Phase II Combination Stem Cell Therapy for the Treatment of Severe Coronary Ischemia(CI)

• ClinicalTrials.gov Identifier: NCT00790764
• Recruitment Status: Suspended
• First Posted: November 13, 2008
• Last Update Posted: May 9, 2014
• Sponsor: TCA Cellular Therapy
• Information provided by (Responsible Party): TCA Cellular Therapy

Tracking Information

• First Submitted Date: November 12, 2008
• First Posted Date: November 13, 2008
• Last Update Posted Date: May 9, 2014
• Study Start Date: November 2008
• Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 12, 2008): Safety as measured by laboratory assessments, ecg and temperature. [ Time Frame: 2 weeks ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: November 12, 2008): Efficacy as measured by SPECT scan, MUGA scan and 2D Echogradiogram [ Time Frame: 6 months ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase II Combination Stem Cell Therapy for the Treatment of Severe Coronary Ischemia(CI)
• Official Title: Phase II Study for the Transfer of Bone Marrow-Derived Mononuclear and Mesenchymal StemCells Into the Myocardium for the Treatment of Severe Coronary Ischemia

Brief Summary

The present investigation will be a Phase II, single center, placebo-controlled, randomized, dose escalation, infusion modality (intracoronary vs transendocardial injection using the Cordis Biosense NOGASTAR TM Mapping Catheter with the Biosense MYOSTAR TM left ventricular injection catheter) transplantation of an autologous (your own stem cells) combination of bone marrow-derived stem cells into myocardium for the treatment of severe coronary ischemia.

The purpose of this research study is to determine if the infusion of a combination of stem cells obtained from the bone marrow of the same patient will contribute to the formation of new blood vessels in patients with symptomatic severe coronary ischemia(CI).

In this trial we will determine whether the combination stem cell treatment is safe, feasible and results in the development of mature stable and/or collateral vessels and improvement of cardiac function.

Coronary Ischemia (CI) is intractable angina due to severe coronary artery disease which can seriously decrease blood flow to the heart.

CI needs a comprehensive treatment since the condition will not improve on its own. The overall goal of the treatment is to increase blood flow to the heart and improve symptoms of angina.

The study hypothesis is based on the concept that the process of formation of new blood vessels is complex and requires the participation of several types of stem cells and growth factors. The lack of any of these components will produce vessels which are immature and unable to provide appropriate blood supply to the heart.

Patients eligible to participate in this study are those suffering from severe blockages of the vessels of the heart and are not candidates for percutaneous revascularization or surgical procedures.

Detailed Description

Enrolled individuals (60) will be divided in 2 Treatment groups for the infusion of the cell /placebo product:

1. Treatment Group A (30 individuals, including patients and placebo controls) will receive the product by intracoronary infusion,

2. Treatment Group B (30 individuals, including patients and placebo controls) will receive the product by transendocardial injections.

   In turn, each Treatment Group will consist of 2 subgroups of individuals that will receive the infusion of one of the two doses established of the cell product:

3. In treatment SubGroup 1, 10 individuals will receive the "low dose" of the cell product and 5 individuals will receive the placebo product.
4. In treatment SubGroup 2, 10 individuals will receive the "high dose" of the cell product and 5 individuals will receive the placebo product

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Heart Disease
• Blocked Arteries
• Coronary Ischemia
• Coronary Disease
• Coronary Artery Disease
• Coronary Atherosclerosis

Intervention

• Biological: MESENDO
  For the cell product, proper aliquots of each cell type will be taken to fulfill the doses established for this protocol. The two aliquots will be mixed and resuspended to a final volume of 3 ml in the 'Final Suspension Medium' which consists of Dulbecco's Phosphate Buffered Saline (DPBS), containing 5% human serum albumin.
• Other: placebo
  For placebo, 3 ml of the 'Final Suspension Medium' which consists of Dulbecco's Phosphate Buffered Saline (DPBS), containing 5% human serum albumin will be transferred to a 5 ml syringe

Study Arms

• Placebo Comparator: Placebo
  20 individuals will receive placebo.
  Intervention: Other: placebo
• Experimental: MESENDO
  Active combination autologous stem cell therapy. 40 individuals will receive MESENDO in either the "high" or "low" dose treatment groups.
  Intervention: Biological: MESENDO

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Suspended
• Estimated Enrollment (submitted: November 12, 2008): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2014
• Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age 18 to 80
• Male or female
• Angina pectoris: Canadian Cardiovascular Society Class III or IV or symptoms consistent with angina equivalent (dyspnea) CCS Class III or IV (Functional Class)
• Chronic coronary artery disease in at least one epicardial vessel with stenosis > 70% by coronary angiography within the last 6 months
• Stable medical therapy for at least one month
• Reversible perfusion defects by SPECT
• Not a candidate for coronary artery by-pass surgery due to poor targets or small vessels and not a candidate for percutaneous intervention due to small vessels or unreachable coronary lesions due to complicated anatomy

Exclusion Criteria:

• Inability to give written informed consent
• Previous angiogenic therapy or myocardial laser therapy
• Recent (< 4 weeks) acute ST-elevation myocardial infarction
• Patients with severe valvular heart disease
• Recent malignancy or radiation therapy (< 6 months) and not expected to survive 6 months
• Known sensitivity to gentamycin and/or amphotericin B
• Use or expected use of antineoplastic drugs
• Renal insufficiency with creatinine greater than 2.7 unless on dialysis
• WBC greater than 13,000 or lower than 3,000
• Hematocrit lower than 30 or higher than 50
• Platelet counts lower than 60,000 or higher than 500,000
• Child bearing potential without use of contraceptives
• Pregnant or planning to become pregnant
• Any illness which, in the investigator's judgment, will interfere with the patient's ability to comply with the protocol, compromise patient's safety, or interfere with the interpretation of the sturdy results
• Any illness which might affect patient's survival over the study follow-up period
• History of skeletal muscle disease, either primary (i.e. myopathy) or secondary (i.e. ischemic) or any underlying myopathy such as myasthenia gravis, muscular dystrophy, etc
• Patients with active infectious disease and/or who are known to have tested positive for HIV, HTLV, HBV-sAg, HCV, AST or ALT > 2 times ULRR
• Cardiogenic shock
• Any significant laboratory abnormality which will in the investigator's opinion interfere with the patient's ability to comply with the protocol, compromise the patient's safety, or interfere with the interpretation of the study result

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00790764
• Other Study ID Numbers: 2008--03-II
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: TCA Cellular Therapy
• Study Sponsor: TCA Cellular Therapy
• Collaborators: Not Provided

Investigators

• Principal Investigator: Gabriel P. Lasala, MD; TCA Cellular Therapy

• PRS Account: TCA Cellular Therapy
• Verification Date: April 2011