In Vivo Tracking of USPIO Labeled MSC in the Heart (USPIO-MSC)

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

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.

Study Overview

• Status: Completed
• Conditions: Ischemic Heart Disease
• Intervention / Treatment: Combination product: USPIO labeled MSC injection

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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
Experimental: USPIO labeled MSC injection	Combination product: USPIO labeled MSC injection; USPIO labeled MSC injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
Cardiac pump function changes	Left ventricular ejection fraction, systolic and diastolic volumes after 12 weeks	12 weeks
Cardiac pump function changes	Left ventricular ejection fraction, systolic and diastolic volumes after 26 weeks	26 weeks
CCS class	Canadian Cardiovascular Society (CCS) class after 12 weeks	12 weeks
CCS class	Canadian Cardiovascular Society (CCS) class after 26 weeks	26 weeks
Seattle Angina Questionnaire	Seattle Angina Questionnaire after 12 weeks	12 weeks
Seattle Angina Questionnaire	Seattle Angina Questionnaire after 26 weeks	26 weeks
Weekly number of angina attacks	Weekly number of angina attacks after 12 weeks	12 weeks
Weekly number of angina attacks	Weekly number of angina attacks after 26 weeks	26 weeks
Weekly nitroglycerin consumption	Weekly nitroglycerin consumption after 12 weeks	12 weeks
Weekly nitroglycerin consumption	Weekly nitroglycerin consumption after 26 weeks	26 weeks
Adverse events	Adverse events registration	6 months

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Study Director: Jens Kastrup, MD DMSc, The Heart Centre, Rigshospitalet, University of Copenhagen

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2013
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: August 23, 2018
• First Submitted That Met QC Criteria: August 27, 2018
• First Posted (Actual): August 29, 2018

Study Record Updates

• Last Update Posted (Actual): August 29, 2018
• Last Update Submitted That Met QC Criteria: August 27, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia
• Other Study ID Numbers: USPIO-MSC1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No