Autologous Umbilical Cord Blood Treatment of Neonate With CHD

Congenital Heart Disease Clinical Trial

Official title:

Pilot Study to Assess the Efficacy of Autologous Umbilical Cord Blood Treatment of Brain and Heart Injury in Neonates With Congenital Heart Defect

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03558269
• Other study ID #: 3757-16-SMC
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 1, 2019
• Est. completion date: April 1, 2023

Study information

• Verified date: January 2021
• Source: Sheba Medical Center
• Contact: Omer Bar-Yosef, M.D.-Ph.D.
• Phone: 972-3-5302687
• Email: omer.baryosef[@]sheba.health.gov.il
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: April 1, 2023
• Est. primary completion date: May 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 14 Days

Eligibility

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.

Related Conditions & MeSH terms

• Brain Injuries
• Cardiac Output, Low
• Congenital Heart Disease
• Heart Diseases
• Infant, Newborn, Diseases
• Low Cardiac Output Syndrome
• Neonatal Disorder

Intervention

Biological:
• Autlogous 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.

Locations

Country	Name	City	State
Israel	Sheba Medical Center	Ramat Gan

Sponsors (1)

Lead Sponsor	Collaborator
Sheba Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (3)

Alotaibi M, Long T, Kennedy E, Bavishi S. The efficacy of GMFM-88 and GMFM-66 to detect changes in gross motor function in children with cerebral palsy (CP): a literature review. Disabil Rehabil. 2014;36(8):617-27. doi: 10.3109/09638288.2013.805820. Epub 2013 Jun 26. Review. — View Citation

Dimitropoulos A, McQuillen PS, Sethi V, Moosa A, Chau V, Xu D, Brant R, Azakie A, Campbell A, Barkovich AJ, Poskitt KJ, Miller SP. Brain injury and development in newborns with critical congenital heart disease. Neurology. 2013 Jul 16;81(3):241-8. doi: 10 — View Citation

Kwong AKL, Fitzgerald TL, Doyle LW, Cheong JLY, Spittle AJ. Predictive validity of spontaneous early infant movement for later cerebral palsy: a systematic review. Dev Med Child Neurol. 2018 May;60(5):480-489. doi: 10.1111/dmcn.13697. Epub 2018 Feb 22. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neuroimaging of the brain before and after the surgery (ref 1)	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.	The time frame between MRI before and after surgery is 10-13 days
Secondary	Neuro-development at one month	General movements assessment (ref 2)	One month
Secondary	Neuro-development at six month	Gross Motor Function Measure 66 (ref 3)	6 months
Secondary	Neuro-development at 12 month	Gross Motor Function Measure 66 (ref 3)	12months