In Vivo Tracking of USPIO Labeled MSC in the Heart

Ischemic Heart Disease Clinical Trial

— USPIO-MSC  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03651791
• Other study ID #: USPIO-MSC1
• Status: Completed
• Phase: Phase 1
• Start date: May 2013
• Est. completion date: October 2017

Study information

• Verified date: August 2018
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: October 2017
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Heart Diseases
• Ischemia
• Ischemic Heart Disease
• Myocardial Ischemia

Intervention

Combination Product:
• USPIO labeled MSC injection
USPIO labeled MSC injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MSC identification using MRI in-vivo on day 0	Being able to identify the iron-oxide labeled mesenchymal stromal cells on day 0 after injection into the myocardium by MRI.	24 hours
Secondary	MSC identification using MRI in-vivo on day 1	Being able to identify the iron-oxide labeled mesenchymal stromal cells on day 1	1 day
Secondary	MSC identification using MRI in-vivo on day 7	Being able to identify the iron-oxide labeled mesenchymal stromal cells on day 7	7 days
Secondary	MSC identification using MRI in-vivo after 2 weeks	Being able to identify the iron-oxide labeled mesenchymal stromal cells after 2 weeks	2 weeks
Secondary	MSC identification using MRI in-vivo after 4 weeks	Being able to identify the iron-oxide labeled mesenchymal stromal cells after 4 weeks	4 weeks
Secondary	MSC identification using MRI in-vivo after 8 weeks	Being able to identify the iron-oxide labeled mesenchymal stromal cells after 8 weeks	8 weeks
Secondary	MSC identification using MRI in-vivo after 12 weeks	Being able to identify the iron-oxide labeled mesenchymal stromal cells after 12 weeks	12 weeks
Secondary	MSC identification using MRI in-vivo after 26 weeks	Being able to identify the iron-oxide labeled mesenchymal stromal cells after 26 weeks	26 weeks
Secondary	Cardiac pump function changes	Left ventricular ejection fraction, systolic and diastolic volumes after 12 weeks	12 weeks
Secondary	Cardiac pump function changes	Left ventricular ejection fraction, systolic and diastolic volumes after 26 weeks	26 weeks
Secondary	CCS class	Canadian Cardiovascular Society (CCS) class after 12 weeks	12 weeks
Secondary	CCS class	Canadian Cardiovascular Society (CCS) class after 26 weeks	26 weeks
Secondary	Seattle Angina Questionnaire	Seattle Angina Questionnaire after 12 weeks	12 weeks
Secondary	Seattle Angina Questionnaire	Seattle Angina Questionnaire after 26 weeks	26 weeks
Secondary	Weekly number of angina attacks	Weekly number of angina attacks after 12 weeks	12 weeks
Secondary	Weekly number of angina attacks	Weekly number of angina attacks after 26 weeks	26 weeks
Secondary	Weekly nitroglycerin consumption	Weekly nitroglycerin consumption after 12 weeks	12 weeks
Secondary	Weekly nitroglycerin consumption	Weekly nitroglycerin consumption after 26 weeks	26 weeks
Secondary	Adverse events	Adverse events registration	6 months