A Multi-site Study of Autologous Cord Blood Cells for Hypoxic Ischemic Encephalopathy ((HIE))

• ClinicalTrials.gov Identifier: NCT02612155
• Recruitment Status: Completed
• First Posted: November 23, 2015
• Results First Posted: August 25, 2020
• Last Update Posted: August 25, 2020
• Sponsor: Michael Cotten
• Collaborator: The Robertson Foundation
• Information provided by (Responsible Party): Michael Cotten, Duke University

Study Description

Brief Summary:

This study will test the safety and efficacy of an infusion of a baby's own (autologous) umbilical cord blood as compared with placebo in babies born with history and signs of hypoxic-ischemic brain injury.

Condition or disease	Intervention/treatment	Phase
Moderate or Severe Hypoxic-ischemic Encephalopathy in Newborns	Biological: Infusion of autologous cord blood; Biological: Placebo	Phase 2

Detailed Description:

The purpose of this phase II study is to assess the safety and efficacy of up to two intravenous infusions of autologous volume and red blood cell reduced nucleated umbilical cord blood cells as compared with placebo in neonates with neonatal encephalopathy undergoing hypothermia treatment. Efficacy will be estimated by one year survival and score on Bayley III scores in all three domains equal to or greater than 85. This will be a randomized, double-blind, placebo controlled multi-site trial of up to 160 infants who qualify for cooling.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II Multi-site Study of Autologous Cord Blood Cells for Hypoxic (HIE)
• Actual Study Start Date: March 30, 2017
• Actual Primary Completion Date: August 5, 2019
• Actual Study Completion Date: August 5, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention cell recipients; Experimental: infusions: infants with moderate to severe hypoxic ischemic encephalopathy, begin cooling, and have autologous nucleated cord blood cells available for infusion will receive up to two infusions. Outcomes will be measured at 22-26 months by neurodevelopment assessment	Biological: Infusion of autologous cord blood; Infants who meet study enrollment criteria will receive up to 2 infusions of their own volume reduced cord blood cells. The number of doses will be determined by the amount of available cord blood cells.
Placebo Comparator: Placebo recipients; Control: infants with moderate to severe hypoxic ischemic encephalopathy, begin cooling, and have cord blood available for infusion will receive placebo (a mix of autologous cord blood red blood cells and plasma) infusions. Outcomes will be measured at 22-26 months by neurodevelopment assessment	Biological: Placebo; Infants who meet study enrollment criteria will receive up to 2 placebo infusions composed of an equivalent volume (volume of product that would have been administered if the infant randomized to the intervention arm) of packed red blood cells (PRBCs) from the red cell compartment of the separated cord blood unit.

Outcome Measures

Primary Outcome Measures :

1. Survival at One Year [ Time Frame: 1 year ]
   Number of participants alive at one year.
2. Number of Participants With Bayley III Scores in All Three Domains > or Equal to 85 [ Time Frame: 1 year ]
   The Bayley is a standardized, norm-referenced measure that assesses development in Cognitive, Language and Motor domains. Composite standard scores can be derived that have a mean of 100 and a standard deviation of 15.

Secondary Outcome Measures :

1. Mortality Rate [ Time Frame: 1 year ]
   (Number of participants who died/total number of participants) x 100
2. Number of Subjects Who Experience Seizures [ Time Frame: During hospitalization, approximately 4-92 days ]
3. Number of Subjects Who Require iNO (Inhaled Nitric Oxide) Use [ Time Frame: During hospitalization, approximately 4-92 days ]
4. Number of Subjects Who Require ECMO [ Time Frame: During hospitalization, approximately 4-92 days ]
   ECMO (extracorporeal membrane oxygenation) is a technique of providing prolonged cardiac and respiratory support to persons whose heart and lungs are unable to provide an adequate amount of gas exchange or perfusion to sustain life.
5. Number of Subjects Who Require Gastrostomy Tube (G-tube) Feeding [ Time Frame: During hospitalization, approximately 4-92 days ]
6. Number of Subjects Who Are Discharged on Anti-epileptic Medication [ Time Frame: At hospital discharge, approximately 4-92 days ]

Eligibility Criteria

• Ages Eligible for Study: up to 6 Hours (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. NICHD Neonatal Research Network Hypothermia Trial inclusion criteria
2. Mothers must have consented or given verbal assent for cord blood collection at delivery, and cord blood must be available for volume and red blood cell reduction before 45 hours of age
3. The infant must be able to receive at least one dose of autologous cord blood before 48 hours of age
4. All infants must have signs of encephalopathy within 6 hours of age

Exclusion Criteria:

1. Major congenital or chromosomal abnormalities
2. Severe growth restriction (birth weight <1800 g)
3. Opinion by attending neonatologist that the study may interfere with treatment or safety of subject
4. Moribund neonates for whom no further treatment is planned
5. Infants born to mothers are known to be HIV, Hepatitis B, Hepatitis C or who have active syphilis or CMV infection in pregnancy
6. Infants suspected of overwhelming sepsis
7. ECMO initiated or likely in the first 48 hours of life

Contacts and Locations

Locations

United States, Alabama

University of Alabama Birmingham

Birmingham, Alabama, United States, 35233

United States, Florida

University of Florida Gainesville

Gainesville, Florida, United States, 32608

United States, Massachusetts

MassGeneral Hospital for Children

Boston, Massachusetts, United States, 02114

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

United States, Michigan

Wayne State University Hospital

Detroit, Michigan, United States, 48201

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

University of Florida at Jacksonville

Jacksonville, North Carolina, United States, 32209

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Michael Cotten

The Robertson Foundation

Investigators

• Principal Investigator: Michael Cotten, MD; Duke University

  Study Documents (Full-Text)

Documents provided by Michael Cotten, Duke University:

Study Protocol and Statistical Analysis Plan  [PDF] February 6, 2018

More Information

Publications:

Cotten CM, Murtha AP, Goldberg RN, Grotegut CA, Smith PB, Goldstein RF, Fisher KA, Gustafson KE, Waters-Pick B, Swamy GK, Rattray B, Tan S, Kurtzberg J. Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy. J Pediatr. 2014 May;164(5):973-979.e1. doi: 10.1016/j.jpeds.2013.11.036. Epub 2013 Dec 31.

Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD, Finer NN, Carlo WA, Duara S, Oh W, Cotten CM, Stevenson DK, Stoll BJ, Lemons JA, Guillet R, Jobe AH; National Institute of Child Health and Human Development Neonatal Research Network. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005 Oct 13;353(15):1574-84. doi: 10.1056/NEJMcps050929.

Escolar 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.

• Responsible Party: Michael Cotten, Associate Professor, Duke University
• ClinicalTrials.gov Identifier: NCT02612155
• Other Study ID Numbers: Pro00066647
• First Posted: November 23, 2015
• Results First Posted: August 25, 2020
• Last Update Posted: August 25, 2020
• Last Verified: August 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Michael Cotten, Duke University:

Hypoxic-ischemic encephalopathy; autologous cord blood cells; newborn infants

Additional relevant MeSH terms:

Brain Ischemia; Hypoxia-Ischemia, Brain; Ischemia; Hypoxia; Hypoxia, Brain; Brain Diseases; Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases