Cardiac Progenitor Cell Infusion to Treat Univentricular Heart Disease (PERSEUS)

• ClinicalTrials.gov Identifier: NCT01829750
• Recruitment Status: Completed
• First Posted: April 11, 2013
• Last Update Posted: January 5, 2017
• Sponsor: Okayama University
• Collaborator: Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
• Information provided by (Responsible Party): Hidemasa Oh, Okayama University

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.

Condition or disease	Intervention/treatment	Phase
Hypoplastic Left Heart Syndrome; Single Right Ventricle; Single Left Ventricle	Genetic: Cardiac progenitor cell infusion	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of Intracoronary Infusion of Cardiac Progenitor Cells in Patients With Univentricular Heart Disease
• Study Start Date: April 2013
• Actual Primary Completion Date: March 2016
• Actual Study Completion Date: September 2016

Arms and Interventions

Arm	Intervention/treatment
Sham Comparator: Control; (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.	Genetic: Cardiac progenitor cell infusion; (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.
Active Comparator: Cardiac progenitor cell infusion; (Stage 1) single dose, intracoronary infusion of 0.3 million cells/kg cardiac progenitor cells	Genetic: Cardiac progenitor cell infusion; (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.

Outcome Measures

Primary Outcome Measures :

1. Cardiac function [ Time Frame: 3 Months ]
   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 :

1. Cardiac function [ Time Frame: 12 Months ]
   The secondary outcome measure is to determine the cardiac function improvements by three different imaging modalities at 12 months after treatment.

Other Outcome Measures:

1. Clinical symptoms [ Time Frame: 3 and 12 Months ]
   Clinical symptoms and BNP levels will be assessed at 3- and 12-months after treatment and compared with control group.

Eligibility Criteria

• Ages Eligible for Study: up to 20 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age: Age is 0 year or more and 20 years or less at the time of enrollment.
2. The patients have functional single ventricular physiology with the indication to have stage-2 or -3 palliative surgeries.
3. The ventricular ejection fraction <60%.

Exclusion Criteria:

1. Cardiogenic shock
2. A patient with unstoppable extracorporeal circulation
3. A patient with lethal, uncontrollable arrhythmia
4. A patient with a complication of coronary artery disease
5. A patient with a complication of brain dysfunction due to circulatory failure
6. A patient with malignant neoplasm
7. A patient with a complication of serious neurologic disorder
8. A patient with high-grade pulmonary embolism or pulmonary hypertension
9. A patient with high-grade renal failure
10. A patient with multiple organ failure
11. Active infection (including endocarditis)
12. Sepsis
13. Active hemorrhagic disease (e. g. gastrointestinal bleeding, injury)

Contacts and Locations

Locations

Japan

Okayama University

Okayama, Japan, 700-8558

Sponsors and Collaborators

Okayama University

Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan

Investigators

• Principal Investigator: Hidemasa Oh, M.D., Ph.D.; Okayama University

More Information

Additional Information:

Center for Innovative Clinical Medicine 

Publications:

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. Epub 2003 Oct 6.

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. Epub 2006 Nov 27.

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.

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. Review.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Hidemasa Oh, Professor, Okayama University
• ClinicalTrials.gov Identifier: NCT01829750
• Other Study ID Numbers: 0329-18; MHLW25040101 ( Other Grant/Funding Number: MHLW25040101 )
• First Posted: April 11, 2013
• Last Update Posted: January 5, 2017
• Last Verified: January 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Hidemasa Oh, Okayama University:

Univentricular heart

Additional relevant MeSH terms:

Heart Diseases; Hypoplastic Left Heart Syndrome; Cardiovascular Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities