DCS Study in Extremely Premature Newborns

The Continuous Monitoring of Cerebral Function, Oxygen Perfusion and Consumption in Extremely Premature Newborns

We are attempting to improve the cerebral monitoring of extremely low gestational age (ELGA) infants, such that in the future, real-time monitoring will be possible, to aid clinicians in their management of these infants. We wish to establish a new NIRS device, diffuse correlation spectroscopy (DCS), as a safe, noninvasive and informative bedside tool for assessing and monitoring brain health in ELGA infants during the first few days of life. It is hoped that this method will provide detailed information on changes in oxygen consumption and metabolism, and cerebral perfusion. This technique will have wide applicability, but for this research study we wish to focus on the effect of blood flow instabilities, intermittent hypotension and hypoxic episodes, pressure passive CBF periods, and hypoperfusion on the preterm brain during the first days of life, and their relationship with incidence of intraventricular hemorrhage (IVH). We aim to recruit 100 premature infants to obtain data to:

1. Test the feasibility of NIRS-DCS to monitor cerebral activity, perfusion and oxygen consumption in extremely premature infants during the first week of life.
2. To assess if these baseline values are impacted by intermittent hypoxic episodes.
3. To assess if cerebral blood flow disturbances correlate with incidence of intraventricular hemorrhage.
4. Correlate the NIRS-DCS findings with clinical outcome at hospital discharge.

Study Overview

• Status: Recruiting
• Conditions: Premature Birth; Intracerebral Hemorrhage; Infant, Small for Gestational Age; Extremely Low Birth Weight
• Intervention / Treatment: Device: Diffuse Correlation Spectroscopy (DCS); Device: Amplitude Integrated Electroencephalography (aEEG)

Detailed Description

Infants born at an extremely low gestational age (<29 weeks GA) (ELGA) are at risk for developing any grade of intraventricular hemorrhage (IVH). In association with IVH, ELGA infants may develop associated neuropathology including periventricular hemorrhagic infarction, post-hemorrhagic hydrocephalus and periventricular leukomalacia. Long-term neurodevelopmental outcomes depend on the severity of the hemorrhage. High-grade IVH (grade III or IV) is associated with a 50% risk for cerebral palsy and significant intellectual disability. Such disabilities have devastating and lifelong impact on affected children, their families and society. In more than 90% of the cases, IVH in ELGA infants occurs during the first three postnatal days. The major risk factor for IVH is the gestational age of the infant with greater immaturity being associated with the highest risk. The degree of prematurity of the infant relates to the immaturity of the vascular bed within the germinal matrix as well as challenges in the regulation of the cerebrovascular circulation. Specifically, increases, decreases and significant fluctuations in cerebral blood flow (CBF) have been shown to play important pathogenic roles in IVH. These CBF instabilities have been related to the mechanics of ventilation as well as to the severity of the infant's illness, with contributing factors of hypercarbia, hypovolemia, hypotension, restlessness, patent ductus arteriosus, and relatively high inspired oxygen concentrations. Another major contributing factor to CBF instabilities is the pressure-passive cerebral circulatory state in the unstable ELGA infants. To prevent such deleterious consequences on the developing brain of preterm infants, optimal therapeutic strategies that maintain both cardiopulmonary function and cerebrovascular stability need to be developed. The major obstacle impeding effective brain-oriented neonatal intensive care is the lack of a relevant bedside continuous monitor of cerebral blood flow.

Near-infrared spectroscopy (NIRS) is a non-invasive, non-ionizing method for monitoring and imaging of brain hemodynamics. Commercially available, FDA-approved NIRS systems provide hemoglobin concentration changes and relative hemoglobin oxygen saturation (rSO2) as a surrogate for cerebral perfusion and oxygen consumption. However currently there are no commercially available monitors, which can directly assess cerebral perfusion and oxygen consumption in preterm infants. We are investigating the possibility of using a novel NIRS optical method to quantify cerebral perfusion, continuously, at the bedside in the NICU preterm population. We believe the use of Diffuse Correlation Spectroscopy (DCS) as a stand-alone and in combination with frequency-domain (FD) or continuous wave (CW) NIRS will offer more robust diagnostic capabilities by directly quantifying cerebral blood flow (CBF), and cerebral oxygen metabolism (CMRO2). Our preliminary efforts in animals and humans with this optical device show the potential of the technique.

Measurement Protocol Summary:

1. Start measurements within 48 hours of life, monitor for up to 72 hrs.
2. Up to 2 optical sensors will be attached with hydrogel, and affixed using either an infant hat headband or medical grade tapes.
3. Attached optical sensors will be adjusted every few hours to ensure that there is no disruption to skin integrity. Skin integrity will be assessed every time the optical sensors are moved and discussed with research nurse or nurse caring for infant
4. When available physiological parameters including heart rate, blood pressure, transcutaneous CO2 (TcCO2), cerebral oximetry and other systemic parameters from the bedside monitors will be collected to be compared to the optical data.
5. A research pulse oximeter will be attached to the baby to record arterial saturation (SpO2).
6. A small accelerometer will be attached to the optical sensor next to the optical sensor to record baby head motion.
7. In a subgroup of babies we will also monitor enrolled infants with aEEG and FDNIRS. The aEEG leads are currently used in NICU for clinical care and the FDNIRS handheld probe is currently used in research. Depending on availability of the FDNIRS device and access to the infant, every 4 to 12 hrs, we will perform FDNIRS measurements by using a hand-held optical sensor.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maria A Franceschini, PhD; Phone Number: 617-726-4024; Email: mfranceschini@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Mohamed El-Dib, MD; Phone Number: 617-732-6902; Email: mel-dib@bwh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 days (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• Premature infants born at <29 weeks GA and <48 hrs of age.
• No contraindication to DCS optical sensor placement on the scalp
• No major congenital anomalies,
• No Complex cyanotic congenital cardiac disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ELGA group; *Less than 29 weeks Gestational Age (GA) preemies (100) DCS monitoring will be performed for up to 72 hours starting within 2 days after birth. In a subgroup of infants, we will also perform additional measurements with aEEG and FDNIRS. At a second stage we will add Transcranial Doppler Ultrasound (TCD)

Device: Diffuse Correlation Spectroscopy (DCS); Diffuse correlation spectroscopy uses light in the near infrared spectral region to quantify non-invasively cerebral blood flow. The DCS device will be use to monitor blood flow changes over time in all ELGA enrolled babies; Device: Amplitude Integrated Electroencephalography (aEEG); Amplitude Integrated Electroencephalography like EEG it is used clinically to monitor brain function in intensive care settings over longer periods of time. aEEG data will be correlated with CBF variation over time

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Test the feasibility of DCS CBF continuous measures in ELGA newborn	Test the feasibility of DCS monitoring of cerebral perfusion in extremely premature infants during the first few days of life.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation with intraventricular hemorrhage	To assess if cerebral blood flow disturbances measured with DCS correlate with incidence of intraventricular hemorrhage.	5 years
Correlation with clinical outcome	Correlate the DCS findings with clinical outcome at hospital discharge	5 years

Collaborators and Investigators

• Sponsor: Maria Angela Franceschini
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Terrie E Inder, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2019
• Primary Completion (Anticipated): May 31, 2023
• Study Completion (Anticipated): May 31, 2023

Study Registration Dates

• First Submitted: February 24, 2020
• First Submitted That Met QC Criteria: April 26, 2020
• First Posted (Actual): April 29, 2020

Study Record Updates

• Last Update Posted (Actual): April 29, 2020
• Last Update Submitted That Met QC Criteria: April 26, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Cerebral Blood Flow; Near-Infrared Spectroscopy; Diffuse Correlation Spectroscopy
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Body Weight; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Intracranial Hemorrhages; Hemorrhage; Premature Birth; Birth Weight; Cerebral Hemorrhage
• Other Study ID Numbers: 2014P002022; 1R01HD091067-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: upon request and at study completion
• IPD Sharing Access Criteria: file share
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No