Transcoronary Infusion of Cardiac Progenitor Cells in Patients With Single Ventricle Physiology (TICAP)

• ClinicalTrials.gov Identifier: NCT01273857
• Recruitment Status: Completed
• First Posted: January 11, 2011
• Results First Posted: June 15, 2015
• Last Update Posted: November 26, 2021
• Sponsor: Okayama University
• Collaborator: National Cerebral and Cardiovascular Center
• Information provided by (Responsible Party): Hidemasa Oh, MD, Okayama University

Study Description

Brief Summary:

Hypoplastic left heart syndrome (HLHS) and related anomalies involved a single ventricle are characterized by hypoplasia of the left heart and the aorta with compromised systemic cardiac output. Infants with the syndrome generally undergo a staged surgical approach in view of an ultimate Fontan procedure. Although long-term survival in patients with HLHS and related single ventricle physiology has improved markedly with advances in medical and surgical therapies, a growing number of infants will ultimately require heart transplantation for end-stage heart failure due to several potential disadvantages include a negative effect on right ventricular function, arrhythmia, additional volume load via regurgitation from the nonvalved shunt, and impaired growth of the pulmonary artery.

Risk factors for poor outcome of heart transplantation with HLHS and single ventricle physiology are older age at transplantation and previous Fontan operation. New strategies are needed to improve the underlying transplant risks proper for the Fontan failure patients.

Emerging evidence suggests that heart-derived stem/progenitor cells can be used to improved cardiac function in patients with ischemic heart disease. In this trial, the investigators aimed to test the safety and feasibility of intracoronary injection of autologous cardiac progenitor cells in patients with HLHS and related single ventricle anomalies and that could improve ventricular function at 3 months' follow up.

Condition or disease	Intervention/treatment	Phase
Hypoplastic Left Heart Syndrome; Single Ventricle; Heart Failure	Procedure: Autologous cardiac progenitor cell transplantation; Procedure: staged shunt procedure	Phase 1

Detailed Description:

Autologous cardiac progenitor cells are isolated from patients' own cardiac tissues obtained during palliative shunt procedure. Patients will receive 0.3 million/kg of autologous cardiac progenitor cells via intracoronary delivery 1 month after cardiac surgery. Follow-up visits 3 months to 1 year after cell injection will need to prospectively verify the clinical, laboratory, and safety-related data.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Study of Cardiac Progenitor Cell Therapy in Patients With Single Ventricle Physiology
• Study Start Date: January 2011
• Actual Primary Completion Date: January 2013
• Actual Study Completion Date: January 2013

Arms and Interventions

Arm	Intervention/treatment
Sham Comparator: Control; Subjects will undergo standard staged-procedures without cell infusion	Procedure: staged shunt procedure; Norwood-Glenn, Glenn, or Fontan procedure will be applied
Experimental: Cell infusion; Subjects will receive transcoronary infusion of autologous cardiosphere-derived cells 1 month after staged shunt procedure	Procedure: Autologous cardiac progenitor cell transplantation; Patients will receive 0.3 million / kg of autologous cardiac progenitor cells via intracoronary delivery 1 month after cardiac surgery. Follow-up visits 3 months to 1 year after cell injection will need to prospectively verify the clinical, laboratory, and safety-related data.; Other Name: Cardiosphere-derived cells; Procedure: staged shunt procedure; Norwood-Glenn, Glenn, or Fontan procedure will be applied

Outcome Measures

Primary Outcome Measures :

1. Feasibility Evaluation and Major Cardiac Adverse Events Related to Transcoronary Infusion of Cardiac Progenitor Cells [ Time Frame: 3 months to 1 year after cell transplantation ]

   Feasibility was assessed by number of participants discontinued the study due to adverse events or number of participants received unsuccessful cell delivery by study physician. Unsuccessful was defined as failure of coronary selection of guiding catheter or direct cell infusion.

   The primary end point is to monitor major adverse cardiac events include death, sustained/symptomatic ventricular tachycardia, aggravation of heart failure, new myocardial infarction, unplanned cardiovascular operation for cardiac tamponade and infection in the first month after injection, and serially afterwards.

Secondary Outcome Measures :

1. Serious Adverse Events [ Time Frame: 3 months to 1 year after cell transplantation ]
   The incidence of hospitalization for heart failure, ventricular arrhythmia, general infection, and renal and hepatic dysfunction by CDC treatment.

Eligibility Criteria

• Ages Eligible for Study: up to 6 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Infants with hypoplastic left heart syndrome and related single ventricle anomalies undergoing first to third palliative shunt surgeries will be recruited into the study.
• Patients between 0 and 6 years of age are eligible if written informed consent can be obtained.

Exclusion Criteria:

• Cardiogenic shock
• Eisenmenger syndrome
• Uncontrollable arrhythmia
• Severe chronic diseases
• Infections
• Cancer
• Unwillingness to participate

Contacts and Locations

Locations

Japan

Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital

Okayama, Japan, 700-8558

Sponsors and Collaborators

Okayama University

National Cerebral and Cardiovascular Center

Investigators

• Principal Investigator: Hidemasa Oh, M.D., Ph.D.; Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital

More Information

Additional Information:

Center for Innovative Clinical Medicine 

Publications of Results:

Ishigami S, Ohtsuki S, Tarui S, Ousaka D, Eitoku T, Kondo M, Okuyama M, Kobayashi J, Baba K, Arai S, Kawabata T, Yoshizumi K, Tateishi A, Kuroko Y, Iwasaki T, Sato S, Kasahara S, Sano S, Oh H. Intracoronary autologous cardiac progenitor cell transfer in patients with hypoplastic left heart syndrome: the TICAP prospective phase 1 controlled trial. Circ Res. 2015 Feb 13;116(4):653-64. doi: 10.1161/CIRCRESAHA.116.304671. Epub 2014 Nov 17.

Other Publications:

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.

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.

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.

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.

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.

Tarui S, Ishigami S, Ousaka D, Kasahara S, Ohtsuki S, Sano S, Oh H. Transcoronary infusion of cardiac progenitor cells in hypoplastic left heart syndrome: Three-year follow-up of the Transcoronary Infusion of Cardiac Progenitor Cells in Patients With Single-Ventricle Physiology (TICAP) trial. J Thorac Cardiovasc Surg. 2015 Nov;150(5):1198-1207, 1208.e1-2. doi: 10.1016/j.jtcvs.2015.06.076. Epub 2015 Jul 8.

• Responsible Party: Hidemasa Oh, MD, MD., Ph.D., Okayama University
• ClinicalTrials.gov Identifier: NCT01273857
• Other Study ID Numbers: MHLW10103228
• First Posted: January 11, 2011
• Results First Posted: June 15, 2015
• Last Update Posted: November 26, 2021
• Last Verified: November 2021

Keywords provided by Hidemasa Oh, MD, Okayama University:

Cardiac progenitor cells; Cell therapy; Hypoplastic Left Heart Syndrome; Single Ventricle; Norwood; Sano modification; Glenn; Fontan

Additional relevant MeSH terms:

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