in cell treated animals after six weeks compared with baseline and sham controls.

A variety of studies have been conducted in subjects with coronary artery disease using different cell types and routes of administration. This study will be the first of its kind to administer autologous BMSC via direct intramyocardial injection in a rigorous clinical trial in the U.S.

Objectives:

To evaluate the safety and feasibility of direct intra-myocardial injection of autologous bone marrow stromal cells (BMSCs) in adult subjects undergoing coronary artery bypass graft (CABG) or transmyocardial revascularization (TMR).

A secondary objective is to assess whether direct intra-myocardial injection of autologous bone marrow stromal cells (BMSCs) improves the patient s cardiac function, quality of life, and reduces cardiac events compared with historical controls at three and six months after intervention.

Eligibility:

Adult subjects with three-vessel coronary artery disease who plan to undergo CABG or TMR at the NIH Heart Center at Suburban Hospital and are willing to participate, who have stable angina, LV EF less than or equal to 50%, and who have evidence of hypokinetic segments.

Subjects will be excluded if they have had a recent myocardial infarction (MI), bleeding disorder, infection, HIV or who are unable to wait 3 weeks for surgery while cells are being expanded prior to injection.

Design:

Bone marrow aspiration will be performed on subjects who suffer from ischemic heart disease with depressed left ventricular function three weeks before their admission to have CABG or TMR in the NIH Clinical Center Outpatient Clinic.

Data will be presented based on the subject s treatment regimen:

Group 1 CABG+Cells (total of 10 evaluable subjects)

Group 2 TMR + Cells (total of 10 evaluable subjects)

The autologous MSCs will be isolated from the marrow aspirate, cultured and expanded in vitro for 3 passages (approximately 21 days (+/- 4 days)) in the Clinical Center Cell Processing Laboratory (CPS), located in the Department of Transfusion Medicine (DTM), Clinical Center, NIH.

During the surgery at Suburban Hospital, the MSCs will be injected directly into the ischemic area after CABG or TMR. Patients will be assessed for functional improvements pre, 3, 6, 12 and 60 months after the surgery by transthoracic echocardiography and/or by MRI at pre, 3 and 6 months after surgery. Toxicity data will be reported from time of surgery to 6 months after surgery, unless later toxicities occur that are related to cell injection.

Being tested
Cell Therapy
Keywords
Coronary Artery Bypass Grafting, Coronary Artery Disease, Transmyocardial Revascularization, Bone Marrow Stromal Cells
Medical subject headings
Heart Diseases, Myocardial Ischemia, Coronary Artery Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cell TherapyOther

    Intramyocardial Injection of BMSCs

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To evaluate the safety and feasibility of direct intra-myocardial injection of autologous bone marrow stromal cells (BMSCs) in adult subjects undergoing coronary artery bypass graft (CABG) or transmyocardial revascularization (TMR).

Secondary outcomes (1)

  1. To assess if direct intra-myocardial injection of autologous BMSCs improves the patient's cardiac function, quality of life, and reduces cardiac events compared to historical controls at three and six months after intervention.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Mar 2012 (estimated)
  2. Study start29 Feb 2012
  3. Primary completion25 Jul 2017
  4. Study completion18 Jun 2018

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01557543
Sponsor's protocol ID
120078
Other IDs
12-H-0078
Status last verified
18 Jun 2018
First submitted
16 Mar 2012
Last updated
5 Jul 2018
Results posted
No

Publications

  • Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopoulos GD. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell. 1996 Dec 27;87(7):1171-80. doi: 10.1016/s0092-8674(00)81813-9.

    PubMed 8980224

  • Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N, Grunwald F, Aicher A, Urbich C, Martin H, Hoelzer D, Dimmeler S, Zeiher AM. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation. 2002 Dec 10;106(24):3009-17. doi: 10.1161/01.cir.0000043246.74879.cd.

    PubMed 12473544

  • Britten MB, Abolmaali ND, Assmus B, Lehmann R, Honold J, Schmitt J, Vogl TJ, Martin H, Schachinger V, Dimmeler S, Zeiher AM. Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast-enhanced magnetic resonance imaging. Circulation. 2003 Nov 4;108(18):2212-8. doi: 10.1161/01.CIR.0000095788.78169.AF. Epub 2003 Oct 13.

    PubMed 14557356

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cell Therapy in people with Heart Disease and Ischemic Heart Disease, run by National Heart, Lung, and Blood Institute (NHLBI) at 2 sites 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 42 inclusion and 10 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: stopped early, as of the sponsor's last update on 5 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 was stopped early. Results are not available in the source record.

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?

To evaluate the safety and feasibility of direct intra-myocardial injection of autologous bone marrow stromal cells (BMSCs) in adult subjects undergoing coronary artery bypass graft (CABG) or transmyocardial revascularization (TMR).. 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 NCT01557543, which also lists 3 linked publications.

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 5 Jul 2018.

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