Cerebral Physiology of NOWS (NIRS for NOWS)

May 26, 2026 updated by: Anna Thomas, Indiana University

Early Detection of Neonatal Opioid Withdrawal Syndrome Using a Novel Cerebral Monitor.

This study will use a new device to measure blood flow and oxygen levels in the brains of newborn infants who have had exposure to opioid medications in the womb, compared to newborns who have not had any exposure.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The investigators propose to use a novel optical-based device that combines two advanced NIRS techniques, frequency-domain NIRS (FD-NIRS) and diffuse correlation spectroscopy (DCS), to quantify regional cerebral oxygenation (SO2), cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2) in neonates with similar ease of use as commercial NIRS devices, offering a more comprehensive metabolic profile of early brain function. Our technology has been validated in infant populations, demonstrating robust biomarkers of brain health and function in both healthy and at-risk infants. A pilot study at Riley Hospital for Children has already revealed differences in absolute cerebral oxygenation (SO2) as measured by quantitative FD-NIRS instrumentation in a small sample of neonates with POE and age-matched controls on the first 24 hours of life.

The investigators hypothesize that infants who develop severe NOWS will exhibit early measurable alterations in cerebral oxygenation, blood flow, and/or metabolism in the early postnatal period. Thus, the investigators propose to acquire FD-NIRS/DCS measurements in infants with prenatal opioid exposure (POE) in their first days of life.

Aim 1: Determine early trajectories of cerebral physiology in neonates with POE using a non-invasive FD-NIRS/DCS device.

Aim 2: Investigate early associations between FD-NIRS/DCS measurements and short-term clinical outcomes in neonates with POE.

Aim 3: Monitor changes in cerebral physiology during pharmacologic treatment in infants with severe NOWS.

Study Type

Interventional

Enrollment (Estimated)

46

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Hannah Rykovich, RN
  • Phone Number: 3174740725
  • Email: hsrakow@iu.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

Infants with prenatal opioid exposure:

  • Term born or near-term born (> 36w) infants
  • Birth weight > 2 Kg
  • History of prenatal opioid exposure

Control infants:

  • Term born or near-term born (> 36w) infants
  • Birth weight > 2 Kg

Mothers of infants with prenatal opioid exposure:

  • greater or equal to 19 years of age
  • Use of opioid substances during pregnancy - Defined as pregnant women who 1) are clinically diagnosed as having an opioid use disorder and are on methadone or buprenorphine maintenance program or 2) have a urine drug test positive for prescribed or illicit opioids

Mothers of control infants:

  • greater than or equal to 19 years of age

Exclusion Criteria:

Infants with prenatal opioid exposure:

  • APGAR score at 5 min < 7
  • Any major congenital malformations or genetic syndromes
  • Need for positive pressure ventilation in the delivery room

Control infants:

  • APGAR score at 5 min < 7
  • Any major congenital malformations or genetic syndromes
  • Need for positive pressure ventilation in the delivery room
  • Any history of prenatal opioid exposure

Mothers of infants with prenatal opioid exposure:

  • Major maternal illness during pregnancy or delivery that could impact infant cerebral perfusion as deemed by the study investigators (e.g. uterine rupture or preeclampsia)

Mothers of control infants:

  • Major maternal illness during pregnancy or delivery that could impact infant cerebral perfusion as deemed by the study investigators (e.g. uterine rupture or preeclampsia)
  • Tobacco, SSRI or any opioid use during pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Prenatal opioid exposure (POE)
A total of 20 newborns with prenatal opioid exposure will have daily bedside FD-NIRS/DCS measurements of cerebral oxygen saturation (SO₂), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen consumption (CMRO₂).
Device: FD-NIRS and DCS
The investigators will use a novel optical-based device that combines two advanced NIRS techniques, frequency-domain NIRS (FD-NIRS) and diffuse correlation spectroscopy (DCS), to quantify regional cerebral oxygenation (SO2), cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2).
Experimental: Healthy control
A total of 20 healthy age-matched newborns will have daily bedside FD-NIRS/DCS measurements of cerebral oxygen saturation (SO₂), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen consumption (CMRO₂).
Device: FD-NIRS and DCS
The investigators will use a novel optical-based device that combines two advanced NIRS techniques, frequency-domain NIRS (FD-NIRS) and diffuse correlation spectroscopy (DCS), to quantify regional cerebral oxygenation (SO2), cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2).
Experimental: Pharmacologic Treatment
A group of 6 newborns with POE who are treated pharmacologically for severe neonatal opioid withdrawal syndrome will have daily bedside FD-NIRS/DCS measurements of cerebral oxygen saturation (SO₂), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen consumption (CMRO₂).
Device: FD-NIRS and DCS
The investigators will use a novel optical-based device that combines two advanced NIRS techniques, frequency-domain NIRS (FD-NIRS) and diffuse correlation spectroscopy (DCS), to quantify regional cerebral oxygenation (SO2), cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Daily measurements of cerebral oxygenation
Time Frame: From birth up to 5 days of life for the control and POE infants; from birth to study completion, an average of 14 days, for pharmacologically-treated infants

For aims 1 and 2, daily measurements of cerebral oxygenation (%) will be obtained using the bedside optical device in infants with POE and age-matched controls during the first five days after birth.

For aim 3, longitudinal measurements of cerebral oxygenation (%) will be obtained using the bedside optical device in infants with severe NOWS undergoing pharmacological treatment.
From birth up to 5 days of life for the control and POE infants; from birth to study completion, an average of 14 days, for pharmacologically-treated infants
Daily measurements of cerebral blood flow
Time Frame: From birth up to 5 days of life for the control and POE infants; from birth to study completion, an average of 14 days, for pharmacologically-treated infants

For aims 1 and 2, daily measurements of cerebral blood flow (cm^2/s) will be obtained using the bedside optical device in infants with POE and age-matched controls during the first five days after birth.

For aim 3, longitudinal measurements of cerebral blood flow (cm^2/s) will be obtained using the bedside optical device in infants with severe NOWS undergoing pharmacological treatment.
From birth up to 5 days of life for the control and POE infants; from birth to study completion, an average of 14 days, for pharmacologically-treated infants
Daily measurements of cerebral oxygen consumption
Time Frame: From birth up to 5 days of life for the control and POE infants; from birth to study completion, an average of 14 days, for pharmacologically-treated infants

For aims 1 and 2, daily measurements of cerebral oxygen consumption (mol/dl.cm^2/s) will be obtained using the bedside optical device in infants with POE and age-matched controls during the first five days after birth.

For aim 3, longitudinal measurements of cerebral oxygen consumption (mol/dl.cm^2/s) will be obtained using the bedside optical device in infants with severe NOWS undergoing pharmacological treatment.
From birth up to 5 days of life for the control and POE infants; from birth to study completion, an average of 14 days, for pharmacologically-treated infants

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Severity of neonatal opioid withdrawal
Time Frame: From birth to study completion, an average of 14 days.
The numerical modified Finnegan score (FNAST) or the Eat, Sleep, Console (ESC) score, depending on which tool is used for scoring at the site, will be recorded closest in proximity to measurements of cerebral physiology. The FNAST is a long-standing scoring tool that gives a numerical score as a measure of severity of withdrawal, with higher scores being more severe, up to a maximum of 24. The ESC score is a newer scoring tool that is not numerical but rather normal or abnormal in 3 categories of symptoms. Having an abnormal score for any of the 3 categories may qualify for intervention.
From birth to study completion, an average of 14 days.
Length of hospital stay
Time Frame: Birth to hospital discharge, an average of 14 days.
Length of hospital stay in days.
Birth to hospital discharge, an average of 14 days.
Need for postnatal pharmacologic treatment
Time Frame: From birth to 7 days of age.
Whether the infant requires pharmacologic treatment with an opioid to treat severe neonatal opioid withdrawal.
From birth to 7 days of age.
Total postnatal opioid exposure
Time Frame: Treatment initiation to completion, an average of 14 days.
Total cumulative amount of morphine needed to treat neonatal opioid withdrawal in mg/kg (based on birth weight)
Treatment initiation to completion, an average of 14 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Indiana University

Collaborators

National Institute on Drug Abuse (NIDA)
Indiana Clinical and Translational Sciences Institute

Investigators

  • Principal Investigator: Anna Thomas, MD, Indiana University
  • Principal Investigator: Silvina Ferradal, PhD, Indiana University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

April 1, 2027

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

May 11, 2026

First Submitted That Met QC Criteria

May 26, 2026

First Posted (Actual)

May 28, 2026

Study Record Updates

Last Update Posted (Actual)

May 28, 2026

Last Update Submitted That Met QC Criteria

May 26, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 28208
  • 1R21DA063767-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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