NCT01273857

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
14

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jan 2011

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2011

Completed
9 days until next milestone

First Submitted

Initial submission to the registry

January 10, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 11, 2011

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2013

Completed
2.5 years until next milestone

Results Posted

Study results publicly available

June 15, 2015

Completed
Last Updated

November 26, 2021

Status Verified

November 1, 2021

Enrollment Period

2 years

First QC Date

January 10, 2011

Results QC Date

April 21, 2015

Last Update Submit

November 23, 2021

Conditions

Hypoplastic Left Heart SyndromeSingle VentricleHeart Failure

Keywords

Cardiac progenitor cellsCell therapyHypoplastic Left Heart SyndromeSingle VentricleNorwoodSano modificationGlennFontan

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (1)

  • Serious Adverse Events

    3 months to 1 year after cell transplantation

Study Arms (2)

Control

SHAM COMPARATOR

Subjects will undergo standard staged-procedures without cell infusion

Procedure: staged shunt procedure

Cell infusion

EXPERIMENTAL

Subjects will receive transcoronary infusion of autologous cardiosphere-derived cells 1 month after staged shunt procedure

Procedure: Autologous cardiac progenitor cell transplantationProcedure: staged shunt procedure

Interventions

Autologous cardiac progenitor cell transplantationPROCEDURE

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.

Also known as: Cardiosphere-derived cells
Cell infusion
staged shunt procedurePROCEDURE

Norwood-Glenn, Glenn, or Fontan procedure will be applied

Cell infusionControl

Eligibility Criteria

AgeUp to 6 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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.

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

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

Okayama, 700-8558, Japan

Location

Related Publications (8)

  • 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.

    PMID: 19038683BACKGROUND

  • 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.

    PMID: 18754813BACKGROUND

  • 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.

    PMID: 17502484BACKGROUND

  • 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.

    PMID: 17150190BACKGROUND

  • 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.

    PMID: 25403163RESULT

  • Hirai K, Sawada R, Hayashi T, Araki T, Nakagawa N, Kondo M, Yasuda K, Hirata T, Sato T, Nakatsuka Y, Yoshida M, Kasahara S, Baba K, Oh H; TICAP/PERSEUS Study Group. Eight-Year Outcomes of Cardiosphere-Derived Cells in Single Ventricle Congenital Heart Disease. J Am Heart Assoc. 2024 Nov 19;13(22):e038137. doi: 10.1161/JAHA.124.038137. Epub 2024 Nov 11.

    PMID: 39526355DERIVED

  • 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.

    PMID: 29367212DERIVED

  • 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.

    PMID: 26232942DERIVED

MeSH Terms

Conditions

Hypoplastic Left Heart SyndromeUniventricular HeartHeart Failure

Condition Hierarchy (Ancestors)

Heart Defects, CongenitalCardiovascular AbnormalitiesCardiovascular DiseasesHeart DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

Title
Prof. Hidemasa Oh
Organization
Okayama University Hospital
hidemasa@md.okayama-u.ac.jp
+81-086-235-6506

Study Officials

  • Hidemasa Oh, M.D., Ph.D.

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

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD., Ph.D.

Study Record Dates

First Submitted

January 10, 2011

First Posted

January 11, 2011

Study Start

January 1, 2011

Primary Completion

January 1, 2013

Study Completion

January 1, 2013

Last Updated

November 26, 2021

Results First Posted

June 15, 2015

Record last verified: 2021-11

Locations

JP(1)