ACT NOW Longitudinal Study: Outcomes of Babies With Opioid Exposure Study (OBOE)

• ClinicalTrials.gov Identifier: NCT04149509
• Recruitment Status: Recruiting
• First Posted: November 4, 2019
• Last Update Posted: February 1, 2023
• Sponsor: Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Program
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Program

Tracking Information

• First Submitted Date: October 24, 2019
• First Posted Date: November 4, 2019
• Last Update Posted Date: February 1, 2023
• Actual Study Start Date: August 19, 2020
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 31, 2019)

• Primary outcome related to brain development: White Matter Volume [ Time Frame: Birth to 22-24 months of age ]
  Volumetric analysis will be done with the white matter volume obtained from each of the MRI images collected from birth until 22-24 months of age. The differences between the exposed and non-exposed groups will be calculated.
• Primary outcome related to brain development: Cortical Gray Matter Volume [ Time Frame: Birth to 22-24 months of age ]
  Volumetric analysis will be done with the cortical gray matter volume obtained from each of the MRI images collected from birth until 22-24 months of age. The differences between the exposed and non-exposed groups will be calculated.
• Primary outcome related to brain development: Deep Gray Matter Volume [ Time Frame: Birth to 22-24 months of age ]
  Volumetric analysis will be done with the deep gray matter volume obtained from each of the MRI images collected from birth until 22-24 months of age. The differences between the exposed and non-exposed groups will be calculated.
• Primary outcome related to brain development: Lateral Ventricle Volume [ Time Frame: Birth to 22-24 months of age ]
  Volumetric analysis will be done with the lateral ventricle volume obtained from each of the MRI images collected from birth until 22-24 months of age. The differences between the exposed and non-exposed groups will be calculated.
• Primary outcome related to brain development: External cerebrospinal fluid [ Time Frame: Birth to 22-24 months of age ]
  Volumetric analysis will be done with the external cerebrospinal fluid volume obtained from each of the MRI images collected from birth until 22-24 months of age. The differences between the exposed and non-exposed groups will be calculated.
• Primary outcome related to behavioral and development: Bayley Scales of Infant Development [ Time Frame: 22-24 months of age ]
  The Bayley Scales of Infant Development is considered the gold standard assessment of early child development and includes cognitive, language, fine motor, and gross motor subscales. Subscale scores each range from 1 - 19, with higher scores indicating higher performance.
• Primary outcome related to behavioral and development: Spot Vision Screener [ Time Frame: 22-24 months of age ]
  The vision screener and auto-refractor detects amblyopia risk factors such as myopia, hyperopia, astigmatism, anisometropia, gaze, and anisocoria. Results are reported as "all measurements in range-pass" or "complete eye exam recommended-fail" based on manufacturer criteria for age. If the screen recommends a complete eye exam, the reason for failure (of the 6 factors listed above) and affected eye(s) will be recorded.
• Primary outcome related to behavioral and development: BITSEA [ Time Frame: 22-24 months of age ]
  Brief Infant-Toddler Social and Emotional Assessment (BITSEA) is a 42 item tool that is useful for identifying social-emotional problems and/or deficits in children. BITSEA includes the following subscales: Competence (11 Items, min score:0, max score:22), problem behaviors--dysregulation (8 items, min score:0, max score:16) , externalizing (6 items, min score:0, max score:12), internalizing (8 items, min score:0, max score:16), Autism Spectrum Disorder (17 Items, min score:0, max score:34), and Red Flags (14 items, min score:0, max score:28).The questions overlap and the problem subscale is a combination of dysregulation, externalizing, and internalizing. Higher problem scores indicate greater levels of social-emotional/behavioral problems. Lower Competence scores indicate possible delay/deficit.

• Original Primary Outcome Measures: Same as current
• 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: ACT NOW Longitudinal Study: Outcomes of Babies With Opioid Exposure Study
• Official Title: ACT NOW Longitudinal Study: Outcomes of Babies With Opioid Exposure Study
• Brief Summary: The objective of this longitudinal cohort study is to quantify the effects of antenatal opioid exposure on the trajectory of brain development over the first 2 years of life, examine associations with developmental and neurobehavioral outcomes, and explore how specific factors (differing antenatal and postnatal exposures, severity of neonatal opioid withdrawal, maternal stress/depression/parenting) modify these effects
• Detailed Description: This objective of this longitudinal cohort study is to prospectively examine the medical, neuroanatomical, neurodevelopmental, behavioral, and social/family/home outcomes of infants who were exposed to opioids in utero. Match control infants will be recruited into the study and based on birth hospital and birth month of the exposed infants. The study will quantify the effects of antenatal opioid exposure on the trajectory of brain development over the first 2 years of life, examine associations with developmental and neurobehavioral outcomes, and explore how specific factors (differing antenatal and postnatal exposures, severity of neonatal opioid withdrawal, maternal stress/depression/parenting) modify these effects. The investigators hypothesize that neural connectivity and neuroanatomical volumes are altered by antenatal opioid exposure and that the magnitude of these alterations correlates with developmental and behavioral outcomes. Further, maternal and environmental factors interact with antenatal opioid exposure to influence the trajectories of connectivity, development, and behavior over the first 2 years of life.
• Study Type: Observational
• Study Design: Observational Model: Other; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Infants will be prescreened at participating birth hospitals using the inclusion and exclusion criteria listed below.
• Condition: Neonatal Opioid Withdrawal Syndrome
• Intervention: Not Provided

Study Groups/Cohorts

• Exposed
  Infants born ≥ 37 weeks gestation with second or third trimester opioid exposure as determined by maternal urine toxicology screen at delivery; maternal history; and/or infant urine, meconium, or umbilical cord toxicology screen.
• Unexposed - Controls
  Infants born ≥ 37 weeks gestation with no antenatal drug exposure as determined by maternal urine toxicology screen at delivery and/or maternal history. We will match control infants to exposed infants based on Clinical Site and up to 60 days after the date of birth of the exposed infant , recruiting 1 control for every other exposed infant at each site.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 30, 2021): 300
• Original Estimated Enrollment (submitted: October 31, 2019): 275
• Estimated Study Completion Date: July 2023
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Exposed infants: Born ≥37 weeks gestation with second or third trimester opioid exposure
• Control infants: Born ≥37 weeks gestation with no antenatal drug exposure

Exclusion Criteria:

1. Infants with known chromosomal or congenital anomalies potentially affecting the central nervous system
2. Apgar score at 5 minutes of <5
3. Any requirement for positive pressure ventilation in the NICU
4. Inability to return for outpatient MRI and/or follow-up
5. IUGR <3rd percentile
6. Heavy alcohol use during pregnancy (8+ drinks per week).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 1 Month (Child)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Carla Bann, PhD; 919-485-2773; cmb@rti.org

Contact: Jamie Newman, PhD; 9194855719

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04149509
• Other Study ID Numbers: ACTNOW-03; 1PL1HD101059-01 ( U.S. NIH Grant/Contract ); RL1HD104251 ( U.S. NIH Grant/Contract ); RL1HD104252 ( U.S. NIH Grant/Contract ); RL1HD104253 ( U.S. NIH Grant/Contract ); RL1HD104254 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

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

• Plan to Share IPD: Yes
• Plan Description: Plan to Share IPD

• Current Responsible Party: Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Program
• Original Responsible Party: Same as current
• Current Study Sponsor: Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Program
• Original Study Sponsor: Same as current
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Study Director: Carla Bann, PhD; RTI International

• PRS Account: Advancing Clinical Trials in Neonatal Opioid Withdrawal (ACT NOW) Program
• Verification Date: January 2023