Hypoplastic Left Heart SyndromePhase 1NCT01445041
Safety and Feasibility Study of Umbilical Cord Blood Cells for Infants With Hypoplastic Left Heart Syndrome
A Phase 1 study testing Autologous Umbilical Cord Blood in people with Hypoplastic Left Heart Syndrome, run by Michael Cotten at 1 site in United States.
Trial summary
Further study details as provided by Duke University: Purpose: To evaluate the feasibility and safety of collecting and infusing autologous umbilical cord blood (UCB) in newborn infants with hypoplastic left heart syndrome (HLHS). Read more about this study
- Who is it for?
- Ages Up to 2 days
- Conditions the study is for
- Hypoplastic Left Heart Syndrome
- What is being tested?
- Autologous Umbilical Cord Blood
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2011to 15 Apr 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 2 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants > 35 weeks gestational age.
- Diagnosis: Hypoplastic Left Heart Syndrome.
- Autologous umbilical cord blood available with a minimum total nucleated cell dose of 1 x 10e7 cells/kg.
- Parental Consent.
Who cannot join
- Chromosomal anomalies identified before the time of infusion.
- Chromosomal anomalies or congenital anomalies that would prohibit clinicians from initiating surgical repair of the congenital heart defect.
- Infant is determined by clinical staff to be non-viable and will not receive aggressive care. (No member on the study team will be involved in determining the viability of the neonate.)
- Autologous umbilical cord blood unit has any of the following:
- Total nuclear cell count < 1 x 10e7.
- Positive maternal infectious serology (except CMV).
Show all 10Show fewer
- Evidence of infectious contamination of the cord blood unit.
- Evidence of genetic disease.
- Unable to obtain parental consent.
- Mother < 18 years old.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Autologous Cord Blood Cells for Patients With HLHS: Phase I Study of Feasibility and Safety
Further study details as provided by Duke University:
Purpose: To evaluate the feasibility and safety of collecting and infusing autologous umbilical cord blood (UCB) in newborn infants with hypoplastic left heart syndrome (HLHS).
Read more
Study Rationale and Hypotheses: The major goal of this study is to determine whether infusion of autologous UCB cells in neonates with hypoplastic left heart syndrome is feasible and safe. The rationale for the study and for the potential benefit of UCB is based upon the following hypotheses:
- Infants with HLHS have significant neural injury evidenced from both prenatal and early antenatal brain MRI findings and infusion of UCB cells may lessen neural injury. Although the exact mechanism is unknown, UCB cell infusion may ameliorate neural injury via paracrine and anti-inflammatory effects that enhance post injury repair and may promote endogenous functional compensation of other cortical areas resulting in significant clinical improvements.
- UCB cells may also enhance cardiac function, minimize scar formation, and reverse detrimental remodeling after cardiac injury.
Read the detailed description
The purpose of this pilot study is to evaluate the safety and feasibility of infusions of autologous (the patient's own)umbilical cord blood cells in neonates with hypoplastic left heart syndrome. This is a prospective, randomized Phase I trial designed to assess the safety and feasibility of autologous UCB reinfusion in neonates with Hypoplastic Left Heart Syndrome (HLHS). Neonates who are identified prenatally as having a cardiac lesion consistent with HLHS will be referred to Duke Cardiology for further evaluation. If they meet inclusion criteria, UCB will be collected at the time of delivery and processed (red blood cell- and volume-reduced) for reinfusion. All enrolled infants will receive a dose of fresh UCB cells pre-operatively and ½ of the enrolled infants will be randomly selected to receive a second dose of frozen and thawed UCB cells after stage 1 palliation (5-35 days post-operatively) and a third dose of frozen and thawed UCB cells 2 to 4 weeks after the 2nd infusion. Neurodevelopmental outcome measures will be assessed at 1 month after discharge, at 4-6 months old and 12 months. The results of MRI's and echocardiograms that are obtained per clinical routine will be analyzed and described in study reports.
- Conditions
- Hypoplastic Left Heart Syndrome
- Being tested
- Autologous Umbilical Cord Blood
- Keywords
- Hypoplastic Left Heart Syndrome, Autologous Umbilical Cord Blood, Newborn Infants
- Medical subject headings
- Hypoplastic Left Heart Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Umbilical Cord BloodBiological
Infants who meet study enrollment criteria for hypoplastic left heart syndrome in the neonatal period will receive 1 infusion of their own volume reduced cord blood cells. The dose for each infusion is 5x10e7 cells/kg.
Autologous Umbilical Cord BloodBiological
Infants who meet study enrollment criteria for hypoplastic left heart syndrome in the neonatal period will receive 3 infusions of their own volume reduced cord blood cells. The first infusion will be a fresh, volume-reduced infusion and the subsequent infusions will be thawed and washed infusions. The dose for each infusion is 5x10e7 cells/kg.
| Study group | Role | What they receive |
|---|---|---|
| Single infusion of UCB | Experimental | (autologous red blood cell and volume reduced cord blood cells) Receives: Biological: Autologous Umbilical Cord Blood |
| Three infusions of UCB | Experimental | (autologous red blood cell and volume reduced cord blood cells) Receives: Biological: Autologous Umbilical Cord Blood |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse event rates occurring in the pilot study population. The investigators will compare infusion outcomes of infants infused with frozen cells and infants infused with non-frozen cells.
Measured: During Infusions (First 2 months of life)
Secondary outcomes (1)
Feasibility and preliminary efficacy
Feasibility: volume of cord blood, cell viability, time to prepare/infuse fresh cells and frozen-thawed cells.
Preliminary efficacy: neurodevelopmental outcomes at 9 - 12 months, cardiac function as assessed clinically.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2011 (estimated)
- Study start1 Sep 2011
- Primary completion15 Apr 2016
- Study completion15 Apr 2016
Why it stopped: Funding Period Ended
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)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
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael Cotten
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Michael Cotten, Duke University
- Investigators
- Charles M Cotten, MD MHS, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01445041
- Sponsor's protocol ID
- Pro00024650
- Status last verified
- May 2024
- First submitted
- 15 Sep 2011
- Last updated
- 16 May 2024
- Results posted
- No
- Data monitoring committee
- No
Publications
Martin PL, Carter SL, Kernan NA, Sahdev I, Wall D, Pietryga D, Wagner JE, Kurtzberg J. Results of the cord blood transplantation study (COBLT): outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases. Biol Blood Marrow Transplant. 2006 Feb;12(2):184-94. doi: 10.1016/j.bbmt.2005.09.016.
PubMed 16443516Kurtzberg J, Lyerly AD, Sugarman J. Untying the Gordian knot: policies, practices, and ethical issues related to banking of umbilical cord blood. J Clin Invest. 2005 Oct;115(10):2592-7. doi: 10.1172/JCI26690.
PubMed 16200191Escolar ML, Poe MD, Provenzale JM, Richards KC, Allison J, Wood S, Wenger DA, Pietryga D, Wall D, Champagne M, Morse R, Krivit W, Kurtzberg J. Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease. N Engl J Med. 2005 May 19;352(20):2069-81. doi: 10.1056/NEJMoa042604.
PubMed 15901860Staba SL, Escolar ML, Poe M, Kim Y, Martin PL, Szabolcs P, Allison-Thacker J, Wood S, Wenger DA, Rubinstein P, Hopwood JJ, Krivit W, Kurtzberg J. Cord-blood transplants from unrelated donors in patients with Hurler's syndrome. N Engl J Med. 2004 May 6;350(19):1960-9. doi: 10.1056/NEJMoa032613.
PubMed 15128896McGraw P, Liang L, Escolar M, Mukundan S, Kurtzberg J, Provenzale JM. Krabbe disease treated with hematopoietic stem cell transplantation: serial assessment of anisotropy measurements--initial experience. Radiology. 2005 Jul;236(1):221-30. doi: 10.1148/radiol.2353040716.
PubMed 15987975Mahle WT, Tavani F, Zimmerman RA, Nicolson SC, Galli KK, Gaynor JW, Clancy RR, Montenegro LM, Spray TL, Chiavacci RM, Wernovsky G, Kurth CD. An MRI study of neurological injury before and after congenital heart surgery. Circulation. 2002 Sep 24;106(12 Suppl 1):I109-14.
PubMed 12354718
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autologous Cord Blood Cells for Patients With HLHS: Phase I Study of Feasibility and Safety
- ClinicalTrials.gov ID
- NCT01445041
- Acronym / sponsor ID
- Pro00024650
- Conditions
- Hypoplastic Left Heart Syndrome
- Keywords
- Hypoplastic Left Heart Syndrome, Autologous Umbilical Cord Blood, Newborn Infants
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding Period Ended
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Michael CottenUniversity, hospital or other
- Study start
- 1 Sep 2011 (actual)
- Primary completion
- 15 Apr 2016 (actual)
- Study completion
- 15 Apr 2016 (actual)
- First posted
- 3 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Further study details as provided by Duke University:
Purpose: To evaluate the feasibility and safety of collecting and infusing autologous umbilical cord blood (UCB) in newborn infants with hypoplastic left heart syndrome (HLHS).
Study Rationale and Hypotheses: The major goal of this study is to determine whether infusion of autologous UCB cells in neonates with hypoplastic left heart syndrome is feasible and safe. The rationale for the study and for the potential benefit of UCB is based upon the following hypotheses:
- Infants with HLHS have significant neural injury evidenced from both prenatal and early antenatal brain MRI findings and infusion of UCB cells may lessen neural injury. Although the exact mechanism is unknown, UCB cell infusion may ameliorate neural injury via paracrine and anti-inflammatory effects that enhance post injury repair and may promote endogenous functional compensation of other cortical areas resulting in significant clinical improvements.
- UCB cells may also enhance cardiac function, minimize scar formation, and reverse detrimental remodeling after cardiac injury.
Detailed description
The purpose of this pilot study is to evaluate the safety and feasibility of infusions of autologous (the patient's own)umbilical cord blood cells in neonates with hypoplastic left heart syndrome. This is a prospective, randomized Phase I trial designed to assess the safety and feasibility of autologous UCB reinfusion in neonates with Hypoplastic Left Heart Syndrome (HLHS). Neonates who are identified prenatally as having a cardiac lesion consistent with HLHS will be referred to Duke Cardiology for further evaluation. If they meet inclusion criteria, UCB will be collected at the time of delivery and processed (red blood cell- and volume-reduced) for reinfusion. All enrolled infants will receive a dose of fresh UCB cells pre-operatively and ½ of the enrolled infants will be randomly selected to receive a second dose of frozen and thawed UCB cells after stage 1 palliation (5-35 days post-operatively) and a third dose of frozen and thawed UCB cells 2 to 4 weeks after the 2nd infusion. Neurodevelopmental outcome measures will be assessed at 1 month after discharge, at 4-6 months old and 12 months. The results of MRI's and echocardiograms that are obtained per clinical routine will be analyzed and described in study reports.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Single infusion of UCB | Experimental | Biological: Autologous Umbilical Cord Blood(autologous red blood cell and volume reduced cord blood cells) |
| Three infusions of UCB | Experimental | Biological: Autologous Umbilical Cord Blood(autologous red blood cell and volume reduced cord blood cells) |
Who may qualify
- Ages
- Up to 2 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Infants > 35 weeks gestational age.
- Diagnosis: Hypoplastic Left Heart Syndrome.
- Autologous umbilical cord blood available with a minimum total nucleated cell dose of 1 x 10e7 cells/kg.
- Parental Consent.
Key exclusion criteria (10 listed)
- Chromosomal anomalies identified before the time of infusion.
- Chromosomal anomalies or congenital anomalies that would prohibit clinicians from initiating surgical repair of the congenital heart defect.
- Infant is determined by clinical staff to be non-viable and will not receive aggressive care. (No member on the study team will be involved in determining the viability of the neonate.)
- Autologous umbilical cord blood unit has any of the following:
- Unable to obtain parental consent.
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 Umbilical Cord BloodInfants who meet study enrollment criteria for hypoplastic left heart syndrome in the neonatal period will receive 1 infusion of their own volume reduced cord blood cells. The dose for each infusion is 5x10e7 cells/kg. | Biological | Single infusion of UCB |
| Autologous Umbilical Cord BloodInfants who meet study enrollment criteria for hypoplastic left heart syndrome in the neonatal period will receive 3 infusions of their own volume reduced cord blood cells. The first infusion will be a fresh, volume-reduced infusion and the subsequent infusions will be thawed and washed infusions. The dose for each infusion is 5x10e7 cells/kg. | Biological | Three infusions of UCB |
Primary outcome
Adverse event rates occurring in the pilot study population. The investigators will compare infusion outcomes of infants infused with frozen cells and infants infused with non-frozen cells.
Time frame: During Infusions (First 2 months of life)
1 secondary outcome
Feasibility and preliminary efficacy
Time frame: 1 year
Results and safety
The study was stopped early (reason given: Funding Period Ended). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
- Background: PubMed 16443516Martin PL, Carter SL, Kernan NA, Sahdev I, Wall D, Pietryga D, Wagner JE, Kurtzberg J. Results of the cord blood transplantation study (COBLT): outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases. Biol Blood Marrow Transplant. 2006 Feb;12(2):184-94. doi: 10.1016/j.bbmt.2005.09.016.
- Background: PubMed 16200191Kurtzberg J, Lyerly AD, Sugarman J. Untying the Gordian knot: policies, practices, and ethical issues related to banking of umbilical cord blood. J Clin Invest. 2005 Oct;115(10):2592-7. doi: 10.1172/JCI26690.
- Background: PubMed 15901860Escolar ML, Poe MD, Provenzale JM, Richards KC, Allison J, Wood S, Wenger DA, Pietryga D, Wall D, Champagne M, Morse R, Krivit W, Kurtzberg J. Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease. N Engl J Med. 2005 May 19;352(20):2069-81. doi: 10.1056/NEJMoa042604.
- Background: PubMed 15128896Staba SL, Escolar ML, Poe M, Kim Y, Martin PL, Szabolcs P, Allison-Thacker J, Wood S, Wenger DA, Rubinstein P, Hopwood JJ, Krivit W, Kurtzberg J. Cord-blood transplants from unrelated donors in patients with Hurler's syndrome. N Engl J Med. 2004 May 6;350(19):1960-9. doi: 10.1056/NEJMoa032613.
- Background: PubMed 15987975McGraw P, Liang L, Escolar M, Mukundan S, Kurtzberg J, Provenzale JM. Krabbe disease treated with hematopoietic stem cell transplantation: serial assessment of anisotropy measurements--initial experience. Radiology. 2005 Jul;236(1):221-30. doi: 10.1148/radiol.2353040716.
- Background: PubMed 12354718Mahle WT, Tavani F, Zimmerman RA, Nicolson SC, Galli KK, Gaynor JW, Clancy RR, Montenegro LM, Spray TL, Chiavacci RM, Wernovsky G, Kurth CD. An MRI study of neurological injury before and after congenital heart surgery. Circulation. 2002 Sep 24;106(12 Suppl 1):I109-14.
- Carolinas Cord Blood Bank web pageLink provided by the sponsor.
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.
Charles M Cotten, MD MHS principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Autologous Umbilical Cord Blood in people with Hypoplastic Left Heart Syndrome, run by Michael Cotten at 1 site in United States.
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 4 inclusion and 10 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: stopped early, as of the sponsor's last update on 16 May 2024. 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 United States. 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. 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?
The study was stopped early (reason given: Funding Period Ended). Results are not available in the source record.
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?
Adverse event rates occurring in the pilot study population. The investigators will compare infusion outcomes of infants infused with frozen cells and infants infused with non-frozen cells. (time frame: During Infusions (First 2 months of life)). 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 NCT01445041, which also lists 6 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 16 May 2024.