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

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

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

Study Overview

• Status: Recruiting
• Conditions: Dilated Cardiomyopathy
• Intervention / Treatment: Biological: Bone marrow derived mononuclear cells and G-CSF

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anthony Mathur; Phone Number: 0203 765 8704; Email: a.mathur@qmul.ac.uk
• Study Contact Backup: Name: Sonia Bastos; Phone Number: 0203 765 8704; Email: s.bastos@nhs.net

Study Locations

• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • Recruiting
    • St Bartholomew'S Hospital
    • Contact: Sonia Bastos; Phone Number: 0203 765 8704; Email: s.bastos@nhs.net
    • Contact: Alice Reid; Email: a.e.reid@qmul.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Barts & The London NHS Trust
• Investigators: Principal Investigator: Anthony Mathur, Queen Mary University of London

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2018
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): March 30, 2025

Study Registration Dates

• First Submitted: March 29, 2018
• First Submitted That Met QC Criteria: June 19, 2018
• First Posted (Actual): June 28, 2018

Study Record Updates

• Last Update Posted (Estimated): June 16, 2023
• Last Update Submitted That Met QC Criteria: June 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Heart Failure; Stem Cell; G-CSF; Circulatory Support
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Cardiomegaly; Laminopathies; Cardiomyopathies; Cardiomyopathy, Dilated
• Other Study ID Numbers: Reda 012357; 2018-001063-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No