TICAP: Transcoronary Infusion of Cardiac Progenitor Cells in Patients With Single Ventricle Physiology
Study Details
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 |
|---|---|---|
|
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
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 Names:
Procedure: staged shunt procedure
Norwood-Glenn, Glenn, or Fontan procedure will be applied
|
Outcome Measures
Primary Outcome Measures
- Feasibility Evaluation and Major Cardiac Adverse Events Related to Transcoronary Infusion of Cardiac Progenitor Cells [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
- Serious Adverse Events [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
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
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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
Study Documents (Full-Text)
None provided.More Information
Additional Information:
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, 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.
- MHLW10103228
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Control | Cell Infusion |
|---|---|---|
| Arm/Group Description | Subjects will undergo standard staged-procedures without cell infusion staged shunt procedure: Norwood-Glenn, Glenn, or Fontan procedure will be applied | Subjects will receive transcoronary infusion of autologous cardiosphere-derived cells 1 month after staged shunt 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 |
| Period Title: Overall Study | ||
| STARTED | 7 | 7 |
| COMPLETED | 7 | 7 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Control | Cell Infusion | Total |
|---|---|---|---|
| Arm/Group Description | Subjects will undergo standard staged-procedures without cell infusion staged shunt procedure: Norwood-Glenn, Glenn, or Fontan procedure will be applied | Subjects will receive transcoronary infusion of autologous cardiosphere-derived cells 1 month after staged shunt 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 | Total of all reporting groups |
| Overall Participants | 7 | 7 | 14 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
1.5
(1.7)
|
2.1
(1.2)
|
1.7
(1.5)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
3
42.9%
|
3
42.9%
|
6
42.9%
|
| Male |
4
57.1%
|
4
57.1%
|
8
57.1%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| Japanese |
7
100%
|
7
100%
|
14
100%
|
| Region of Enrollment (participants) [Number] | |||
| Japan |
7
100%
|
7
100%
|
14
100%
|
Outcome Measures
| Title | Feasibility Evaluation and Major Cardiac Adverse Events Related to Transcoronary Infusion of Cardiac Progenitor Cells |
|---|---|
| Description | 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. |
| Time Frame | 3 months to 1 year after cell transplantation |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Control | Cell Infusion |
|---|---|---|
| Arm/Group Description | Subjects will undergo standard staged-procedures without cell infusion staged shunt procedure: Norwood-Glenn, Glenn, or Fontan procedure will be applied | Subjects will receive transcoronary infusion of autologous cardiosphere-derived cells 1 month after staged shunt 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 |
| Measure Participants | 7 | 7 |
| Number [participants] |
0
0%
|
0
0%
|
| Title | Serious Adverse Events |
|---|---|
| Description | The incidence of hospitalization for heart failure, ventricular arrhythmia, general infection, and renal and hepatic dysfunction by CDC treatment. |
| Time Frame | 3 months to 1 year after cell transplantation |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Control | Cell Infusion |
|---|---|---|
| Arm/Group Description | Subjects will undergo standard staged-procedures without cell infusion staged shunt procedure: Norwood-Glenn, Glenn, or Fontan procedure will be applied | Subjects will receive transcoronary infusion of autologous cardiosphere-derived cells 1 month after staged shunt 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 |
| Measure Participants | 7 | 7 |
| Number [participants] |
0
0%
|
0
0%
|
Adverse Events
| Time Frame | 1 years | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Control | Cell Infusion | ||
| Arm/Group Description | Subjects will undergo standard staged-procedures without cell infusion staged shunt procedure: Norwood-Glenn, Glenn, or Fontan procedure will be applied | Subjects will receive transcoronary infusion of autologous cardiosphere-derived cells 1 month after staged shunt 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 | ||
All Cause Mortality |
||||
| Control | Cell Infusion | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Control | Cell Infusion | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/7 (0%) | 0/7 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Control | Cell Infusion | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/7 (0%) | 0/7 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Prof. Hidemasa Oh |
|---|---|
| Organization | Okayama University Hospital |
| Phone | +81-086-235-6506 |
| hidemasa@md.okayama-u.ac.jp |
- MHLW10103228