Cardiac Progenitor Cell Infusion to Treat Univentricular Heart Disease (PERSEUS)
Primary Purpose
Hypoplastic Left Heart Syndrome, Single Right Ventricle, Single Left Ventricle
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Cardiac progenitor cell infusion
Sponsored by
About this trial
This is an interventional treatment trial for Hypoplastic Left Heart Syndrome focused on measuring Univentricular heart
Eligibility Criteria
Inclusion Criteria:
- Age: Age is 0 year or more and 20 years or less at the time of enrollment.
- The patients have functional single ventricular physiology with the indication to have stage-2 or -3 palliative surgeries.
- The ventricular ejection fraction <60%.
Exclusion Criteria:
- Cardiogenic shock
- A patient with unstoppable extracorporeal circulation
- A patient with lethal, uncontrollable arrhythmia
- A patient with a complication of coronary artery disease
- A patient with a complication of brain dysfunction due to circulatory failure
- A patient with malignant neoplasm
- A patient with a complication of serious neurologic disorder
- A patient with high-grade pulmonary embolism or pulmonary hypertension
- A patient with high-grade renal failure
- A patient with multiple organ failure
- Active infection (including endocarditis)
- Sepsis
- Active hemorrhagic disease (e. g. gastrointestinal bleeding, injury)
Sites / Locations
- Okayama University
Arms of the Study
Arm 1
Arm 2
Arm Type
Sham Comparator
Active Comparator
Arm Label
Control
Cardiac progenitor cell infusion
Arm Description
(Stage 1) No active intervention after standard surgical treatment (Stage 2) Rescuing transplantation by cardiac progenitor cell infusion is applicable in patients, along with their written consent, 4 months after palliations who were assigned as control group in stage 1.
(Stage 1) single dose, intracoronary infusion of 0.3 million cells/kg cardiac progenitor cells
Outcomes
Primary Outcome Measures
Cardiac function
The primary outcome measure is to evaluate the cardiac function improvement by echocardiography, ventriculography, and cardiac MRI, which are conducted before and 3 months after surgical treatment.
Secondary Outcome Measures
Cardiac function
The secondary outcome measure is to determine the cardiac function improvements by three different imaging modalities at 12 months after treatment.
Full Information
NCT ID
NCT01829750
First Posted
April 9, 2013
Last Updated
November 23, 2021
Sponsor
Okayama University
Collaborators
Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
1. Study Identification
Unique Protocol Identification Number
NCT01829750
Brief Title
Cardiac Progenitor Cell Infusion to Treat Univentricular Heart Disease (PERSEUS)
Official Title
Phase 2 Study of Intracoronary Infusion of Cardiac Progenitor Cells in Patients With Univentricular Heart Disease
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
April 2013 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
September 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Okayama University
Collaborators
Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to investigate the efficacy of intracoronary infusion of cardiac progenitor cells in patients with univentricular heart disease. Patients with preoperative high-risk group or whose cardiac function did not recover postoperatively eventually have no choice other than heart transplantation.
Detailed Description
Following the safety verification of the Phase I study (TICAP trial) that has been implemented and completed, the efficacy will be verified in this Phase II clinical study. The rationale of this study is based on the animal studies that transplanted cardiac progenitor cells may regenerate damaged myocardium by giving rise to cardiac muscle and vascular cell types. Preclinical and phase I studies indicate the possibilities of cardiac function improvements and reduced myocardial fibrosis by progenitor cell infusion.
The efficacy of cell transplantation is assessed as the primary endpoint of the Phase II clinical study. The improvements of cardiac ejection fraction assessed by echocardiography, ventriculography, and cardiac MRI, which are conducted before and after treatment, are assessed as the evaluation items. The absolute values of the improvement of cardiac ejection fraction obtained by the above three imaging modalities before and after treatment are compared between two groups of the transplantation group and non-transplantation group.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypoplastic Left Heart Syndrome, Single Right Ventricle, Single Left Ventricle
Keywords
Univentricular heart
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
Sham Comparator
Arm Description
(Stage 1) No active intervention after standard surgical treatment
(Stage 2) Rescuing transplantation by cardiac progenitor cell infusion is applicable in patients, along with their written consent, 4 months after palliations who were assigned as control group in stage 1.
Arm Title
Cardiac progenitor cell infusion
Arm Type
Active Comparator
Arm Description
(Stage 1) single dose, intracoronary infusion of 0.3 million cells/kg cardiac progenitor cells
Intervention Type
Genetic
Intervention Name(s)
Cardiac progenitor cell infusion
Intervention Description
(Stage 1) Cardiac progenitor cell infusion in patients who assigned as active comparator group
(Stage 2) Rescuing transplantation is applicable in patients, along with their written consent, 4 months after palliations who were allocated as control group in stage 1.
Primary Outcome Measure Information:
Title
Cardiac function
Description
The primary outcome measure is to evaluate the cardiac function improvement by echocardiography, ventriculography, and cardiac MRI, which are conducted before and 3 months after surgical treatment.
Time Frame
3 Months
Secondary Outcome Measure Information:
Title
Cardiac function
Description
The secondary outcome measure is to determine the cardiac function improvements by three different imaging modalities at 12 months after treatment.
Time Frame
12 Months
Other Pre-specified Outcome Measures:
Title
Clinical symptoms
Description
Clinical symptoms and BNP levels will be assessed at 3- and 12-months after treatment and compared with control group.
Time Frame
3 and 12 Months
10. Eligibility
Sex
All
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age: Age is 0 year or more and 20 years or less at the time of enrollment.
The patients have functional single ventricular physiology with the indication to have stage-2 or -3 palliative surgeries.
The ventricular ejection fraction <60%.
Exclusion Criteria:
Cardiogenic shock
A patient with unstoppable extracorporeal circulation
A patient with lethal, uncontrollable arrhythmia
A patient with a complication of coronary artery disease
A patient with a complication of brain dysfunction due to circulatory failure
A patient with malignant neoplasm
A patient with a complication of serious neurologic disorder
A patient with high-grade pulmonary embolism or pulmonary hypertension
A patient with high-grade renal failure
A patient with multiple organ failure
Active infection (including endocarditis)
Sepsis
Active hemorrhagic disease (e. g. gastrointestinal bleeding, injury)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hidemasa Oh, M.D., Ph.D.
Organizational Affiliation
Okayama University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Okayama University
City
Okayama
ZIP/Postal Code
700-8558
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
14530411
Citation
Oh H, Bradfute SB, Gallardo TD, Nakamura T, Gaussin V, Mishina Y, Pocius J, Michael LH, Behringer RR, Garry DJ, Entman ML, Schneider MD. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12313-8. doi: 10.1073/pnas.2132126100. Epub 2003 Oct 6.
Results Reference
background
PubMed Identifier
17150190
Citation
Tateishi K, Ashihara E, Honsho S, Takehara N, Nomura T, Takahashi T, Ueyama T, Yamagishi M, Yaku H, Matsubara H, Oh H. Human cardiac stem cells exhibit mesenchymal features and are maintained through Akt/GSK-3beta signaling. Biochem Biophys Res Commun. 2007 Jan 19;352(3):635-41. doi: 10.1016/j.bbrc.2006.11.096. Epub 2006 Nov 27.
Results Reference
background
PubMed Identifier
17502484
Citation
Tateishi K, Ashihara E, Takehara N, Nomura T, Honsho S, Nakagami T, Morikawa S, Takahashi T, Ueyama T, Matsubara H, Oh H. Clonally amplified cardiac stem cells are regulated by Sca-1 signaling for efficient cardiovascular regeneration. J Cell Sci. 2007 May 15;120(Pt 10):1791-800. doi: 10.1242/jcs.006122.
Results Reference
background
PubMed Identifier
18754813
Citation
Tateishi K, Takehara N, Matsubara H, Oh H. Stemming heart failure with cardiac- or reprogrammed-stem cells. J Cell Mol Med. 2008 Dec;12(6A):2217-32. doi: 10.1111/j.1582-4934.2008.00487.x. Epub 2008 Aug 27.
Results Reference
background
PubMed Identifier
19038683
Citation
Takehara N, Tsutsumi Y, Tateishi K, Ogata T, Tanaka H, Ueyama T, Takahashi T, Takamatsu T, Fukushima M, Komeda M, Yamagishi M, Yaku H, Tabata Y, Matsubara H, Oh H. Controlled delivery of basic fibroblast growth factor promotes human cardiosphere-derived cell engraftment to enhance cardiac repair for chronic myocardial infarction. J Am Coll Cardiol. 2008 Dec 2;52(23):1858-1865. doi: 10.1016/j.jacc.2008.06.052.
Results Reference
background
PubMed Identifier
28052915
Citation
Ishigami S, Ohtsuki S, Eitoku T, Ousaka D, Kondo M, Kurita Y, Hirai K, Fukushima Y, Baba K, Goto T, Horio N, Kobayashi J, Kuroko Y, Kotani Y, Arai S, Iwasaki T, Sato S, Kasahara S, Sano S, Oh H. Intracoronary Cardiac Progenitor Cells in Single Ventricle Physiology: The PERSEUS (Cardiac Progenitor Cell Infusion to Treat Univentricular Heart Disease) Randomized Phase 2 Trial. Circ Res. 2017 Mar 31;120(7):1162-1173. doi: 10.1161/CIRCRESAHA.116.310253. Epub 2017 Jan 4.
Results Reference
result
PubMed Identifier
29367212
Citation
Sano T, Ousaka D, Goto T, Ishigami S, Hirai K, Kasahara S, Ohtsuki S, Sano S, Oh H. Impact of Cardiac Progenitor Cells on Heart Failure and Survival in Single Ventricle Congenital Heart Disease. Circ Res. 2018 Mar 30;122(7):994-1005. doi: 10.1161/CIRCRESAHA.117.312311. Epub 2018 Jan 24.
Results Reference
derived
Links:
URL
http://shin-iryo.hospital.okayama-u.ac.jp/center/index3.html#english
Description
Center for Innovative Clinical Medicine
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Cardiac Progenitor Cell Infusion to Treat Univentricular Heart Disease (PERSEUS)
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