Stem Cell Therapy in IschEmic Non-treatable Cardiac Disease (SCIENCE)

Stem Cell Therapy in IschEmic Non-treatable Cardiac Disease - SCIENCE A European Multi-Centre Trial

The aim of the SCIENCE study is, in an international multicentre double-blind placebo-controlled study, to investigate efficacy of direct intra-myocardial injection of 100 mio. allogeneic Cardiology Stem Cell Centre_adipose derived stem cells (CSCC_ASCs) in patients with reduced left ventricular Ejection Fraction (EF) (≤45%) and heart failure.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Biological: CSCC_ASC

Detailed Description

The aim of the SCIENCE study is, in an international multicentre double-blind placebo-controlled study, to investigate efficacy of direct intra-myocardial injection of 100 mio. allogeneic Cardiology Stem Cell Centre_adipose derived stem cells (CSCC_ASCs) in patients with reduced left ventricular EF (≤45%) and heart failure.

The primary objective is to investigate the regenerative capacity of direct intra-myocardial injection of 100 mio. allogeneic CSCC_ASCs in patients with reduced left ventricular EF (≤45%) and heart failure in a double-blind placebo-controlled design.

A total of 138 patients with will be enrolled in the study and treated in a 2:1 randomization with either CSCC_ASC or placebo (saline).

• Study Type: Interventional
• Enrollment (Actual): 133
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • 2014 Department of Cardiology, The Heart Centre, University Hospital Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 30 to 80 years of age
2. Signed informed consent
3. Chronic stable ischemic heart disease
4. Symptomatic heart failure New York Heart Association (NYHA) class II-III
5. EF ≤ 45% on echocardiography, Computerized Tomography (CT) or Magnetic Resonances Imaging (MRI) scan
6. Plasma NT-pro-BNP > 300 pg/ml (> 35 pmol/L)
7. Maximal tolerable heart failure medication
8. Heart failure medication unchanged two months prior to inclusion. Changes in diuretics accepted.
9. No option for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)
10. Patients who have had PCI or CABG within six months of inclusion must have a new coronary angiography less than one month before inclusion or at least four months after the intervention to rule out early restenosis
11. Patients cannot be included until three months after implantation of a cardiac resynchronisation therapy device (CRTD) and until 1 month after an ICD unit

Exclusion Criteria:

1. Heart Failure (NYHA class I or IV)
2. Acute coronary syndrome with acute reversible elevation of CKMB or troponins, stroke or transitory cerebral ischemia within six weeks of inclusion. Constant elevated troponin due to renal failure, heart failure etc. do not exclude the patient.
3. Other revascularisation treatment within four months of treatment
4. If clinically indicated the patient should have a coronary angiography before inclusion
5. Moderate to severe aortic stenosis (valve area < 1.3 cm2) or valvular disease with option for surgery or interventional therapy.
6. Aortic valve replacement with an artificial heart valve. However, a trans-septal treatment approach can be considered in these patients.
7. If the patient is expected to be candidate for MitraClip therapy of mitral regurgitation in the 12 months follow-up period.
8. Diminished functional capacity for other reasons such as: obstructive pulmonary disease (COPD) with forced expiratory volume (FEV) <1 L/min, moderate to severe claudication or morbid obesity
9. Clinical significant anaemia (haemoglobin < 6 mmol/L), leukopenia (leucocytes < 2 109/L), leucocytosis (leucocytes > 14 109/L) or thrombocytopenia (thrombocytes < 50 109/L)
10. Reduced kidney function (estimated Glomerular Filtration Rate (eGFR) < 30 ml/min)
11. Left ventricular thrombus
12. Anticoagulation treatment that cannot be paused during cell injections. Patients can continue with platelet inhibitor treatment
13. Patients with reduced immune response or known anti-HLA (human leukocyte antigen) antibodies
14. History with malignant disease within five years of inclusion or suspected malignity - except treated skin cancer other than melanoma
15. Pregnant women
16. Other experimental treatment within four weeks of baseline tests
17. Participation in another intervention trial
18. Life expectancy less than one year
19. Known hypersensitivity to Dimethyl sulfoxide (DMSO), penicillin and streptomycin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Saline	Biological: CSCC_ASC; The stem cells will be injected directly into the myocardium using the NOGA XP system (BDS, US); Other Names: Cardiology Stem Cell Centre_adipose derived stem cells
Active Comparator: CSCC_ASC; Cardiology Stem Cell Centre_adipose derived stem cells (CSCC_ASC)	Biological: CSCC_ASC; The stem cells will be injected directly into the myocardium using the NOGA XP system (BDS, US); Other Names: Cardiology Stem Cell Centre_adipose derived stem cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
left ventricle end-systolic volume (LVESV)	The primary endpoint is change in left ventricle end-systolic volume (LVESV) from baseline to 6 months follow-up measured by ECHO, MR and CT between CSCC_ASC and placebo treated	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety - Serious adverse events	Incidence and severity of serious adverse events and suspected unrelated serious adverse events 12 months follow-up	6 months

Collaborators and Investigators

• Sponsor: JKastrup
• Collaborators: European Union
• Investigators: Principal Investigator: Jens Kastrup, Professor MD, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: February 1, 2016
• First Submitted That Met QC Criteria: February 2, 2016
• First Posted (Estimate): February 3, 2016

Study Record Updates

• Last Update Posted (Actual): January 19, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Heart failure; ischemic heart disease; stem cell; Stem cell therapy; adipose derived stem cell
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Failure; Heart Diseases
• Other Study ID Numbers: SCIENCE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data can be shared for Scientific collaboration