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

Heart Failure Clinical Trial

— TICAP  

Official title:

Phase I Study of Cardiac Progenitor Cell Therapy in Patients With Single Ventricle Physiology

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01273857
• Other study ID #: MHLW10103228
• Status: Completed
• Phase: Phase 1
• Start date: January 2011
• Est. completion date: January 2013

Study information

• Verified date: November 2021
• Source: Okayama University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 6 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Hypoplastic Left Heart Syndrome
• Single Ventricle
• Univentricular Heart

Intervention

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.
• staged shunt procedure
Norwood-Glenn, Glenn, or Fontan procedure will be applied

Locations

Country	Name	City	State
Japan	Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital	Okayama

Sponsors (2)

Lead Sponsor	Collaborator
Okayama University	National Cerebral and Cardiovascular Center

Country where clinical trial is conducted

Japan, 

References & Publications (5)

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 p — View 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. — View 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. Epub 2006 Nov 27. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility Evaluation and Major Cardiac Adverse Events Related to Transcoronary Infusion of Cardiac Progenitor Cells	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.	3 months to 1 year after cell transplantation
Secondary	Serious Adverse Events	The incidence of hospitalization for heart failure, ventricular arrhythmia, general infection, and renal and hepatic dysfunction by CDC treatment.	3 months to 1 year after cell transplantation

External Links

•   Center for Innovative Clinical Medicine