Multimodal Fetal and Placental Imaging and Biomarkers of Clinical Outcomes in Opioid Use Disorder

Pregnancy Related Clinical Trial

Official title:

Multimodal Fetal and Placental Imaging and Biomarkers of Clinical Outcomes in Opioid Use Disorder

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06415994
• Other study ID #: RADY-IIR-19751
• Secondary ID: R01DA059321
• Status: Enrolling by invitation
• Start date: February 13, 2024
• Est. completion date: December 1, 2029

Study information

• Verified date: May 2024
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this observational study is to learn about the long term effects of prenatal opioid exposure. The main objectives are:

• Long term goal: to improve the safety and efficacy of maternal Opioid Use Disorder (OUD) and eliminate neonatal opioid withdrawal syndrome (NOWS) and poor childhood neurodevelopment.

• To characterize prenatal opioid exposure (POE) related placental and fetal brain structural and functional disruptions using longitudinal placenta-fetal brain magnetic resonance imaging (MRI) and determine proteomic, genomic, and epigenetic signatures of NOWS and poor infant neurodevelopment.

In this study participants will:

• Receive two placental-fetal MRIs, one during second trimester and one in third trimester.

• Answer surveys relating to their medical and social history.

• Have blood drawn during pregnancy and delivery.

• Child development follow up: answer surveys on their child's development milestones and at one year of life they will undergo a development assessment.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 250
• Est. completion date: December 1, 2029
• Est. primary completion date: December 1, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 100 Years

Eligibility

Pregnant women with opioid use disorder

Inclusion Criteria:

• Age >18 years

• Currently taking buprenorphine or methadone for OUD and are enrolled in a prenatal opioid maintenance program

• Singleton Pregnancy

• Planned delivery at Indiana University or University of Pittsburgh study sites

Exclusion Criteria:

• Serious maternal medical illness as deemed by study physician investigators that would make it challenging to comply with study procedures

• Known or suspected major fetal/ neonatal congenital abnormalities

• HIV or AIDS

Infants with prenatal opioid exposure:

Inclusion:

1. Prenatal buprenorphine or methadone exposure

2. Born to mother enrolled in Opioid Use Disorder arm of study

Exclusion:

Major congenital anomalies or genetic syndromes affecting neurodevelopment

Control Pregnant Women:

Inclusion:

1. Women >18 Years of age

2. Healthy singleton pregnancy

3. Planned delivery at Indiana University or University of Pittsburgh study sites

Exclusion:

1. Serious maternal medical illness as deemed by study physician investigators that would make it challenging to comply with study procedures

2. HIV or AIDS

3. Known or suspected major fetal congenital abnormalities

4. Any history of opioid misuse before or during pregnancy-per self-report and clinical notes.

Control infants:

Inclusion:

Born to control pregnant mother enrolled in study

Exclusion:

Any major congenital anomalies, genetic abnormalities, neurologic abnormalities, syndromes, or chronic medical conditions affecting neurodevelopment.

Related Conditions & MeSH terms

• Buprenorphine Dependence
• Methadone Dependence
• Opioid Use Disorder
• Opioid-Related Disorders
• Pregnancy Related
• Substance-Related Disorders

Intervention

Drug:
• Buprenorphine or Methadone Treatment
Pregnant mothers must be taking Buprenorphine or Methadone

Diagnostic Test:
• Fetal and Placental MRI
Two MRIs : Second Trimester Third Trimester

Behavioral:
• Child Developmental Assessment
At 1 year of life child will receive a developmental assessment
• Questionnaires
Participants will answer questionnaires on their medical history, pregnancy, substance use, and after birth: their child's development

Other:
• Blood and Placental Samples
At each MRI visit a blood sample will be collected for substances, DNA, RNA, epigenetics, and placental biomarkers. At delivery: A sample of placenta will be collected for RNA, DNA, and epigenetic analysis.

Locations

Country	Name	City	State
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	University of Pittsburg	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Indiana University	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Alterations in fetal brain volume	Comparing changes in fetal brain volume using MRI between babies who have had prenatal opioid exposure (POE) and controls	Between 20 weeks gestation and delivery
Primary	Differences in placenta signal	Comparing differences in placenta signal using MRI between the POE group and controls	Between 20 weeks gestation and delivery
Secondary	Placental epigenetic changes related to POE	Compare placental DNA methylation in POE group and control group	Between 20 weeks gestation and delivery
Secondary	Placental dysfunction biomarkers related to POE	Compare concentrations of blood proteins in POE group vs controls	Between 20 weeks gestation and delivery
Secondary	Neonatal Opioid Withdrawal Syndrome (NOWS) severity	Measuring NOWs severity in the POE group using eat sleep console scores	After birth through one year of life
Secondary	Length of Hospital Stay	Measuring NOWs severity in the POE group using length of hospital stay	After birth through one year of life
Secondary	Ages and Stages Questionnaire Scores during infancy	Comparing neurodevelopment of POE group and controls using the ages and stages questionnaire at multiple time points in baby's first year of life. This questionnaire assesses infants developmental level. Scores can identify whether child is below cutoff and needs professional intervention, close to cutoff and requires more developmental support and learning, or above cutoff and on track.	After birth through one year of life
Secondary	Neurocognitive and behavioral development assessment (Bayley-4) at one year of age	Comparing neurodevelopment of POE group and controls using the Bayley's 4 assessment at one year of age. This assessment is administered by professionals to identify development delays in children.	After birth through one year of life