## Protocol Section
### Identification Module
**NCT ID:** NCT06415994

**Brief Title:** Multimodal Fetal and Placental Imaging and Biomarkers of Clinical Outcomes in Opioid Use Disorder

**Official Title:** Multimodal Fetal and Placental Imaging and Biomarkers of Clinical Outcomes in Opioid Use Disorder

#### Organization Study ID Info
**ID:** RADY-IIR-19751
#### Organization
**Class:** OTHER
**Full Name:** Indiana University
#### Secondary ID Infos
**ID:** R01DA059321
**Link:** https://reporter.nih.gov/quickSearch/R01DA059321
**Type:** NIH
### Status Module
#### Completion Date
**Date:** 2029-12-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-14

**Overall Status:** ENROLLING_BY_INVITATION

#### Primary Completion Date
**Date:** 2028-12-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-02-13

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-03-04
**Study First Submit QC Date:** 2024-05-14
### Sponsor Collaborators Module

#### Collaborators

**Class:** NIH

**Name:** National Institute on Drug Abuse (NIDA)

#### Lead Sponsor

**Class:** OTHER

**Name:** Indiana University

#### Responsible Party

**Investigator Affiliation:** Indiana University

**Investigator Full Name:** Rupa Radhakrishnan

**Investigator Title:** Associate Professor of Radiology & Imaging Sciences

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief 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.

### Conditions Module

**Conditions:**

- Opioid Use Disorder

- Substance-Related Disorders

- Pregnancy Related

- Narcotic-Related Disorders

- Buprenorphine Dependence

- Methadone Dependence

**Keywords:**

- Pregnant with Opioid Use Disorder

- Opioid Use Disorder

- Subutex

- Buprenorphine

- Pregnant taking buprenorphine/subutex

### Design Module

#### Bio Spec

**Description:** Blood samples will be collected at MRI visits for substances, DNA, RNA and epigenetic analysis.

Placental sample: A sample of the placenta will be collected during delivery for analysis DNA, RNA and epigenetic analysis.

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 250

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 150 pregnant mothers with opioid use disorder who are on buprenorphine or methadone treatment

**Intervention Names:**

- Drug: Buprenorphine or Methadone Treatment

- Diagnostic Test: Fetal and Placental MRI

- Behavioral: Child Developmental Assessment

- Behavioral: Questionnaires

- Other: Blood and Placental Samples

**Label:** Pregnant Mothers with Opioid Use Disorder

#### Arm Group 2

**Description:** 100 pregnant mother who to not have a history of opioid use disorder

**Intervention Names:**

- Diagnostic Test: Fetal and Placental MRI

- Behavioral: Child Developmental Assessment

- Behavioral: Questionnaires

- Other: Blood and Placental Samples

**Label:** Pregnant Mothers

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Pregnant Mothers with Opioid Use Disorder

**Description:** Pregnant mothers must be taking Buprenorphine or Methadone

**Name:** Buprenorphine or Methadone Treatment

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Pregnant Mothers

- Pregnant Mothers with Opioid Use Disorder

**Description:** Two MRIs :

* Second Trimester
* Third Trimester

**Name:** Fetal and Placental MRI

**Type:** DIAGNOSTIC_TEST

#### Intervention 3

**Arm Group Labels:**

- Pregnant Mothers

- Pregnant Mothers with Opioid Use Disorder

**Description:** At 1 year of life child will receive a developmental assessment

**Name:** Child Developmental Assessment

**Type:** BEHAVIORAL

#### Intervention 4

**Arm Group Labels:**

- Pregnant Mothers

- Pregnant Mothers with Opioid Use Disorder

**Description:** Participants will answer questionnaires on their medical history, pregnancy, substance use, and after birth: their child's development

**Name:** Questionnaires

**Type:** BEHAVIORAL

#### Intervention 5

**Arm Group Labels:**

- Pregnant Mothers

- Pregnant Mothers with Opioid Use Disorder

**Description:** 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.

**Name:** Blood and Placental Samples

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** Comparing changes in fetal brain volume using MRI between babies who have had prenatal opioid exposure (POE) and controls

**Measure:** Alterations in fetal brain volume

**Time Frame:** Between 20 weeks gestation and delivery

**Description:** Comparing differences in placenta signal using MRI between the POE group and controls

**Measure:** Differences in placenta signal

**Time Frame:** Between 20 weeks gestation and delivery

#### Secondary Outcomes

**Description:** Compare placental DNA methylation in POE group and control group

**Measure:** Placental epigenetic changes related to POE

**Time Frame:** Between 20 weeks gestation and delivery

**Description:** Compare concentrations of blood proteins in POE group vs controls

**Measure:** Placental dysfunction biomarkers related to POE

**Time Frame:** Between 20 weeks gestation and delivery

**Description:** Measuring NOWs severity in the POE group using eat sleep console scores

**Measure:** Neonatal Opioid Withdrawal Syndrome (NOWS) severity

**Time Frame:** After birth through one year of life

**Description:** Measuring NOWs severity in the POE group using length of hospital stay

**Measure:** Length of Hospital Stay

**Time Frame:** After birth through one year of life

**Description:** 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.

**Measure:** Ages and Stages Questionnaire Scores during infancy

**Time Frame:** After birth through one year of life

**Description:** 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.

**Measure:** Neurocognitive and behavioral development assessment (Bayley-4) at one year of age

**Time Frame:** After birth through one year of life

### Eligibility Module

**Eligibility Criteria:** 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.

**Healthy Volunteers:** True

**Maximum Age:** 100 Years

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** FEMALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Any woman of the age of 18 or older that is having a single pregnancy, and currently taking buprenorphine or methadone for opioid use disorder.

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Indianapolis

**Country:** United States

**Facility:** Riley Hospital for Children

**State:** Indiana

**Zip:** 46202

**Location 2:**

**City:** Pittsburgh

**Country:** United States

**Facility:** University of Pittsburg

**State:** Pennsylvania

**Zip:** 15260

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000064419

- Term: Chemically-Induced Disorders

- ID: D000001523

- Term: Mental Disorders

### Condition Browse Module - Browse Branches

- Abbrev: BC25

- Name: Substance Related Disorders

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M21837

- Name: Substance-Related Disorders

- Relevance: HIGH

- As Found: Substance-Related Disorders

- ID: M2057

- Name: Narcotic-Related Disorders

- Relevance: HIGH

- As Found: Narcotic-Related Disorders

- ID: M12244

- Name: Opioid-Related Disorders

- Relevance: HIGH

- As Found: Opioid Use Disorder

- ID: M30302

- Name: Chemically-Induced Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4815

- Name: Mental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14473

- Name: Psychotic Disorders

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000009293

- Term: Opioid-Related Disorders

- ID: D000019966

- Term: Substance-Related Disorders

- ID: D000079524

- Term: Narcotic-Related Disorders

### Intervention Browse Module - Ancestors

- ID: D000000701

- Term: Analgesics, Opioid

- ID: D000009294

- Term: Narcotics

- ID: D000002492

- Term: Central Nervous System Depressants

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000000700

- Term: Analgesics

- ID: D000018689

- Term: Sensory System Agents

- ID: D000018373

- Term: Peripheral Nervous System Agents

- ID: D000009292

- Term: Narcotic Antagonists

- ID: D000000996

- Term: Antitussive Agents

- ID: D000019141

- Term: Respiratory System Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Analg

- Name: Analgesics

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

- Abbrev: NarcAntag

- Name: Narcotic Antagonists

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: AnTuAg

- Name: Antitussive Agents

- Abbrev: Resp

- Name: Respiratory System Agents

- Abbrev: AnObAg

- Name: Anti-Obesity Agents

- Abbrev: VaCoAg

- Name: Vasoconstrictor Agents

### Intervention Browse Module - Browse Leaves

- ID: M5317

- Name: Buprenorphine

- Relevance: HIGH

- As Found: Class

- ID: M11671

- Name: Methadone

- Relevance: HIGH

- As Found: Before surgery

- ID: M4033

- Name: Analgesics, Opioid

- Relevance: LOW

- As Found: Unknown

- ID: M4032

- Name: Analgesics

- Relevance: LOW

- As Found: Unknown

- ID: M12245

- Name: Narcotics

- Relevance: LOW

- As Found: Unknown

- ID: M12243

- Name: Narcotic Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M13570

- Name: Phenylpropanolamine

- Relevance: LOW

- As Found: Unknown

- ID: M9238

- Name: Guaifenesin

- Relevance: LOW

- As Found: Unknown

- ID: M186319

- Name: Chlorpheniramine, phenylpropanolamine drug combination

- Relevance: LOW

- As Found: Unknown

- ID: M4312

- Name: Antitussive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M21137

- Name: Respiratory System Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000002047

- Term: Buprenorphine

- ID: D000008691

- Term: Methadone

### Misc Info Module

- Version Holder: 2024-05-31
