Hypoplastic Left Heart SyndromePhase 1TICAPNCT01273857

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

A Phase 1 study testing Autologous cardiac progenitor cell transplantation and staged shunt procedure in people with Hypoplastic Left Heart Syndrome and Single Ventricle, run by Okayama University at 1 site in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages Up to 6 years
Conditions the study is for: Hypoplastic Left Heart Syndrome, Single Ventricle, Heart Failure
What is being tested?: Autologous cardiac progenitor cell transplantation and staged shunt procedure
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 14 participants
Where: 1 siteJapan
Study dates: Jan 2011to Jan 2013
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 6 years
All sexes
No healthy volunteers
Child

Who may be able to join

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.

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Japan1 site

Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital
Okayama, 700-8558

Other trials in Japan

About this study

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

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.

Read the 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.

Conditions: Hypoplastic Left Heart Syndrome, Single Ventricle, Heart Failure
Being tested: Autologous cardiac progenitor cell transplantation, staged shunt procedure
Keywords: Cardiac progenitor cells, Cell therapy, Hypoplastic Left Heart Syndrome, Single Ventricle, Norwood, Sano modification, Glenn, Fontan
Medical subject headings: Hypoplastic Left Heart Syndrome, Univentricular Heart, Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Autologous cardiac progenitor cell transplantationProcedure or surgery
Also called Cardiosphere-derived cells
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 procedureProcedure or surgery
Norwood-Glenn, Glenn, or Fontan procedure will be applied

Study groups in NCT01273857
Study group	Role	What they receive
Control	Sham comparator	Subjects will undergo standard staged-procedures without cell infusion Receives: Procedure: staged shunt procedure
Cell infusion	Experimental	Subjects will receive transcoronary infusion of autologous cardiosphere-derived cells 1 month after staged shunt procedure Receives: Procedure: Autologous cardiac progenitor cell transplantation; Procedure: staged shunt procedure

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 3 months to 1 year after cell transplantation

Secondary outcomes (1)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2011Jan 2013

First posted11 Jan 2011 (estimated)
Study startJan 2011
Primary completionJan 2013
Study completionJan 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (8)Papers the sponsor has linked to this study.
Other trials for Hypoplastic Left Heart SyndromeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01273857
Sponsor's protocol ID: MHLW10103228
Acronym: TICAP
Status last verified: Nov 2021
First submitted: 10 Jan 2011
Last updated: 26 Nov 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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.
PubMed 19038683
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.
PubMed 18754813
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.
PubMed 17502484
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.
PubMed 17150190
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.
PubMed 25403163
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.
PubMed 39526355
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.
PubMed 29367212
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.
PubMed 26232942

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Long-term Safety Study Following to JRM-001 Treatment in Pediatric Patients With Congenital Heart Disease
Single Ventricle, Hypoplastic Left Heart Syndrome (HLHS)
RecruitingPhase 3
Cardiac Stem/Progenitor Cell Infusion in Univentricular Physiology (APOLLON Trial)
Hypoplastic Left Heart Syndrome, Single Ventricle
RecruitingObservational study
Prenatal Maternal Mental Health and Neurodevelopment in Congenital Heart Disease
Congenital Heart Disease, Cyanotic Congenital Heart Disease
Enrolling by invitation
Fetal Aortic Valvuloplasty for Evolving Hypoplastic Left Heart Syndrome
Hypoplastic Left Heart Syndrome
Active, not recruitingObservational study
Long-term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type
Heart Defects

All Hypoplastic Left Heart Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I Study of Cardiac Progenitor Cell Therapy in Patients With Single Ventricle Physiology
ClinicalTrials.gov ID: NCT01273857
Acronym / sponsor ID: TICAP / MHLW10103228
Conditions: Hypoplastic Left Heart Syndrome, Single Ventricle, Heart Failure
Keywords: Cardiac progenitor cells, Cell therapy, Hypoplastic Left Heart Syndrome, Single Ventricle, Norwood, Sano modification, Glenn, Fontan
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 14 participants (actual)
Lead sponsor: Okayama UniversityUniversity, hospital or other
Collaborators: National Cerebral and Cardiovascular Center, Japan
Study start: Jan 2011
Primary completion: Jan 2013 (actual)
Study completion: Jan 2013 (actual)
First posted: 11 Jan 2011 (estimated)
Results: Posted 15 Jun 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Control	Sham comparator	Procedure: staged shunt procedureSubjects will undergo standard staged-procedures without cell infusion
Cell infusion	Experimental	Procedure: Autologous cardiac progenitor cell transplantation, Procedure: staged shunt procedureSubjects will receive transcoronary infusion of autologous cardiosphere-derived cells 1 month after staged shunt procedure

Who may qualify

Ages: Up to 6 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (2 listed)

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.

Key exclusion criteria (7 listed)

Cardiogenic shock
Eisenmenger syndrome
Uncontrollable arrhythmia
Severe chronic diseases
Infections

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Autologous cardiac progenitor cell transplantationAlso: Cardiosphere-derived cellsPatients 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.	Procedure or surgery	Cell infusion
staged shunt procedureNorwood-Glenn, Glenn, or Fontan procedure will be applied	Procedure or surgery	Cell infusion, Control

Primary outcome

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.

1 secondary outcome

Serious Adverse Events
Time frame: 3 months to 1 year after cell transplantation

Results and safety

Results posted to the registry on 15 Jun 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Control	7	7
Cell Infusion	7	7

Primary outcome: 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. Number. Unit: participants

Measure	Control n = 7	Cell Infusion n = 7
Value	0	0

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 1 years. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Control	0 of 7 (0%)	0 of 7 (0%)	Not reported
Cell Infusion	0 of 7 (0%)	0 of 7 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 19038683Takehara 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.
Background: PubMed 18754813Tateishi 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.
Background: PubMed 17502484Tateishi 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.
Background: PubMed 17150190Tateishi 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 publication: PubMed 25403163Ishigami 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.
Derived from this study: PubMed 39526355Hirai 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.
Derived from this study: PubMed 29367212Sano 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.
Derived from this study: PubMed 26232942Tarui 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.

Related trials for Hypoplastic Left Heart Syndrome

RecruitingObservational study
Long-term Safety Study Following to JRM-001 Treatment in Pediatric Patients With Congenital Heart Disease
Single Ventricle, Hypoplastic Left Heart Syndrome (HLHS)
RecruitingPhase 3
Cardiac Stem/Progenitor Cell Infusion in Univentricular Physiology (APOLLON Trial)
Hypoplastic Left Heart Syndrome, Single Ventricle
RecruitingObservational study
Prenatal Maternal Mental Health and Neurodevelopment in Congenital Heart Disease
Congenital Heart Disease, Cyanotic Congenital Heart Disease
Enrolling by invitation
Fetal Aortic Valvuloplasty for Evolving Hypoplastic Left Heart Syndrome
Hypoplastic Left Heart Syndrome
Active, not recruitingObservational study
Long-term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type
Heart Defects

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Hidemasa Oh, M.D., Ph.D. principal investigator

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

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01273857, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2021.