Brain Injuries, Congenital Heart Disease, Low Cardiac Output Syndrome, Neonatal Disorder
Conditions
Keywords
Autologous Umbilical cord blood infusion, Congenital Heart Disease, Brain Injuries, Low Cardiac Output Syndrome, Neonatal Disorder
Brief summary
The aim of the study is to evaluate the feasibility and safety and efficacy of collecting and infusing autologous umbilical cord blood (UCB) in newborn infants with hypoplastic left heart syndrome (HLHS) and transposition of great arteries (TGA). Rationale: Neonates with HLHS and TGA have significant brain injury as demonstrated by peri-surgical MRI. Moreover, there a substantial tendency to suffer from chronic cardiac condition as low cardiac output state and valvular insufficiency. Treatment of neonates after hypoxic ischemic injury at birth with autologous UCB was shown to safe and improved developmental outcome. The effect of UCB is most likely achieved by reduction of free radicals injury and pro-inflammatory and apoptotic process. Hypothesis: Treatment with UCB immediately after the first cardiac surgey, with in the first week life will reduce the brain injury demonstrated by MRI and reduce the choronic cardiac problems
Detailed description
The aim of this pilot study is to evaluate the safety and feasibility of infusion of autologous umbilical cord blood (UCB) in neonates with with hypoplastic left heart syndrome (HLHS) or transposition of great arteries (TGA). This is a prospective, matched control study, Phase I-II trial to evaluate the safety and efficacy of autologous UCB infusion in neonates with HLHS or TGA. The study group will consist of neonate that were diagnosed by prenatal fetal ultrasound with HLHS or TGA and their UCB was collected at the time of delivery. The study group will include the patients with UCB and the control group will be patients without UCB. All patients will have their surgery within 2 weeks from birth. The UCB will be infused to the patients in study group as soon as the patient has stabilized after the surgery and not more than 7 days after surgery. Both groups will be followed similarity: During hospitalization: Neurological and cardiac evaluation a day before surgery, 7 days after surgery and at discharge. Blood tests for immune and growth factors a day before surgery, at the time of infusion (or intended infusion for the control group) ,1 and 7 days after infusion. have a cardiac and brain MRI before the surgery and within 14 days after surgery. Brain and cardiac MRI before surgery, 7-14 days after surgery. Ambulatory follow up (similar to routine follow up): Cardiac and neuro-developmental evaluation at 1,6,12 month Blood tests for immune and growth factors at 1 month
Interventions
BIOLOGICALAutlogous UCB infusion
Infants delivered with hypoplastic left heart syndrome and transposition of great arteries undergoing surgery in the 1st 2 weeks of life will be treated with autologous UCB after the surgery. Each group will be followed by MRI before (1-3 days) and after the surgery between at 10 POD. Developmental follow up will be done at 1, 6 and 12 months. Another brain MRI will be done at 6 months of age.
Sponsors
Sheba Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The outcome assessor will not be exposed to the participant group
Eligibility
Sex/Gender
ALL
Age
3 Days to 14 Days
Healthy volunteers
No
Inclusion criteria
1. At least 35 weeks of gestation 2. Prenatal diagnosis of HLHS including mitral stenosis/atresia, aortic stenosis/atresia, arch hypoplasia and the presence of hypoplastic left ventricle with or without VSD. 3. Norwood procedure will take place within 14 days from birth. 4. Treatment with cord blood should be given within 7 days after surgery. 5. Parental informed consent for collection of umbilical cord blood.
Exclusion criteria
1. Total nucleated cells (TNC) lower than 1X107 in the collected umbilical cord blood unit. 2. Infected umbilical cord blood unit. 3. Parents refusal to continue in the study at any stage.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neuroimaging of the brain before and after the surgery (ref 1) | The time frame between MRI before and after surgery is 10-13 days | Change in MRI of the brain before (between 1-3 days) and after (10 days) the surgery between the intervention and control group. The change will be quantified by MRI brain injury severity (BIS) score quantifying white matter injury, stroke and brain hemorrhage. Diffusion tensor imaging measures will also be quantified by using average diffusivity and fractional anisotropy calculated from frontal, parietal, temporal and occipital white matter. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neuro-development at one month | One month | General movements assessment (ref 2) |
| Neuro-development at six month | 6 months | Gross Motor Function Measure 66 (ref 3) |
| Neuro-development at 12 month | 12months | Gross Motor Function Measure 66 (ref 3) |
Countries
Israel
Contacts
Primary ContactOmer Bar-Yosef, M.D.-Ph.D.
Backup ContactAmir Vardi, M.D.
Outcome results
None listed