A Danish, Double-blind, Randomized Placebo-controlled Clinical Trial Evaluating Allogeneic Adipose Tissue Derived Mesenchymal Stromal Cell Therapy in Patients With Recently Diagnosed Non-ishemic Heart Failure With Reduced Ejection Fraction
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Change in left ventricular ejection fraction (I)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients above 18 years of age
- •Written informed consent
- •Anticipated to be able to participate during the entire study period
- •Diagnosed with non-ischemic heart failure with initial LVEF ≤ 40% and then up-titrated to maximal tolerable heart failure medication within the last 12 months
- •Symptomatic heart failure (NYHA II-III)
- •LVEF ≤ 45 % documented by echocardiography, CT or MRI performed after up-titration of heart failure medication (documentation of reduced LVEF at least after 1 and 3 months if implantation of a device either an Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronisation Therapy (CRT), respectively)
- •Plasma Pro-BNP > 300 pg/ml (> 35 pmol/L) in patients with sinus rhythm and plasma Pro-BNP > 422 pg/ml (> 49 pmol/L) in patients with atrial fibrillation.
排除标准
- •NYHA I or IV heart failure
- •Documented ischemic heart failure
- •On-going alcohol abuse
- •Implantation of CRT within 3 months or ICD within 1 month
- •Acute coronary syndrome with elevation of CKMB (Creatine Phosphatase-Myocardial Band) or troponins, stroke or transitory cerebral ischemia within six weeks of inclusion
- •Expected to undergo screening for heart transplantation during the study time
- •Listed for heart transplantation
- •Other cardiac revascularization treatments to be performed
- •Moderate to severe aortic stenosis (valve area < 1.1 cm2) or clinically significant mitral valve disease
- •Diminished functional capacity for other reasons such as: chronic obstructive pulmonary disease (COPD) with forced expiratory volume (FEV) < 1 L/min or body mass index > 35kg/m2
- •Clinically significant anaemia (haemoglobin < 6 mmol/L), leukopenia (leucocytes < 2 109/L), leucocytosis (leucocytes >14 109/L) or thrombocytopenia (thrombocytes < 50 109/L)
- •History with malignant disease within five years of inclusion or current suspected malignancy - except treated skin cancer other than melanoma
- •Patients with known hypersensitivity to DMSO and Dextran-
- •Pregnant women
- •Other experimental treatment within four weeks from baseline tests
- •Participation in another interventional trial
研究组 & 干预措施
Allogeneic adipose tissue-derived mesenchymal stromal cells (C2C_ASC110)
Intravenous infusion of allogeneic adipose tissue-derived mesenchymal stromal cells (C2C_ASC110) 1 month apart.
干预措施: Allogeneic adipose tissue-derived mesenchymal stem cells (Drug)
CryoStor® CS10
Intravenous infusion of CryoStor® CS10 1 month apart.
干预措施: Cryostor CS10 (Other)
结局指标
主要结局
Change in left ventricular ejection fraction (I)
时间窗: From enrollment to 6 months after the last infusion of C2C_ASC110 and placebo.
Change in left ventricular ejection fraction 6 months after last C2C\_ASC110 infusion compared to the placebo group.
次要结局
- Changes in left ventricular end systolic volume(From enrollment to 7 months and to 12 months.)
- Change in left ventricular ejection fraction (II)(From enrollment to 7 months and to 12 months.)
- Changes in left ventricular end diastolic volume(From enrollment to 7 months and to 12 months.)
- Change in NYHA classification(From enrollment to 12 months.)
- Change in KCCQ questionnaire score(From enrollment to 12 months.)
- Change in EQ5D5L questionnaire score(From enrollment to 12 months.)
- Change in 6 minutes walking test(From enrollment to 12 months.)
- Change in Pro-BNP(From enrollment to 12 months.)
- Incidence and severity of adverse reactions(From the first infusion of C2C_ASC110 and placebo to 12 months.)