The Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis Pilot Study (The POSEIDON-Pilot Study)

A Phase I/II, Randomized Pilot Study of the Comparative Safety and Efficacy of Transendocardial Injection of Autologous Mesenchymal Stem Cells Versus Allogeneic Mesenchymal Stem Cells in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01087996

Enrollment

Registered

2010-03-16

Start date

2010-03-31

Completion date

2012-10-31

Last updated

2015-05-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Stem Cell Transplantation

Keywords

Chronic Ischemic Left Ventricular

Brief summary

The technique of transplanting progenitor cells into a region of damaged myocardium, termed cellular cardiomyoplasty, is a potentially new therapeutic modality designed to replace or repair necrotic, scarred, or dysfunctional myocardium. Ideally, graft cells should be readily available, easy to culture to ensure adequate quantities for transplantation, and able to survive in host myocardium; often a hostile environment of limited blood supply and immunorejection. Whether effective cellular regenerative strategies require that administered cells differentiate into adult cardiomyocytes and couple electromechanically with the surrounding myocardium is increasingly controversial, and recent evidence suggests that this may not be required for effective cardiac repair. Most importantly, transplantation of graft cells should improve cardiac function and prevent adverse ventricular remodeling. To date, a number of candidate cells have been transplanted in experimental models, including fetal and neonatal cardiomyocytes, embryonic stem cell-derived myocytes, tissue engineered contractile grafts, skeletal myoblasts, several cell types derived from adult bone marrow, and cardiac precursors residing within the heart itself. There has been substantial clinical development in the use of whole bone marrow and skeletal myoblast preparations in studies enrolling both post-infarction patients, and patients with chronic ischemic left ventricular dysfunction and heart failure. The effects of bone-marrow derived mesenchymal stem cells (MSCs) have also been studied clinically. Currently, bone marrow or bone marrow-derived cells represent highly promising modality for cardiac repair. The totality of evidence from trials investigating autologous whole bone marrow infusions into patients following myocardial infarction supports the safety of this approach. In terms of efficacy, increases in ejection fraction are reported in the majority of the trials. Chronic ischemic left ventricular dysfunction resulting from heart disease is a common and problematic condition; definitive therapy in the form of heart transplantation is available to only a tiny minority of eligible patients. Cellular cardiomyoplasty for chronic heart failure has been studied less than for acute MI, but represents a potentially important alternative for this disease.

Interventions

BIOLOGICALAuto-hMSCs

Biological: Autologous human mesenchymal stem cells (Auto-hMSCs) Participants will receive 40 million cells/mL delivered in either a dose of 0.5 mL per injection x 1 injection for a total of 0.2 x 10\^8 (20 million) Auto-hMSCs, a dose of 0.5 mL per injection x 5 injections for a total of 1 x 10\^8 (100 million) Auto-hMSCs, or a dose of 0.5 mL per injection x 10 injections for a total of 2 x 10\^8 (200 million) Auto-hMSCs. The injections will be administered transendocardially during cardiac catheterization using the Biocardia Helical Infusion Catheter.

BIOLOGICALAllo-hMSCs

Biological: Allogeneic human mesenchymal stem cells (Allo-hMSCs) Participants will receive 40 million cells/mL delivered in either a dose of 0.5 mL per injection x 1 injection for a total of 0.2 x 10\^8 (20 million) Allo-hMSCs, a dose of 0.5 mL per injection x 5 injections for a total of 1 x 10\^8 (100 million) Allo-hMSCs, or a dose of 0.5 mL per injection x 10 injections for a total of 2 x 10\^8 (200 million) Allo-hMSCs. The injections will be administered transendocardially during cardiac catheterization using the Biocardia Helical Infusion Catheter.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

21 Years to 90 Years

Healthy volunteers

Inclusion criteria

* Diagnosis of chronic ischemic left ventricular dysfunction secondary to MI. * Be a candidate for cardiac catheterization. * Been treated with appropriate maximal medical therapy for heart failure or post-infarction left ventricular dysfunction. * Ejection fraction between 20% and 50%. * Able to perform a metabolic stress test.

Exclusion criteria

* Baseline glomerular filtration rate \<50 ml/min/1.73m2. * Presence of a mechanical aortic valve or heart constrictive device. * Documented presence of aortic stenosis (aortic stenosis graded as ≥+2 equivalent to an orifice area of 1.5cm2 or less). * Documented presence of moderate to severe aortic insufficiency (echocardio- graphic assessment of aortic insufficiency graded as ≥+2). * Evidence of a life-threatening arrhythmia (nonsustained ventricular tachycardia ≥20 consecutive beats or complete heart block) or QTc interval \>550 ms on screening ECG. In addition; patients with sustained or a short run of ventricular tachycardia on ECG or 48 hour Ambulatory ECG during the screening period will be removed from the protocol. * Documented unstable angina. * AICD firing in the past 60 days prior to the procedure. * Be eligible for or require coronary artery revascularization. * Have a hematologic abnormality as evidenced by hematocrit \< 25%, white blood cell \< 2,500/ul or platelet values \< 100,000/ul without another explanation. * Have liver dysfunction, as evidenced by enzymes (ALT and AST) greater than three times the ULN. * Have a coagulopathy condition = (INR \> 1.3) not due to a reversible cause. * Known, serious radiographic contrast allergy. * Known allergies to penicillin or streptomycin. * Organ transplant recipient. * Clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease free for 5 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma. * Non-cardiac condition that limits lifespan to \< 1 year. * On chronic therapy with immunosuppressant medication. * Serum positive for HIV, hepatitis BsAg, or hepatitis C. * Female patient who is pregnant, nursing, or of child-bearing potential and not using effective birth control.

Design outcomes

Primary

Measure	Time frame
Incidence of TE-SAE Define as Composite of Death, Non-fatal MI, Stroke, Hospitalization for Worsening Heart Failure, Cardiac Perforation, Pericardial Tamponade, Ventricular Arrhythmias >15 Sec. or With Hemodynamic Compromise or Atrial Fibrillation	One month post-catheterization

Secondary

Measure	Time frame	Description
CT Measure of Left Ventricular Ejection Fraction	Baseline Month 13 post-catheterization	—
CT Measure of End Diastolic Volume	Baseline Month 13 post-catheterization	—
CT Measure of End Systolic Volume	Baseline Month 13 post-catheterization	—
CT Infarct Size From Early Enhanced Defect: - Difference Between the Baseline and 13-month	Baseline Month 13 post-catheterization	Percentage change from 13-months post-catheterization to baseline.
Change in Distance Walked in 6-minutes From Baseline.	12-months	—
Change in Minnesota Living With Heart Failure Total Score	12 months	The Minnesota living with heart failure questionnaire uses a 6-point, zero to five, Likert scale. The total score is the sum of the 21 responses. The total score is considered the best measure of how heart failure and treatments impact a patients quality of life. The max score is 105, minimum score is 0. A lower score is considered a better quality of life.
Change in New York Heart Association Class at 12-months	12 months	—
CT Measure of Scar Size as % of LV Mass	Baseline Month 13 post-catheterization	—

Countries

United States

Participant flow

Recruitment details

Participants were enrolled between April 2, 2010 and September 14, 2011

Pre-assignment details

One patient did not receive Autologous MSCs because they became ineligible.

Participants by arm

Arm	Count
Allo-hMSCs Participants will receive an injection of 20 million, 100 million or 200 million allogeneic human mesenchymal stem cells. Allo-hMSCs : Biological: Allogeneic human mesenchymal stem cells (Allo-hMSCs) Participants will receive 40 million cells/mL delivered in either a dose of 0.5 mL per injection x 1 injection for a total of 0.2 x 10\^8 (20 million) Allo-hMSCs, a dose of 0.5 mL per injection x 5 injections for a total of 1 x 10\^8 (100 million) Allo-hMSCs, or a dose of 0.5 mL per injection x 10 injections for a total of 2 x 10\^8 (200 million) Allo-hMSCs. The injections will be administered transendocardially during cardiac catheterization using the Biocardia Helical Infusion Catheter.	15
Auto-hMSCs Participants will receive an injection of 20 million, 100 million or 200 million autologous human mesenchymal stem cells. Auto-hMSCs : Biological: Autologous human mesenchymal stem cells (Auto-hMSCs) Participants will receive 40 million cells/mL delivered in either a dose of 0.5 mL per injection x 1 injection for a total of 0.2 x 10\^8 (20 million) Auto-hMSCs, a dose of 0.5 mL per injection x 5 injections for a total of 1 x 10\^8 (100 million) Auto-hMSCs, or a dose of 0.5 mL per injection x 10 injections for a total of 2 x 10\^8 (200 million) Auto-hMSCs. The injections will be administered transendocardially during cardiac catheterization using the Biocardia Helical Infusion Catheter.	15
Total	30

Baseline characteristics

Characteristic	Auto-hMSCs	Allo-hMSCs	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	10 Participants	6 Participants	16 Participants
Age, Categorical Between 18 and 65 years	5 Participants	9 Participants	14 Participants
Age, Continuous	63.7 years STANDARD_DEVIATION 9.3	62.8 years STANDARD_DEVIATION 10.5	63.2 years STANDARD_DEVIATION 9.7
Region of Enrollment United States	15 participants	15 participants	30 participants
Sex: Female, Male Female	2 Participants	2 Participants	4 Participants
Sex: Female, Male Male	13 Participants	13 Participants	26 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	10 / 15	11 / 15
serious Total, serious adverse events	5 / 15	8 / 15

Outcome results

Primary

Incidence of TE-SAE Define as Composite of Death, Non-fatal MI, Stroke, Hospitalization for Worsening Heart Failure, Cardiac Perforation, Pericardial Tamponade, Ventricular Arrhythmias >15 Sec. or With Hemodynamic Compromise or Atrial Fibrillation

Time frame: One month post-catheterization

Arm	Measure	Value (NUMBER)
Allo-hMSCs	Incidence of TE-SAE Define as Composite of Death, Non-fatal MI, Stroke, Hospitalization for Worsening Heart Failure, Cardiac Perforation, Pericardial Tamponade, Ventricular Arrhythmias >15 Sec. or With Hemodynamic Compromise or Atrial Fibrillation	6.70 percentage of participants
Auto-hMSCs	Incidence of TE-SAE Define as Composite of Death, Non-fatal MI, Stroke, Hospitalization for Worsening Heart Failure, Cardiac Perforation, Pericardial Tamponade, Ventricular Arrhythmias >15 Sec. or With Hemodynamic Compromise or Atrial Fibrillation	6.70 percentage of participants

p-value: 1Fisher Exact

Secondary

Change in Distance Walked in 6-minutes From Baseline.

Time frame: 12-months

Arm	Measure	Value (MEAN)
Allo-hMSCs	Change in Distance Walked in 6-minutes From Baseline.	19.7 meters
Auto-hMSCs	Change in Distance Walked in 6-minutes From Baseline.	65.8 meters

p-value: 0.87Repeated measures ANOVA

Secondary

Change in Minnesota Living With Heart Failure Total Score

The Minnesota living with heart failure questionnaire uses a 6-point, zero to five, Likert scale. The total score is the sum of the 21 responses. The total score is considered the best measure of how heart failure and treatments impact a patients quality of life. The max score is 105, minimum score is 0. A lower score is considered a better quality of life.

Time frame: 12 months

Arm	Measure	Value (MEAN)
Allo-hMSCs	Change in Minnesota Living With Heart Failure Total Score	-10.2 units on a scale
Auto-hMSCs	Change in Minnesota Living With Heart Failure Total Score	-13.0 units on a scale

p-value: 0.84Repeated measures ANOVA

Secondary

Change in New York Heart Association Class at 12-months

Time frame: 12 months

Arm	Measure	Group	Value (NUMBER)
Allo-hMSCs	Change in New York Heart Association Class at 12-months	Improved NYHA Class	4 participants
Allo-hMSCs	Change in New York Heart Association Class at 12-months	No change in NYHA Class	8 participants
Allo-hMSCs	Change in New York Heart Association Class at 12-months	Worsened NYHA Class	2 participants
Auto-hMSCs	Change in New York Heart Association Class at 12-months	Improved NYHA Class	7 participants
Auto-hMSCs	Change in New York Heart Association Class at 12-months	No change in NYHA Class	6 participants
Auto-hMSCs	Change in New York Heart Association Class at 12-months	Worsened NYHA Class	1 participants

p-value: 0.55Chi-squared

Secondary