The goal of this clinical trial is to investigate the efficacy and safety of intravenous infusions of allogeneic adipose tissue-derived mesechymal stromal cells in patients with recently diagnosed non-ischemic heart failure in restoring cardiac function compared to placebo. The primary outcome of this trial is the change in left ventricular ejection fraction 6 month after treatment compared to placebo. Participants will be given two treatments with one month apart of either allogeneic adipose tissue-derived mesechymal stromal cells or placebo.
Non-ischemic heart failure (NIHF) is the leading reason for heart transplantation. The disease can be caused by several different factors, which include genetic disposition, inflammation, hypertension, alcohol consumption, and arrhythmia. Regardless of the aetiology, immune activation in myocardium leads to collagen deposition and decreases the function of heart. There are currently no treatment options, which reverse the inflammatory component in NIHF. For the past decade, cell therapy has been tested as treatment option for ischemic and non-ischemic heart failure. Especially the mesenchymal stromal cell (MSC) has shown encouraging results for their potential to improve cardiac function in patients with non-ischemic heart failure along with its safety. The cardiac improvement may be related to the immunomodulation as MSC is known by its ability to modulate the immune system and has successfully been applied clinically as a novel active immunosuppressor. We aim to conduct a clinical trial in which patients recently diagnosed with NIHF will be randomized to either treatment with two intravenous infusions of allogeneic MSCs obtained from adipose tissue (C2C\_ASC110) or placebo (Cryostor® CS10) 4 weeks apart. The objective is to evaluate the safety and effect of MSCs on cardiac function. The long-term perspective is that the information gathered from this study can lead to a new treatment option for this specific group of patients, who currently have no further treatment options and a poor prognosis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
Two intravenous infusions of C2C\_ASC110 1 month apart. The C2C\_ASC110 product contains 110 million cells.
Two intravenous infusions of CryoStor CS10 1 month apart.
Cardiology Stem Cell Centre, Department of Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Denmark
Copenhagen, Denmark
Change in left ventricular ejection fraction (I)
Change in left ventricular ejection fraction 6 months after last C2C\_ASC110 infusion compared to the placebo group.
Time frame: From enrollment to 6 months after the last infusion of C2C_ASC110 and placebo.
Changes in left ventricular end systolic volume
Changes in left ventricular end systolic volume
Time frame: From enrollment to 7 months and to 12 months.
Change in left ventricular ejection fraction (II)
Change in left ventricular ejection fraction.
Time frame: From enrollment to 7 months and to 12 months.
Changes in left ventricular end diastolic volume
Changes in left ventricular end diastolic volume.
Time frame: From enrollment to 7 months and to 12 months.
Change in NYHA classification
Change in New York Heart Association (NYHA) classification. A scale from 1 to 4 describing the extent of heart failure by patient-reported symptoms, with class 1 denoting no symptoms and no limitations in ordinary physical activity and class 4 denoting symptoms and severe limitations in ordinary physical activity.
Time frame: From enrollment to 12 months.
Change in KCCQ questionnaire score
Change in Kansas City Cardiomyopathy (KCCQ) questionnaire score. A scale from 0 to 100 describing health status in patients with heart failure, with 0 denoting the worst possible health status and 100 denotes the best possible health status.
Time frame: From enrollment to 12 months.
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QUADRUPLE
Enrollment
90
Change in EQ5D5L questionnaire score
Change in European Quality of Life - 5 Dimensions (EQ5D5L) questionnaire score. A scale from 0 to 100 describing health related quality of life, with 0 denoting the worst possible quality of life and 100 denoting the best possible quality of life.
Time frame: From enrollment to 12 months.
Change in 6 minutes walking test
Change in 6 minutes walking test.
Time frame: From enrollment to 12 months.
Change in Pro-BNP
Change in Pro-BNP.
Time frame: From enrollment to 12 months.
Incidence and severity of adverse reactions
Incidence and severity of serious adverse reactions and suspected unexpected serious adverse reactions.
Time frame: From the first infusion of C2C_ASC110 and placebo to 12 months.