Hypoxic Ischemic Brain InjuryNCT02793999
Perinatal Brain Injury: Potential of Innovative NIRS to Optimize Hypothermia
An observational study of Hypoxic Ischemic Brain Injury and Neonatal Encephalopathy, run by Boston Children's Hospital at 3 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages Up to 2 years
- Conditions the study is for
- Hypoxic Ischemic Brain Injury, Neonatal Encephalopathy
- What is being tested?
- Near-Infrared Spectroscopy (NIRS)
- Type of treatment
- Medical device
- How many people
- 125 participants
- Where
- 3 sitesUnited States
- Study dates
- May 2015to May 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 years
- All sexes
- No healthy volunteers
- Child
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.
Who may be able to join
- Neonates must be > 33 weeks gestational age (GA) and meet inclusion criteria for one of the two groups:
- Therapeutic Hypothermia (TH) Group:
- Undergo TH as part of their clinical management
- Parents consent to multiple measures in the first week of life.
- No Therapeutic Hypothermia (no-TH) Group:
- 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.
- Parents consent to multiple measures in the first week of life.
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
- Not yet recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Rutvi Vyas, MS, 857-218-5445, rutvi.vyas@childrens.harvard.edu
Francesca Yi, 857-218-5445, francesca.yi@childrens.harvard.edu
- Not yet recruiting
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Rutvi Vyas, MS, 857-218-5445, rutvi.vyas@childrens.harvard.edu
Francesca Yi, 857-218-5445, francesca.yi@childrens.harvard.edu
About this study
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.
Read the 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.
- Being tested
- Near-Infrared Spectroscopy (NIRS)
- Medical subject headings
- Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Near-Infrared Spectroscopy (NIRS)Device
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: early inpatient phase (0-2 months of age)
Secondary outcomes (2)
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.
Measured: 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.
Measured: up to 24 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2016 (estimated)
- Study startMay 2015
- Primary completionMay 2027 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypoxic Ischemic Brain InjuryStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 125 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Ellen Grant, Boston Children's Hospital
- Investigators
- Patricia Ellen Grant, MD, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02793999
- Sponsor's protocol ID
- P00012473
- Other IDs
- R01HD076258-02
- Status last verified
- Dec 2025
- First submitted
- 10 May 2016
- Last updated
- 10 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Perinatal Brain Injury: Potential of Innovative NIRS to Optimize Hypothermia
- ClinicalTrials.gov ID
- NCT02793999
- Acronym / sponsor ID
- P00012473
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 125 participants (estimated)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- May 2015
- Primary completion
- May 2027 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 8 Jun 2016 (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.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- Up to 2 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- 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.
Key inclusion criteria (7 listed)
- Neonates must be > 33 weeks gestational age (GA) and meet inclusion criteria for one of the two groups:
- Therapeutic Hypothermia (TH) Group:
- No Therapeutic Hypothermia (no-TH) Group:
Key exclusion criteria (1 listed)
- 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.
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 |
|---|---|---|
| Near-Infrared Spectroscopy (NIRS) | Device | – |
Primary outcome
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.
Time frame: early inpatient phase (0-2 months of age)
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.
2 secondary outcomes
Perform NIRS, MRI and Neurodevelopmental testing (using Bayley Scales for Infant Development) between 2-12 months.
Time frame: up to 12 months of age
Perform Neurodevelopmental testing at 16-24 months using Bayley Scales for Infant Development.
Time frame: up to 24 months of age
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2025.
- Individual participant dataSharing planned: No
Related trials for Hypoxic Ischemic Brain Injury
RecruitingPhase 2
The PROTECT-HIE Pilot Trial
Hypoxic-ischemic Encephalopathy (HIE)
RecruitingPhase 2/3
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RLS-0071 in Newborns With Moderate or Severe Hypoxic-Ischemic Encephalopathy Undergoing Therapeutic Hypothermia
Hypoxic-Ischemic Encephalopathy
Not yet recruiting
Levetiracetam as an Adjuvant Therapy to Hypothermia in Neonatal Asphyxia
Hypoxic Ischemic Encephalopathy of Newborn, Neuro-protection
Recruiting
Minimal Sedation Versus Standard Continuous Sedation After Out-of-Hospital Cardiac Arrest
Out-of-Hospital Cardiac Arrest, Hypoxic-Ischemic Brain Injury
Recruiting
Neuro-MoD: Neuroplasticity With Motor Development
Perinatal Brain Injury
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.
Patricia Ellen Grant, MD principal investigator
Boston Children's Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypoxic Ischemic Brain Injury and Neonatal Encephalopathy, run by Boston Children's Hospital at 3 sites 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 7 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 10 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rutvi Vyas, MS (857-218-5445, rutvi.vyas@childrens.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: early inpatient phase (0-2 months of age)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Dec 2025.