Clinical trial NCT03651791: In Vivo Tracking of USPIO Labeled MSC in the Heart
Official title: In Vivo MRI Tracking of Mesenchymal Stromal Cells Labeled With Ultra-Small Paramagnetic Iron Oxide Particles After Intramyocardial Transplantation in Patients With Chronic Ischemic Heart Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ischemic Heart Disease
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2018-08-29
Enrollment: 5
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the ability to trace iron oxide-labeled mesenchymal stromal cells with magnetic resonance imaging (MRI) after NOGA-guided injection therapy into the myocardium in patients with ischemic heart disease.

Detailed description: Aims:

To evaluate the ability to trace iron oxide-labeled mesenchymal stromal cells with magnetic resonance imaging (MRI) after NOGA-guided injection therapy into the myocardium.

To evaluate the safety and efficacy of treatment with iron oxide-labeled mesenchymal stromal cells to form new heart muscle cells and blood vessels in the myocardium submitted by NOGA-guided injection therapy in the myocardium in order to improve myocardial blood flow and reduce patients' symptoms.

Patient Population:

Patients with coronary artery disease not treatable with additional bypass surgery or percutaneous coronary intervention who have angina pectoris (Canadian Cardiovascular Society (CCS) class II-III) or angina equivalent shortness of breath (New York Heart Association (NYHA) class II -III).

Study Design A prospective, non-randomized, pilot study including 5-10 patients. Patients will by means of the percutaneous NOGA injection catheter system receive 12-15 intramyocardial injections. The number depending on the amount of cultured cells and distributed uniformly in the peripheral zone of a presumed ischemic area in the left ventricle demonstrated by angiography, magnetic resonance imaging and NOGA mapping.

Eligibility criteria: Inclusion Criteria:

* Age between 30 and 80 years.
* Signed informed consent.
* Chronic stable ischemic heart disease
* New York Heart Association (NYHA) class II-IV or Canadian Cardiovascular Society (CCS) class II-IV
* Maximal tolerable angina and/or heart failure medication.
* Angiography within 12 months of inclusion. Angiography must have at least one larger coronary vessel with a significant stenosis with no option for revascularization (Angiographies evaluated by an independent thoracic surgeon and an interventional cardiologist).
* Patients who have had revascularization done within 6 months of inclusion must have a new angiography at least 4 months after the intervention to rule out early restenosis.

Exclusion Criteria:

* Pregnant or fertile women.
* Clinical significant anemia, leukopenia, leukocytosis or thrombocythemia.
* Diminished functional capacity for other reasons such as: chronic obstructive pulmonary disease (COLD) with Forced Expiratory Volume in 1 second (FEV1)\<1 L/min, moderate to severe claudication or morbid obesity.
* Patients with reduced immune response or treated with immunosuppressive medication.
* Moderate to severe valvular disease or valvular disease with option for valvular surgery.
* Acute coronary syndrome with elevation of coronary markers, stroke or Transitory Cerebral Ischemia (TCI) within 6 weeks of inclusion.
* History with malignant disease within 5 years of inclusion or suspected malignity.
* Other experimental treatment within 4 weeks of baseline evaluation.
* Other revascularization treatment within 4 months of treatment.
* Contraindications for Magnetic Resonance Imaging (MRI) such as: Claustrophobia, pacemaker, Implantable Cardioverter Defibrillator (ICD) unit, metal fragments or metal implants in the cranium

Primary outcomes:
measure: MSC identification using MRI in-vivo on day 0
timeFrame: 24 hours
Secondary outcomes:
measure: MSC identification using MRI in-vivo on day 1
timeFrame: 1 day
measure: MSC identification using MRI in-vivo on day 7
timeFrame: 7 days
measure: MSC identification using MRI in-vivo after 2 weeks
timeFrame: 2 weeks
measure: MSC identification using MRI in-vivo after 4 weeks
timeFrame: 4 weeks
measure: MSC identification using MRI in-vivo after 8 weeks
timeFrame: 8 weeks
measure: MSC identification using MRI in-vivo after 12 weeks
timeFrame: 12 weeks
measure: MSC identification using MRI in-vivo after 26 weeks
timeFrame: 26 weeks
measure: Cardiac pump function changes
timeFrame: 12 weeks
measure: Cardiac pump function changes
timeFrame: 26 weeks
measure: CCS class
timeFrame: 12 weeks
measure: CCS class
timeFrame: 26 weeks
measure: Seattle Angina Questionnaire
timeFrame: 12 weeks
measure: Seattle Angina Questionnaire
timeFrame: 26 weeks
measure: Weekly number of angina attacks
timeFrame: 12 weeks
measure: Weekly number of angina attacks
timeFrame: 26 weeks
measure: Weekly nitroglycerin consumption
timeFrame: 12 weeks
measure: Weekly nitroglycerin consumption
timeFrame: 26 weeks
measure: Adverse events
timeFrame: 6 months
Other outcomes:
Locations:
Study officials:
affiliation: The Heart Centre, Rigshospitalet, University of Copenhagen
name: Jens Kastrup, MD DMSc
role: STUDY_DIRECTOR
References:
citation: Mathiasen AB, Hansen L, Friis T, Thomsen C, Bhakoo K, Kastrup J. Optimal labeling dose, labeling time, and magnetic resonance imaging detection limits of ultrasmall superparamagnetic iron-oxide nanoparticle labeled mesenchymal stromal cells. Stem Cells Int. 2013;2013:353105. doi: 10.1155/2013/353105. Epub 2013 Mar 19.
citation: Hansen L, Hansen AB, Mathiasen AB, Ng M, Bhakoo K, Ekblond A, Kastrup J, Friis T. Ultrastructural characterization of mesenchymal stromal cells labeled with ultrasmall superparamagnetic iron-oxide nanoparticles for clinical tracking studies. Scand J Clin Lab Invest. 2014 Aug;74(5):437-46. doi: 10.3109/00365513.2014.900698. Epub 2014 Apr 15.
citation: Mathiasen AB, Qayyum AA, Jorgensen E, Helqvist S, Ekblond A, Ng M, Bhakoo K, Kastrup J. In Vivo MRI Tracking of Mesenchymal Stromal Cells Labeled with Ultrasmall Paramagnetic Iron Oxide Particles after Intramyocardial Transplantation in Patients with Chronic Ischemic Heart Disease. Stem Cells Int. 2019 Nov 14;2019:2754927. doi: 10.1155/2019/2754927. eCollection 2019.