Perinatal Brain Injury: Potential of Innovative NIRS to Optimize Hypothermia

The purpose of this study is to improve the ability of the investigators to monitor brain health in newborn babies at risk of brain injuries. The researchers will be using an investigational system of devices to non-invasively (that, is, without penetrating the skin), measure the amount of oxygen going to and being used by the brain. They will be taking some bedside research measurements during the babies' stay at the hospital. With these measurements, the intention is to study the role of oxygen in brain injury and test the efficacy of the research device and its potential as a permanent bedside diagnostic device.

Study Overview

• Status: Recruiting
• Conditions: Neonatal Encephalopathy; Hypoxic Ischemic Brain Injury
• Intervention / Treatment: Device: Near-Infrared Spectroscopy (NIRS)

Detailed Description

Neonatal encephalopathy (NE) due to hypoxia-ischemia is a major public health concern as it occurs in 6/1000 live term births and has devastating consequences. Many affected neonates suffer lifelong motor disabilities and epilepsy, but increasingly the high prevalence of cognitive and behavioral disabilities is becoming appreciated. In hypoxia-ischemia there is a decrease in blood and oxygen delivery, followed by reperfusion with transient energy recovery. What follows is a "window of opportunity" where excitotoxicity and associated increased cerebral metabolism eventually lead to secondary energy failure and irreversible cell death. In this window, therapeutic hypothermia (TH) is currently the only treatment available with proven efficacy. TH acts primarily by decreasing cerebral metabolism, thus preserving energy stores.

Although the current gold standard for brain injury detection is magnetic resonance imaging (MRI), MRI is impractical as a screening tool and cannot provide bedside monitoring to optimize individual responses to therapies. Commercially available continuous wave (CW) near infrared spectroscopy (NIRS) systems provide bedside measures of cerebral oxygen saturation (SO2) but SO2 alone cannot assess oxygen metabolism, as oxygen delivery is not taken into account. What is needed is a bedside tool that can monitor cerebral metabolism to detect elevations in metabolism that suggest evolving hypoxic-ischemic injury, and decreases in metabolism that suggest response to therapy. Cerebral oxygen consumption (CMRO2) is a direct measure of cerebral metabolism and therefore the investigators propose to measure an index of CMRO2 at the bedside using the innovative combination of Frequency Domain Near-Infrared Spectroscopy (FDNIRS) and Diffuse Correlation Spectroscopy (DCS). The initial studies from the investigators show that CMRO2 is elevated in neonates with MRI evidence of perinatal brain injury, and confirm that neonates on TH have significantly lower CMRO2 than normal controls. Following these exciting results, they now propose a feasibility study to determine if FDNIRS-DCS can screen for involvement, assess response to treatment, and predict outcomes in one of the largest neonatal populations requiring early screening and immediate intervention: neonatal encephalopathy. To assess early outcomes, the research team proposes an innovative combination of advanced neurobehavioral testing, regional FDNIRS-DCS measures and quantitative MRI analysis using MRIs obtained without sedation. If the hypotheses prove true, it will help in determining if bedside indices of CMRO2 provided by FDNIRS-DCS can optimize TH for individual neonates, thereby improving neurodevelopmental outcomes. Success at this stage will also allow exploration of the potential for FDNIRS-DCS to determine the additional benefits of emerging new treatments for NE and to screen for other treatable neonatal disorders.

• Study Type: Observational
• Enrollment (Estimated): 125

Contacts and Locations

• Study Contact: Name: Rutvi Vyas, MS; Phone Number: 857-218-5445; Email: rutvi.vyas@childrens.harvard.edu
• Study Contact Backup: Name: Sarah Blackwell; Phone Number: 857-218-5445; Email: sarah.blackwell@childrens.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
    • Boston, Massachusetts, United States, 02115
      • Not yet recruiting
      • Brigham and Women's Hospital
      • Contact: Rutvi Vyas, MS; Phone Number: 857-218-5445; Email: rutvi.vyas@childrens.harvard.edu
      • Contact: Francesca Yi; Phone Number: 857-218-5445; Email: francesca.yi@childrens.harvard.edu
      • Principal Investigator: Terrie Inder, MD
    • Boston, Massachusetts, United States, 02215
      • Not yet recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Rutvi Vyas, MS; Phone Number: 857-218-5445; Email: rutvi.vyas@childrens.harvard.edu
      • Contact: Francesca Yi; Phone Number: 857-218-5445; Email: francesca.yi@childrens.harvard.edu
      • Principal Investigator: Jonathan Litt, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Neonates must be > 33 weeks gestational age (GA) and meet inclusion criteria for one of the two groups:

1. Therapeutic Hypothermia (TH) Group:

   1. Undergo TH as part of their clinical management
   2. Parents consent to multiple measures in the first week of life.

2. No Therapeutic Hypothermia (no-TH) Group:

   1. Signs will be defined broadly as any one of the following which can be considered evidence of NE caused by HIE or other etiologies: i) Seizures alone or ii) any of the following: abnormal consciousness, difficulty maintaining respiration, difficulty feeding (presumed central origin), abnormal tone or reflexes.
   2. Parents consent to multiple measures in the first week of life.

Description

Inclusion criteria:

Neonates must be > 33 weeks gestational age (GA) and meet inclusion criteria for one of the two groups:

1. Therapeutic Hypothermia (TH) Group:

   1. Undergo TH as part of their clinical management
   2. Parents consent to multiple measures in the first week of life.

2. No Therapeutic Hypothermia (no-TH) Group:

   1. Signs will be defined broadly as any one of the following which can be considered evidence of NE caused by HIE or other etiologies: i) Seizures alone or ii) any of the following: abnormal consciousness, difficulty maintaining respiration, difficulty feeding (presumed central origin), abnormal tone or reflexes.
   2. Parents consent to multiple measures in the first week of life.

Exclusion criteria:

Exclusion criteria includes neonates born at GA ≤ 33 weeks or < 2.0 kg, with implanted devices or other devices that preclude the use of MRI will be excluded from the follow up MRI session.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare metrics such as hemoglobin oxygen saturation and cerebral metabolic rate of oxygen consumption as obtained from novel NIRS technology in neonates at risk for brain injury to normal controls.	The infants undergoing treatment with therapeutic hypothermia (TH) and those who are identified with neonatal brain injury but are not candidates for TH will be compared. Both groups will also be compared to normal controls.	early inpatient phase (0-2 months of age)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perform NIRS, MRI and Neurodevelopmental testing (using Bayley Scales for Infant Development) between 2-12 months.	Explore correlations between all NIRS and MRI measures, and neurodevelopmental outcome at 2-12 months.	up to 12 months of age
Perform Neurodevelopmental testing at 16-24 months using Bayley Scales for Infant Development.	Explore correlations between all NIRS and MRI measures, and neurodevelopmental outcomes.	up to 24 months of age

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Beth Israel Deaconess Medical Center; Brigham and Women's Hospital
• Investigators: Principal Investigator: Patricia Ellen Grant, MD, Boston Children's Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: May 10, 2016
• First Submitted That Met QC Criteria: June 3, 2016
• First Posted (Estimated): June 8, 2016

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Body Temperature Changes; Brain Injuries; Wounds and Injuries; Brain Diseases; Hypothermia
• Other Study ID Numbers: P00012473; R01HD076258-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO