- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03797092
Stem Cell Therapy in Non-IschEmic Non-treatable Dilated CardiomyopathiEs II: a Pilot Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study design
The primary objective of the study is to investigate safety and regenerative capacity of direct intra-myocardial injection of 100 million allogeneic CSCC_ASCs in NIDCM patients with reduced left ventricular EF (≤ 40%) and heart failure.
It is a proof of concept study enrolling a total of 30 NIDCM patients with heart failure who will be randomly allocated in a 2:1 ratio to either CSCC_ASC cell therapy (Stem Cell Group) or no cell therapy (Control Group). The treatment period is estimated to be 6 months (efficacy end-point) with a 12-month follow-up period for safety end-points.
Patient treatment and follow-up
- The cell IMP will be delivered by a courier service to from REGIONH to UKCL using validated portable dry liquid nitrogen shipping containers. It will then be stored in nitrogen vapour containers until treatment.
- The preparation of the IMP will be performed as described in the treatment manual. The IMP will be thawed and prepared for injection immediately before treatment.
- A 3-D map of the left ventricle will be created using the NOGA XP® system (Biological Delivery System, Cordis, Johnson & Johnson, USA). The delivery of the IMP (100 million ASCs) into the myocardium will be performed by 10-15 injections of 0.2 cc, as described in the treatment manual.
- The post cell therapy surveillance will include clinical and laboratory safety follow-up with monitoring of cardiac enzymes, hemodynamic and rhythm stability. The clinical follow-up will be obtained at pre-defined time points. The presence of allogeneic HLA anti-bodies will be monitored three and six months after treatment. End-points will be monitored continuously and reported as occurring throughout the 12 months follow-up period.
Primary and secondary endpoints
The primary endpoint is change in left ventricle end-systolic volume (LVESV) at 6 months follow-up measured by Echocardiography.
The secondary endpoints are safety evaluated by development of allogeneic antibodies and laboratory safety measurements 1, 3 and 6 months after treatment and changes in left ventricular ejection fraction (LVEF), end-diastolic volume and myocardial mass at 6 months follow-up.
Additional secondary endpoints are changes in NYHA, Kansas City Cardiomyopathy Questionnaire, EQ-5D3L Questionnaire, 6 min walking test, additional echocardiographic measures (Global strain %) and NT-pro-BNP.
Safety of allogeneic CSCC_ASCs with respect to incidence and severity of serious adverse events and suspected unrelated serious adverse events will be evaluated at 12 months follow-up.
Outcome measures for safety Safety endpoints will be collected, reported to the authorities and monitored according to legislation during the entire study period.
Adverse event (AE) is defined as any untoward medical occurrence in a subject who was treated with an investigational product, and does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease, whether or not related to the investigational product.
Serious adverse event (SAE) is defined as any untoward medical occurrence that:
- results in death
- is life-threatening
- requires inpatient hospitalisation or prolongation of existing hospitalisation
- results in persistent or significant disability/incapacity
- is a congenital anomaly/birth defect
- is medically important
Suspected unexpected serious adverse event reactions (SUSAR) is defined as a SAE occurring in a subject in an interventional study that is assessed as both causally related to the suspect product under clinical investigation and unexpected per the Investigator's Brochure (IB).
An independent Data Safety Monitoring Board (DSMB) will be established to evaluate the safety of the treatment. The DSMB will report directly to the director of the Project Management Board, which will take the necessary action upon the DSMB's recommendations.
Study medication The investigational cell product, CSCC_ASC, will be produced in an approved GMP facility in Cardiology Stem Cell Centre at Rigshospitalet University Hospital, Copenhagen, Denmark.
The production of the allogeneic CSCC_ASCs will follow the description in an approved Investigational Medicinal Product Dossier. The cell product will come from healthy donors.
The production unit will label the investigational medicinal product (IMP) in accordance with the legislation and keep the randomisation code until finalisation of the clinical trial. The final cell products will be stored in nitrogen vapour containers until clinical use.
Allogeneic MSCs and ASCs have been administered to more than 600 patients with heart disease. In the conducted clinical trials there has not been any serious adverse event due to the treatment. A few patients have developed transient donor specific HLA-antibodies in serum within the first months after treatment. However, none of the patients had any symptoms related to the presence of antibodies. Transient fever was registered in a few patients, but it could as well be due to the treatment procedure or the disease for treatment.
Based on the accumulated safety and efficacy evidence with clinical use of allogeneic MSCs and ASCs in conducted clinical trials and the safety data from the CSCC_ASC phase I trial and the two ongoing phase II trials then it is concluded that it is safe to conduct a pilot CSCC_ASC trial in patients with NIDCM and HF.
Echocardiography
The echocardiography data will be recorded at pre-defined intervals according to American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) recommendations. For each patient at least five end-expiratory full cardiac cycles will be recorded for each protocol specified view. All acquired images will be de-identified and transferred to independent imaging core-lab (Stanford Cardiovascular Institute Clinical Biomarker & Phenotyping Core Lab). The recordings will be analyzed at the end of the study by an independent echocardiographer who will be blinded to the patient's treatment status and the timing of the recordings. All measurements will be performed according to ASE/EACVI recommendations. All echocardiographic measurements will be averaged over 5 cardiac cycles. Left ventricular end-systolic dimension (LVESD) and end-diastolic dimension (LVEDD) will be measured in the parasternal long-axis view. Left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and LVEF will be estimated using the Simpson's biplane method. Peak longitudinal strains will be computed automatically to generate regional data from each of the 17 segments and then averaged to calculate global longitudinal strain.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Jens Kastrup, MD, DMSc
- Phone Number: 004535452819
- Email: jens.akstrup@regionh.dk
Study Contact Backup
- Name: Abbas A Qayyum, MD, PhD
- Phone Number: 004535451076
- Email: abbas.ali.qayyum@regionh.dk
Study Locations
-
-
-
Copenhagen, Denmark, 2100
- Recruiting
- The Heart Centre, Rigshospitalet University Hospital Copenhagen,
-
Principal Investigator:
- Jens Kastrup, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 30 to 80 years of age
- Signed informed consent
- Patients with non-ischemic dilated cardiomyopathy
- NYHA ≥ II in spite of optimal heart failure treatment and have no other treatment options
- Heart failure medication unchanged two months prior to inclusion/signature of informed consent. Changes in diuretics accepted
- LVEF ≤ 405%
- Plasma NT-pro-BNP > 300 pg/ml (> 35 pmol/L)
- Patients cannot be included until three months after implantation of a cardiac resynchronisation therapy device (CRTD) and until 1 month after an ICD unit
Exclusion Criteria:
- Heart Failure NYHA I
- Moderate to severe aortic stenosis (valve area < 1.3 cm2) or valvular disease with option for surgery or interventional therapy.
- Heart failure caused by cardiac valve disease or untreated hypertension.
- If the patient is expected to be candidate for MitraClip therapy of mitral regurgitation in the 12 months follow-up period.
- Cardiomyopathy with 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
- 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
- Clinical significant anaemia (haemoglobin < 6 mmol/L), leukopenia (leucocytes < 2 109/L), leucocytosis (leucocytes > 14 109/L) or thrombocytopenia (thrombocytes < 50 109/L)
- Reduced kidney function (eGFR < 30 ml/min)
- Left ventricular thrombus
- Anticoagulation treatment that cannot be paused during cell injections.
- Patients with reduced immune response
- History with malignant disease within five years of inclusion or suspected malignity - except treated skin cancer other than melanoma
- Pregnant women
- Woman of childbearing potential unless βHCG negative and they should be on contraception during the trial
- Other experimental treatment within four weeks of baseline tests
- Participation in another intervention trial
- Life expectancy less than one year
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
No Intervention: Control group
No treatment
|
|
Active Comparator: Active
Allogeneic adipose-derived stromal cells (CSCC_ASC)
|
Active group
Other Names:
No treatment
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Left ventricle end-systolic volume
Time Frame: 6 months after treatment
|
Measured using echocardiography
|
6 months after treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Allogeneic antibodies
Time Frame: Up to 12 months after treatment
|
Development of allogeneic antibodies and laboratory safety measurements 1, 3 and 6 months after treatment
|
Up to 12 months after treatment
|
Left ventricular ejection fraction
Time Frame: 6 months after treatment
|
Changes in LVEF
|
6 months after treatment
|
Myocardial mass of left ventricle
Time Frame: 6 months after treatment
|
Change in echo measured global myocardial mass
|
6 months after treatment
|
NYHA
Time Frame: 6 months after treatment
|
Symptoms
|
6 months after treatment
|
Kansas City Cardiomyopathy Questionnaire
Time Frame: 6 months after treatment
|
Questionnaire
|
6 months after treatment
|
EQ-5D3L Questionnaire
Time Frame: 6 months after treatment
|
Questionnaire
|
6 months after treatment
|
6 min walking test
Time Frame: 6 months
|
Test
|
6 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Bojan Vrtovec, MD, PhD, Dep. of Cardiology, Uni. Medical Center Ljubljana, Slovenia
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SCIENCE II - Pilot
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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