Allogeneic Stem Cell Therapy in Heart Failure (CSCC_ASCII)

Allogeneic Adipose Tissue-derived Stromal/Stem Cell Therapy in Patients With Ischemic Heart Disease and Heart Failure: A Phase II Danish Multicentre Study

The present aim is to perform at clinical double-blind placebo-controlled Cardiology Stem Cell Centre - Adipose Stem Cells (CSCC_ASC) study in heart failure patients to investigate the regenerative capacity of the CSCC_ASC treatment.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Biological: Placebo; Biological: Cardiology Stem Cell Centre Adipose Stem Cell (CSCC_ASC)

Detailed Description

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 Ejection Fraction (EF) (≤45%) and heart failure in a double-blind placebo-controlled design.

A total of 81 patients with will be enrolled in the study and treated in a 2:1 randomization with either CSCC_ASC or placebo (saline).

The primary endpoint is change in left ventricle end-systolic volume (LVESV) at 6 months follow-up.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen Ø, Denmark, 2100
    • Cardiac Catheterization Laboratory 2014, 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%
6. Plasma NT-pro-BNP > 300 pg/ml (> 35 pmol/L) in sinus rhythm and plasma NT-pro-BNP > 422 pg/ml (> 450 pmol/L) in patients with atrial fibrillation
7. Maximal tolerable heart failure medication
8. Medication unchanged two months prior to inclusion
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 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

Exclusion Criteria:

1. Heart Failure (NYHA I or IV)
2. Acute coronary syndrome with elevation of creatine kinase (CK) isoenzyme MB (CKMB) or troponins, stroke or transitory cerebral ischemia within six weeks of inclusion
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 mm2) or valvular disease with option for surgery.
6. 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
7. Clinical significant anaemia (haemoglobin < 6 mmol/L), leukopenia (leucocytes < 2 109/L), leucocytosis (leucocytes >14 109/L) or thrombocytopenia (thrombocytes < 50 109/L)
8. Anticoagulation treatment that cannot be paused during cell injections
9. Patients with reduced immune response
10. History with malignant disease within five years of inclusion or suspected malignity - except treated skin cancer other than melanoma
11. Pregnant women
12. Other experimental treatment within four weeks of baseline tests
13. Participation in another intervention trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Saline	Biological: Placebo; Saline
ACTIVE_COMPARATOR: Cardiology Stem Cell Centre Adipose Stem Cell (CSCC_ASC); Allogeneic adipose derived stromal cells	Biological: Cardiology Stem Cell Centre Adipose Stem Cell (CSCC_ASC); Direct intramyocardial injection of CSCC_ASC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in left ventricle end-systolic volume (LVESV) from base line to 6 months follow-up measured by echocardiography and computerized tomography	change in left ventricle end-systolic volume (LVESV) from base line to 6 months follow-up measured by echocardiography and computerized tomography	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Safety is evaluated by the incidence and severity of serious adverse events and suspected unrelated serious adverse events at 12 months follow-up	12 months
Efficacy left ventricle	change in left ventricle ejection fraction (EF) measured by echocardiography and computerized tomography	6 months
Efficacy clinical function assessed by change in Kansas City Cardiomyopathy Questionnaire (KCCQ) from baseline to 6 months follow-up	change in Kansas City Cardiomyopathy Questionnaire (KCCQ) from baseline to 6 months follow-up	6 months
Efficacy clinical function assessed by change in Seattle Angina Questionnaire and 6 min walking test from baseline to 6 months follow-up	change in Seattle Angina Questionnaire and 6 min walking test from baseline to 6 months follow-up	6 months
Efficacy clinical function assessed by change in 6 min walking test from baseline to 6 months follow-up	change in 6 min walking test from baseline to 6 months follow-up	6 months
Efficacy clinical function assessed by change in Kansas City Cardiomyopathy Questionnaire (KCCQ) from baseline to 12 months follow-up	change in Kansas City Cardiomyopathy Questionnaire (KCCQ) from baseline to 12 months follow-up	12 months
Efficacy clinical function assessed by change in Seattle Angina Questionnaire and 6 min walking test from baseline to 12 months follow-up	change in Seattle Angina Questionnaire and 6 min walking test from baseline to 12 months follow-up	12 months
Efficacy clinical function assessed by change in 6 min walking test from baseline to 12 months follow-up	change in 6 min walking test from baseline to 12 months follow-up	12 months

Collaborators and Investigators

• Sponsor: JKastrup

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2015
• Primary Completion (ACTUAL): July 1, 2021
• Study Completion (ACTUAL): July 1, 2022

Study Registration Dates

• First Submitted: July 20, 2015
• First Submitted That Met QC Criteria: March 24, 2017
• First Posted (ACTUAL): March 27, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 6, 2022
• Last Update Submitted That Met QC Criteria: September 2, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CSCC_ASCII

Plan for Individual participant data (IPD)

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