Ignite Creation Date:
2025-12-24 @ 3:54 PM
Ignite Modification Date:
2025-12-24 @ 3:54 PM
Study NCT ID:
NCT03797092
Status:
UNKNOWN
Last Update Posted:
2021-01-19
First Post:
2018-06-28
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Stem Cell Therapy in Non-IschEmic Non-treatable Dilated CardiomyopathiEs II: a Pilot Study
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006333', 'term': 'Heart Failure'}], 'ancestors': [{'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D035061', 'term': 'Control Groups'}], 'ancestors': [{'id': 'D015340', 'term': 'Epidemiologic Research Design'}, {'id': 'D004812', 'term': 'Epidemiologic Methods'}, {'id': 'D008919', 'term': 'Investigative Techniques'}, {'id': 'D012107', 'term': 'Research Design'}, {'id': 'D008722', 'term': 'Methods'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR'], 'maskingDescription': 'The patients will be randomized to either IMP or control in a 2:1 randomization.\n\nThe outcome ECHO investigations will be analyzed blinded by an independent core lab.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Open randomized treatment group and control group clinical trial'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 30}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2019-10-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-01', 'completionDateStruct': {'date': '2021-09-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2021-01-15', 'studyFirstSubmitDate': '2018-06-28', 'studyFirstSubmitQcDate': '2019-01-07', 'lastUpdatePostDateStruct': {'date': '2021-01-19', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-01-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-07-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Left ventricle end-systolic volume', 'timeFrame': '6 months after treatment', 'description': 'Measured using echocardiography'}], 'secondaryOutcomes': [{'measure': 'Allogeneic antibodies', 'timeFrame': 'Up to 12 months after treatment', 'description': 'Development of allogeneic antibodies and laboratory safety measurements 1, 3 and 6 months after treatment'}, {'measure': 'Left ventricular ejection fraction', 'timeFrame': '6 months after treatment', 'description': 'Changes in LVEF'}, {'measure': 'Myocardial mass of left ventricle', 'timeFrame': '6 months after treatment', 'description': 'Change in echo measured global myocardial mass'}, {'measure': 'NYHA', 'timeFrame': '6 months after treatment', 'description': 'Symptoms'}, {'measure': 'Kansas City Cardiomyopathy Questionnaire', 'timeFrame': '6 months after treatment', 'description': 'Questionnaire'}, {'measure': 'EQ-5D3L Questionnaire', 'timeFrame': '6 months after treatment', 'description': 'Questionnaire'}, {'measure': '6 min walking test', 'timeFrame': '6 months', 'description': 'Test'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Stem cell therapy', 'Heart failure', 'Clinical trial', 'Allogeneic'], 'conditions': ['Non-ischemic Dilated Cardiomyopathy']}, 'referencesModule': {'references': [{'pmid': '28880460', 'type': 'RESULT', 'citation': 'Kastrup J, Haack-Sorensen M, Juhl M, Harary Sondergaard R, Follin B, Drozd Lund L, Monsted Johansen E, Ali Qayyum A, Bruun Mathiasen A, Jorgensen E, Helqvist S, Jorgen Elberg J, Bruunsgaard H, Ekblond A. Cryopreserved Off-the-Shelf Allogeneic Adipose-Derived Stromal Cells for Therapy in Patients with Ischemic Heart Disease and Heart Failure-A Safety Study. Stem Cells Transl Med. 2017 Nov;6(11):1963-1971. doi: 10.1002/sctm.17-0040. Epub 2017 Sep 7.'}], 'seeAlsoLinks': [{'url': 'https://www.ncbi.nlm.nih.gov/pubmed/28880460', 'label': 'PubMed abstract related to the used allogeneic stem cell product'}]}, 'descriptionModule': {'briefSummary': 'The overall aim of the project is to test the feasibility and safety of allogeneic adipose-derived stromal cells (CSCC\\_ASC) investigational medicinal product, to improve myocardial function in patients with non-ischemic dilated cardiomyopathies (NIDCM) and heart failure.', 'detailedDescription': "Study design\n\nThe 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.\n\nIt 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.\n\nPatient treatment and follow-up\n\n* 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.\n* 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.\n* 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.\n* 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.\n\nPrimary and secondary endpoints\n\nThe primary endpoint is change in left ventricle end-systolic volume (LVESV) at 6 months follow-up measured by Echocardiography.\n\nThe 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.\n\nAdditional 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.\n\nSafety 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.\n\nOutcome measures for safety Safety endpoints will be collected, reported to the authorities and monitored according to legislation during the entire study period.\n\nAdverse 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.\n\nSerious adverse event (SAE) is defined as any untoward medical occurrence that:\n\n1. results in death\n2. is life-threatening\n3. requires inpatient hospitalisation or prolongation of existing hospitalisation\n4. results in persistent or significant disability/incapacity\n5. is a congenital anomaly/birth defect\n6. is medically important\n\nSuspected 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).\n\nAn 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.\n\nStudy 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.\n\nThe 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.\n\nThe 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.\n\nAllogeneic 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.\n\nBased 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.\n\nEchocardiography\n\nThe 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."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '30 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. 30 to 80 years of age\n2. Signed informed consent\n3. Patients with non-ischemic dilated cardiomyopathy\n4. NYHA ≥ II in spite of optimal heart failure treatment and have no other treatment options\n5. Heart failure medication unchanged two months prior to inclusion/signature of informed consent. Changes in diuretics accepted\n6. LVEF ≤ 405%\n7. Plasma NT-pro-BNP \\> 300 pg/ml (\\> 35 pmol/L)\n8. Patients cannot be included until three months after implantation of a cardiac resynchronisation therapy device (CRTD) and until 1 month after an ICD unit\n\nExclusion Criteria:\n\n1. Heart Failure NYHA I\n2. Moderate to severe aortic stenosis (valve area \\< 1.3 cm2) or valvular disease with option for surgery or interventional therapy.\n3. Heart failure caused by cardiac valve disease or untreated hypertension.\n4. If the patient is expected to be candidate for MitraClip therapy of mitral regurgitation in the 12 months follow-up period.\n5. 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\n6. Cardiomyopathy in association with a neuromuscular disorder e.g. Duchenne's progressive muscular dystrophy\n7. Previous cardiac surgery\n8. 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\n9. Clinical significant anaemia (haemoglobin \\< 6 mmol/L), leukopenia (leucocytes \\< 2 109/L), leucocytosis (leucocytes \\> 14 109/L) or thrombocytopenia (thrombocytes \\< 50 109/L)\n10. Reduced kidney function (eGFR \\< 30 ml/min)\n11. Left ventricular thrombus\n12. Anticoagulation treatment that cannot be paused during cell injections.\n13. Patients with reduced immune response\n14. History with malignant disease within five years of inclusion or suspected malignity - except treated skin cancer other than melanoma\n15. Pregnant women\n16. Woman of childbearing potential unless βHCG negative and they should be on contraception during the trial\n17. Other experimental treatment within four weeks of baseline tests\n18. Participation in another intervention trial\n19. Life expectancy less than one year"}, 'identificationModule': {'nctId': 'NCT03797092', 'briefTitle': 'Stem Cell Therapy in Non-IschEmic Non-treatable Dilated CardiomyopathiEs II: a Pilot Study', 'organization': {'class': 'OTHER', 'fullName': 'Rigshospitalet, Denmark'}, 'officialTitle': 'Stem Cell Therapy in Non-IschEmic Non-treatable Dilated CardiomyopathiEs II: a Pilot Study', 'orgStudyIdInfo': {'id': 'SCIENCE II - Pilot'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Active', 'description': 'Allogeneic adipose-derived stromal cells (CSCC\\_ASC)', 'interventionNames': ['Biological: Allogeneic adipose-derived stromal cells (CSCC_ASC)', 'Other: Control group']}, {'type': 'NO_INTERVENTION', 'label': 'Control group', 'description': 'No treatment'}], 'interventions': [{'name': 'Allogeneic adipose-derived stromal cells (CSCC_ASC)', 'type': 'BIOLOGICAL', 'otherNames': ['Investigational medicinal product'], 'description': 'Active group', 'armGroupLabels': ['Active']}, {'name': 'Control group', 'type': 'OTHER', 'description': 'No treatment', 'armGroupLabels': ['Active']}]}, 'contactsLocationsModule': {'locations': [{'zip': '2100', 'city': 'Copenhagen', 'status': 'RECRUITING', 'country': 'Denmark', 'contacts': [{'name': 'Jens Kastrup, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'The Heart Centre, Rigshospitalet University Hospital Copenhagen,', 'geoPoint': {'lat': 55.67594, 'lon': 12.56553}}], 'centralContacts': [{'name': 'Jens Kastrup, MD, DMSc', 'role': 'CONTACT', 'email': 'jens.akstrup@regionh.dk', 'phone': '004535452819'}, {'name': 'Abbas A Qayyum, MD, PhD', 'role': 'CONTACT', 'email': 'abbas.ali.qayyum@regionh.dk', 'phone': '004535451076'}], 'overallOfficials': [{'name': 'Bojan Vrtovec, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Dep. of Cardiology, Uni. Medical Center Ljubljana, Slovenia'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'The entire study will be published and shared with other researchers'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'JKastrup', 'class': 'OTHER'}, 'collaborators': [{'name': 'University Medical Centre Ljubljana', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Professor, Doctor', 'investigatorFullName': 'JKastrup', 'investigatorAffiliation': 'Rigshospitalet, Denmark'}}}}