Use of Bone Marrow Derived Stem Cell and G-CSF With Circulatory Assistance in the Treatment of DCM

Study Overview
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Brief Summary
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DCM Support is recruiting patients with dilated cardiomyopathy and heart failure symptoms. The goal of this clinical trial is to examine whether treatment with a patient's own stem cells can improve their heart function and alleviate heart failure symptoms. Stem cells will be collected from bone marrow in the patient's hip under local anaesthetic. The stem cells will be infused into the arteries that supply blood to the heart under local anaesthetic. A mini heart pump will be used to take the strain off the heart during the procedure. The follow-up involves a phone call at 1 month and clinic visits at 3 and 12 months

Detailed Description
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DCM SUPPORT is a single centre, single arm clinical trial taking place at St Bartholomew's Hospital in London, UK. It is recruiting patients with dilated cardiomyopathy and ongoing heart failure symptoms All patients undergo a bone marrow aspiration after 5 days of subcutaneous G-CSF injections After cell processing, bone marrow-derived mononuclear cells are infused into the coronary arteries using the stop-flow technique. An intra-procedural Impella CP device is used to support the circulation. The primary endpoint is change in left ventricular ejection fraction at 3 months as measured by cardiac CT.

Official Title
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Phase II Study Assessing the Combined Use of Autologous Bone Marrow Derived Mononuclear Cells and G-csf With Percutaneous Circulatory Assistance in the Treatment of Dilated Cardiomyopathy

Conditions
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Dilated Cardiomyopathy

Intervention / Treatment
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* Biological: Bone marrow derived mononuclear cells and G-CSF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a confirmed diagnosis of dilated cardiomyopathy under the supervision of a physician or a heart failure nurse specialist. NYHA class ≥ 2 symptoms despite having received optimal medical therapy and appropriate device therapy, as per clinical guidelines for an interval of at least 3 months. No other treatment options available as part of the current best standard of care. LVEF ≤35% on any imaging modality performed as part of the screening phase. Exclusion Criteria: Congenital heart disease. Clinically significant valvular heart disease. Patients who are not suitable for a Percutaneous Mechanical Support Device (E.g. unsuitable femoral artery anatomy, unable able to lie flat for prolonged time to accommodate the stem cell infusion & presence of LV thrombus) Weight of patient that exceeds the maximum limit of the cardiac catheterisation laboratory table / CT scanner. Cardiomyopathy 2o to a reversible cause that has not been treated e.g. thyroid disease, alcohol abuse, hypophosphataemia, hypocalcaemia, cocaine abuse, selenium toxicity & chronic uncontrolled tachycardia. Cardiomyopathy in association with a neuromuscular disorder e.g. Duchenne's progressive muscular dystrophy. Previous cardiac surgery. Contra-indication for bone marrow aspiration (thrombocytopaenia - platelet count <80 x 10(9)/L or extensive surgical scarring/anatomical deformity at site of bone marrow puncture). Known active infection on admission as defined by a temperature >37.5°C or on a short course of antibiotics. An active infection of hepatitis B, hepatitis C, syphilis or HTLV Known HIV infection Chronic inflammatory disease requiring on-going medication. Concomitant disease with a life expectancy of less than one year Follow-up impossible (no fixed abode, etc.) Neoplastic disease without documented remission within the past 5 years. Patients on renal replacement therapy. Subjects of childbearing potential unless βHCG negative and are on adequate contraception during the trial. Patients falling into the vulnerable category or lacking capacity Patients who are unable to understand or read written English will be excluded from the trial. Killip Class III or above

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single arm intervention study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: BMMNC intervention arm<br>Bone marrow derived mononuclear cells and G-CSF | Biological: Bone marrow derived mononuclear cells and G-CSF<br>* Intra-coronary infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left ventricular ejection fraction | Change in left ventricular ejection fraction as measured by cardiac CT | Baseline to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left ventricular ejection fraction | Change in left ventricular ejection fraction as measured by cardiac CT | Baseline to 12 months | 
| Change in exercise capacity | Change in exercise capacity as assessed by a 6-minute walk test | Baseline to 3 and 12 months | 
| Change in heart failure symptoms | Change in heart failure symptoms as measured by NYHA classification | Baseline to 3 and 12 months | 
| Change in quality of life as assessed by Minnesota Living with Heart Failure Questionnaire scores | Change in quality of life as measured by MLHFQ (The 21-item MLHFQ uses a 6-point Likert scale, where 0 = no, 1= very little and 5= very much. The questions are intended to be representative of the ways heart failure can affect physical and emotional dimensions of quality of life) | Baseline to 3 and 12 months | 
| Change in quality of life as measured by EuroQol-5 Dimension 5 Levels questionnaires | Change in quality of life as measured by EQ-5D-5L questionnaires (the scale measures quality of life on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) | Baseline to 3 and 12 months | 
| Procedural safety as assessed by in-hospital procedural related morbidity/mortality | Procedural safety as assessed by in-hospital procedural related morbidity/mortality | In-hospital procedural time | 
| Change in biochemical markers of heart failure | Change in biochemical markers of heart failure as measured by change in NT-proBNP | Baseline to 3 and 12 months | 
| Assessment of rates of MACE (cumulative & individual components) | Rates of MACE (all-cause death, myocardial infarction, hospitalisation for heart failure, major arrhythmias [defined as VT and VF]) | 3 and 12 months | 
| Assessment of rates of stroke | Assessment of rates of stroke | 3 and 12 months | 
| Assessment of peri-procedural myocardial infarction | Assessment of peri-procedural myocardial infarction as per SCAI definition measured by change in troponin (MI defined by increase in troponin >70 times upper limit of normal from baseline). | Day 0 and Day 6 | 
| Change in renal function | Change in renal function from baseline at 3 and 12 months as measured by creatinine levels. | Baseline to 3 and 12 months | 
| Change in inflammatory markers | Change in inflammatory markers as measured by change in C-reactive protein | Baseline to 3 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem Cell, Circulatory Support, Heart Failure, G-CSF