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Phase I Safety and Feasibility Study of Intracoronary Delivery of Autologous Bone Marrow Derived Mononuclear Cells

Primary Purpose

Congenital Heart Disease

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Autologous Bone Marrow-derived Mononuclear Cells

About this trial

This is an interventional treatment trial for Congenital Heart Disease focused on measuring Single right ventricular failure

Eligibility Criteria

2 Years - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Individuals with Fontan circulation with right ventricular dysfunction
Ejection fraction equal to or less than 40% despite optimal outpatient medical management for at least 3 months
Able to undergo bone marrow aspirate according to clinical consultation with hematology (INR must be maintained at or below 1.5)
Able to undergo an MRI or CT examination

Exclusion Criteria:

Individuals or parents of minors unwilling to consent to participation
Individuals with severe chronic diseases, extra-cardiac syndromes, or cancer
Females 10 years and older with positive pregnancy test or lack of effective birth control method
Individuals currently requiring IV inotropes
Individuals with bleeding disorders or history of thrombosis
Individuals not eligible for MRI and have elevated serum creatinine level (eGFR less that 45 mL/min) and therefore cannot have a CT examination
Individuals not eligible for MRI and have a prior significant reaction to intravenous contrast required for CT examination
Individuals with the following conditions within 60 days prior to procedure:
- Cardiogenic shock or extracorporeal circulation;
- New arrhythmia that required medication for control;
- Documented infection requiring treatment with antibiotics, and/or current infection being treated with antibiotics;
- Cardiac condition requiring emergency procedure;
- Cardiovascular surgery;
- Seizures or history of significant neurological injury;
- Multi-system organ failure including acute or chronic renal failure

Sites / Locations

Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single-arm

Arm Description

Intracoronary delivery of autologous bone marrow-derived mononuclear cells using catheterization procedure

Outcomes

Primary Outcome Measures

Number of related serious adverse events

Secondary Outcome Measures

Number of subjects who died

Number of subjects with sustained or symptomatic ventricular arrhythmias

Number of subjects with acute decompensated heart failure

Number of subjects with myocardial infarction

Number of subjects with cardiac infection

Number of subjects with unexpected cardiovascular procedures within 6 months following cellular transplantation

Percentage of subjects that have cells delivered

Percentage of subjects completing the 6-month follow-up

Change in CT/MRI derived right ventricle ejection fraction

Change in diastolic ventricular volume

Change in systolic ventricular volume

Change in echocardiography derived right ventricle ejection fraction

Full Information

NCT ID

NCT02549625

First Posted

September 10, 2015

Last Updated

May 12, 2021

Sponsor

Timothy J Nelson, MD, PhD

Collaborators

Mayo Clinic

1. Study Identification

Unique Protocol Identification Number

NCT02549625

Brief Title

Phase I Safety and Feasibility Study of Intracoronary Delivery of Autologous Bone Marrow Derived Mononuclear Cells

Official Title

Phase I Safety and Feasibility Study of Intracoronary Delivery of Autologous Bone Marrow Derived Mononuclear Cells for Systemic, Single Right Ventricular Failure Due to Congenital Heart Disease

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Completed

Study Start Date

August 2015 (undefined)

Primary Completion Date

November 2020 (Actual)

Study Completion Date

November 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Timothy J Nelson, MD, PhD

Collaborators

Mayo Clinic

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The objective of this study is to determine the safety and feasibility of autologous mononuclear cells (MNC) collected from bone marrow (BM) and intracoronary delivery for individuals with declining performance of their single right ventricle systemic pumps. This procedure has the potential to foster a new strategy for congenital heart patients. This is an open-label study of autologous MNC derived from bone marrow with a 2-year follow-up to document 1) related serious adverse events and 2) monitor changes in cardiac structure and function.

Detailed Description

This study is an open label Phase I trial to determine the safety and feasibility of bone marrow-derived mononuclear cells delivered into the coronary circulation of subjects with Fontan circulation and right ventricular dysfunction. Subjects will be screened at outpatient clinic visits at Mayo Clinic and interested qualified subjects will be consented and offered participation in this trial. Once informed consent has been obtained; preoperative values will be established and a selection committee will review subjects within three days prior to planned procedure to confirm inclusion and exclusion criteria. This will require a non-study cardiologist to review the clinical case and confirm the baseline cardiac function with evidence of disease progression with right ventricle dysfunction. However, individuals with decreased cardiac function requiring inotropic support and immediate listing for cardiac transplantation will NOT be included such that the risk of this research procedure may not be acceptable. Following cell-based product delivery, subjects will be followed for 6-months according to a pre-determined schedule that includes imaging studies along with questionnaires, electrophysiology and laboratory studies. Subjects will be contacted for an additional 18-months for surveillance by phone.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Congenital Heart Disease

Keywords

Single right ventricular failure

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Single-arm

Arm Type

Experimental

Arm Description

Intracoronary delivery of autologous bone marrow-derived mononuclear cells using catheterization procedure

Intervention Type

Biological

Intervention Name(s)

Autologous Bone Marrow-derived Mononuclear Cells

Other Intervention Name(s)

MNC

Primary Outcome Measure Information:

Title

Number of related serious adverse events

Time Frame

6 months post cell delivery

Secondary Outcome Measure Information:

Title

Number of subjects who died

Time Frame

6 months post cell delivery

Title

Number of subjects with sustained or symptomatic ventricular arrhythmias

Time Frame

6 months post cell delivery

Title

Number of subjects with acute decompensated heart failure

Time Frame

6 months post cell delivery

Title

Number of subjects with myocardial infarction

Time Frame

6 months post cell delivery

Title

Number of subjects with cardiac infection

Time Frame

6 months post cell delivery

Title

Number of subjects with unexpected cardiovascular procedures within 6 months following cellular transplantation

Time Frame

6 months post cell delivery

Title

Percentage of subjects that have cells delivered

Time Frame

6 months post cell delivery

Title

Percentage of subjects completing the 6-month follow-up

Time Frame

6 months post cell delivery

Title

Change in CT/MRI derived right ventricle ejection fraction

Time Frame

Baseline, 6 months post cell delivery

Title

Change in diastolic ventricular volume

Time Frame

Baseline, 6 months post cell delivery

Title

Change in systolic ventricular volume

Time Frame

Baseline, 6 months post cell delivery

Title

Change in echocardiography derived right ventricle ejection fraction

Time Frame

Baseline, 6 months post cell delivery

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

30 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Individuals with Fontan circulation with right ventricular dysfunction Ejection fraction equal to or less than 40% despite optimal outpatient medical management for at least 3 months Able to undergo bone marrow aspirate according to clinical consultation with hematology (INR must be maintained at or below 1.5) Able to undergo an MRI or CT examination Exclusion Criteria: Individuals or parents of minors unwilling to consent to participation Individuals with severe chronic diseases, extra-cardiac syndromes, or cancer Females 10 years and older with positive pregnancy test or lack of effective birth control method Individuals currently requiring IV inotropes Individuals with bleeding disorders or history of thrombosis Individuals not eligible for MRI and have elevated serum creatinine level (eGFR less that 45 mL/min) and therefore cannot have a CT examination Individuals not eligible for MRI and have a prior significant reaction to intravenous contrast required for CT examination Individuals with the following conditions within 60 days prior to procedure: Cardiogenic shock or extracorporeal circulation; New arrhythmia that required medication for control; Documented infection requiring treatment with antibiotics, and/or current infection being treated with antibiotics; Cardiac condition requiring emergency procedure; Cardiovascular surgery; Seizures or history of significant neurological injury; Multi-system organ failure including acute or chronic renal failure

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Timothy J Nelson, M.D., Ph.D.

Organizational Affiliation

Mayo Clinic

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Muhammad Y Qureshi, MBBS

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Links:

URL

https://www.mayo.edu/research/clinical-trials

Description

Mayo Clinic Clinical Trials

Learn more about this trial

Phase I Safety and Feasibility Study of Intracoronary Delivery of Autologous Bone Marrow Derived Mononuclear Cells

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