NIRS Monitoring in Premature Infants

• ClinicalTrials.gov Identifier: NCT02601339
• Recruitment Status: Recruiting
• First Posted: November 10, 2015
• Last Update Posted: August 1, 2022
• Sponsor: Boston Children's Hospital
• Collaborators: Brigham and Women's Hospital; Beth Israel Deaconess Medical Center; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Pei-Yi Lin, Boston Children's Hospital

Tracking Information

• First Submitted Date: November 6, 2015
• First Posted Date: November 10, 2015
• Last Update Posted Date: August 1, 2022
• Actual Study Start Date: April 2015
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 25, 2018)

CMRO2 [ Time Frame: 0-2 years old ]

The primary outcomes are FDNIRS-DCS-measured CMRO2 trajectory.

Original Primary Outcome Measures (submitted: November 6, 2015)

FDNIRS-DCS [ Time Frame: 0-2 years old ]

FDNIRS-DCS measures cerebral blood flow, oxygen saturation and cerebral oxygen of metabolism noninvasively at the patient's bedside. Study "measurement" session will last between 20 and 60 minutes. For each visit, an FDNIRS-DCS monitor is softly placed in contact with the subject's head, which will not cause any discomfort to infants. Repeated measurements in the same location on the head and in different locations will be done. The monitor contains optical fibers (not electrical wires) that are connected to light sources and detectors. Using this monitor, a low-power red light is shined on the subject's skin. The light changes in the brain will be detected by sensitive detectors in which way CBF, CMRO2 and SO2 are then estimated.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: NIRS Monitoring in Premature Infants
• Official Title: Beside Monitor of Cerebral Metabolism in Premature Infants With Intraventricular Hemorrhage and Post-Hemorrhagic Hydrocephalus

Brief Summary

This study uses frequency domain near-infrared spectroscopy coupled with diffuse correlation spectroscopy (FDNIRS-DCS) technology for monitoring cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO2) at the bedside for newborns with germinal matrix-intraventricular hemorrhage (GM-IVH) and/or post-hemorrhagic hydrocephalus (PHH) in comparison to newborns with hydrocephalus of a different etiology (VC) and healthy controls (HC). We hypothesize that baseline cerebral metabolic dysfunction is a better biomarker for GM-IVH and PHH severity and response to PHH treatment.

This is a Boston Children's Hospital (BCH)-institutional review board(IRB) approved, multi-site study that includes collaboration with Brigham and Women's Hospital (BWH) and Beth Israel Deaconess Medical Center (BIDMC). Pei-Yi Lin receives funding from The National Institute of Health (NIH) to support the study and is the overall principal Investigator (PI) overseeing the study.

Detailed Description

Introduction and specific aims:

Germinal matrix-intraventricular hemorrhage (GM-IVH) occurs in 45% of extremely low birth weight (ELBW) premature infants, often leading to long-term neurodevelopmental impairments (NDI). Post-hemorrhagic hydrocephalus (PHH) is a common complication of GM-IVH and increases the risk of major NDI to 75-90%. Currently, the only bedside tool to assess for hemorrhage and monitor for secondary hydrocephalus is ultrasound. Although increasing ventricular size is currently used to determine need for intervention, measures based on cerebral physiology are needed to better determine the impact of the expanding ventricles on individual cerebral metabolism.

Our group has developed advanced FDNIRS-DCS technology for monitoring cerebral oxygen metabolism (CMRO2) in newborns at the bedside. We hypothesize that baseline and evoked cerebral metabolic dysfunctions are better biomarkers for GM-IVH and PHH severity and response to PHH treatment. To test our hypotheses, we will address the following specific aims:

Aim 1: Determine post-natal cerebral hemodynamics and oxygen metabolism trajectories in GM-IVH and PHH neonates with respect to normal controls and differences between PHH infants and infants affected by hydrocephalus due to other pathologies.

We hypothesize that:

1. Infants with GM-IVH have lower CBF and CMRO2 than healthy controls and the decrease is in proportion to the severity of GM-IVH. (GM-IVH vs HC)
2. Infants with PHH have lower CBF and CMRO2 than healthy controls. (PHH vs HC)
3. For infants who developed PHH, the decrease of CBF and CMRO2 is affected by both hemorrhages and the severity of hydrocephalus. (PHH vs VC)

Aim 2: Test the efficacy of cerebral hemodynamics and metabolism in detecting hydrocephalus treatment response in both PHH and VC groups.

We hypothesize that CBF and CMRO2 increase in response to treatment-associated improvements in hydrocephalus but remain depressed when response to treatment is inadequate.

Aim 3: Test the sensitivity of FDNIRS-DCS measured cerebral hemodynamics and oxygen metabolism in predicting developmental outcomes in infants with GM-IVH and PHH. We will assess neurodevelopmental outcomes in all enrolled infants at 5-7, 10-12, and 22-24 months corrected age and correlate with FDNIRS-DCS measurements of CBF and CMRO2, and related quantities with neurodevelopmental outcomes at approximately 5-7, 10-12, and 22-24 months corrected age.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: The subject population will include premature and full-term neonates that fit criteria for one of the GM-IVH, PHH, HC, or VC groups.

Condition

• Hemorrhage
• Premature Infants
• Newborn
• Hydrocephalus

Intervention

Procedure: ETV/CPC

endoscopic third ventriculostomy (ETV) combined with choroid plexus cauterization (CPC) is a surgical procedure to treat infant hydrocephalus

Study Groups/Cohorts

• GM-IVH
  Premature infants who developed germinal matrix-intraventricular hemorrhage. FDNIRS-DCS measures will be performed up to once a day if clinically feasible.
• Posthemorrhagic hydrocephalus (PHH)

  Premature infants with complications of hydrocephalus secondary to intraventricular hemorrhage and have the potential to receive endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) and/or ventriculoperitoneal (VP) shunting for clinical treatment.

  FDNIRS-DCS measures will be performed up to once a day if clinically feasible. Additional FDNIRS-DCS measures will be performed on the day of hydrocephalus treatment to monitor the treatment response if clinically feasible. These additional measures are limited to up to four times a day.

  Intervention: Procedure: ETV/CPC
• Healthy Control (HC)
  Premature infants without diagnosed brain injuries. FDNIRS-DCS measures will be performed up to once a day if clinically feasible.
• Ventriculomegaly Control (VC)

  Infants who have symptomatic hydrocephalus of any etiology except post-hemorrhagic etiology and have the potential to receive ETV/CPC and/or VP shunting for clinical treatment.

  FDNIRS-DCS measures will be performed up to once a day if clinically feasible. Additional FDNIRS-DCS measures will be performed on the day of hydrocephalus treatment to monitor the treatment response if clinically feasible. These additional measures are limited to up to four times a day.

  Intervention: Procedure: ETV/CPC

Publications *

• Fantini S. Frequency-domain multichannel optical detector for noninvasive tissue spectroscopy and oximetry. Optical Engineering 34(1):32, 1995.
• Boas DA, Campbell LE, Yodh AG. Scattering and Imaging with Diffusing Temporal Field Correlations. Phys Rev Lett. 1995 Aug 28;75(9):1855-1858. doi: 10.1103/PhysRevLett.75.1855. No abstract available.
• Wilson-Costello D, Friedman H, Minich N, Fanaroff AA, Hack M. Improved survival rates with increased neurodevelopmental disability for extremely low birth weight infants in the 1990s. Pediatrics. 2005 Apr;115(4):997-1003. doi: 10.1542/peds.2004-0221.
• Roche-Labarbe N, Carp SA, Surova A, Patel M, Boas DA, Grant PE, Franceschini MA. Noninvasive optical measures of CBV, StO(2), CBF index, and rCMRO(2) in human premature neonates' brains in the first six weeks of life. Hum Brain Mapp. 2010 Mar;31(3):341-52. doi: 10.1002/hbm.20868. Erratum In: Hum Brain Mapp. 2011 Jul;32(7):1179.
• Berghella V. Preterm Birth [Internet]. John Wiley & Sons; 2010. 1 p.
• Horbar JD, Carpenter JH, Badger GJ, Kenny MJ, Soll RF, Morrow KA, Buzas JS. Mortality and neonatal morbidity among infants 501 to 1500 grams from 2000 to 2009. Pediatrics. 2012 Jun;129(6):1019-26. doi: 10.1542/peds.2011-3028. Epub 2012 May 21.
• Bates D, Maechler M, Bolker B, Walker S, editors. me4: Linear mixed-effects models using Eigen and S4 [Internet]. [cited 2015 Jun 2].
• Volpe JJ. Neurology of the Newborn. Elsevier Health Sciences; 2008. 1 p.
• Volpe JJ. Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances. Lancet Neurol. 2009 Jan;8(1):110-24. doi: 10.1016/S1474-4422(08)70294-1.
• Del Bigio MR. Cell proliferation in human ganglionic eminence and suppression after prematurity-associated haemorrhage. Brain. 2011 May;134(Pt 5):1344-61. doi: 10.1093/brain/awr052. Epub 2011 Apr 7.
• Fantini S, Franceschini MA, Fishkin JB, Barbieri B, Gratton E. Quantitative determination of the absorption spectra of chromophores in strongly scattering media: a light-emitting-diode based technique. Appl Opt. 1994 Aug 1;33(22):5204-13. doi: 10.1364/AO.33.005204.
• Lin PY, Roche-Labarbe N, Dehaes M, Carp S, Fenoglio A, Barbieri B, Hagan K, Grant PE, Franceschini MA. Non-invasive optical measurement of cerebral metabolism and hemodynamics in infants. J Vis Exp. 2013 Mar 14;(73):e4379. doi: 10.3791/4379.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 16, 2018): 70
• Original Estimated Enrollment (submitted: November 6, 2015): 170
• Estimated Study Completion Date: December 2023
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

1. GM-IVH group:

   Inclusion criteria for GM-IVH group: born at gestational age (GA) 24-32 weeks; < 3 months old corrected-GA (cGA) at first measure or eligible for measurement within 12 weeks after the infant reaches 40 weeks post-menstrual age (PMA). Grade I-III IVH diagnosed by clinical cranial ultrasound or magnetic resonance imaging (MRI).

   Exclusion criteria for GM-IVH group: chromosomal abnormalities known at the time of enrollment; known or suspected metabolic disorder or neoplasm; critical congenital heart disease; congenital hydrocephalus; brain lesions that affect cerebral brain metabolism, other than GMH-IVH; central nervous system (CNS) infection.

2. PHH group:

   Inclusion criteria for PHH group: born at gestational age (GA) 24-37 weeks < 3 months old cGA at first measure or eligible for measurement within 12 weeks after the infant reaches 40 weeks age (PMA). PHH diagnosed by clinical cranial ultrasound or MRI.

   Exclusion criteria for PHH group: chromosomal abnormalities known at the time of enrollment; known or suspected metabolic disorder or neoplasm; critical congenital heart disease; congenital hydrocephalus; brain lesions that affect cerebral brain metabolism, other than IVH-PHH; CNS infection. Implanted devices or other devices that preclude the use of MRI.

3. HC group:

   Inclusion criteria for HC group: born at gestational age (GA) 24-32 weeks; < 3 months old cGA at first measure or eligible for measurement within 12 weeks after the infant reaches 40 weeks age (PMA); Apgar >7 at 5 min.

   Exclusion criteria for HC group: any clinical indication of brain injury or congenital brain malformation; chromosomal abnormality known at the time of enrollment; known or suspected metabolic disorder or neoplasm; critical congenital heart disease; CNS infection.

4. VC group:

Inclusion criteria for VC group: < 12 months old cGA at first measure or eligible for measurement within 1 year after the infant reaches 40 weeks age (PMA). Symptomatic hydrocephalus of any etiology or at high risk of developing hydrocephalus of any etiology, except post-hemorrhagic etiology; characterized by abnormal rate of head growth and full anterior fontanelle. Ventricular enlargement diagnosed by ultrasonography or MRI; no signs of IVH.

Exclusion criteria for VC group: known or suspected metabolic disorder or neoplasm; critical congenital heart disease; CNS infection. Implanted devices or other devices that preclude the use of MRI.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 0 Months to 12 Months (Child)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Pei-Yi Lin, PhD; ivy.lin@childrens.harvard.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02601339
• Other Study ID Numbers: 2014P001713; 1K99HD083512-01 ( U.S. NIH Grant/Contract ); P00014042 ( Other Identifier: Boston Children's Hospital )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pei-Yi Lin, Boston Children's Hospital
• Original Responsible Party: Pei-Yi Lin, Massachusetts General Hospital, Instructor
• Current Study Sponsor: Boston Children's Hospital
• Original Study Sponsor: Massachusetts General Hospital

Collaborators

• Brigham and Women's Hospital
• Beth Israel Deaconess Medical Center
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Pei-Yi Lin, PhD; Boston Children's Hospital

• PRS Account: Boston Children's Hospital
• Verification Date: July 2022