Genetic Testing for Neonatal Abstinence Syndrome

Overseen By Rhea E Sullivan, B.S.

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Milton S. Hershey Medical Center

Must be taking: Opioids

Disqualifiers: Preterm birth, Mechanical ventilation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how certain genetic markers (tiny molecules that help control cell functions) react to opioid withdrawal in newborns. Researchers are exploring whether these markers, including let-7a microRNA, microRNA-146a, and microRNA-192, can predict infants' responses to treatment and their future development. The study focuses on newborns exposed to opioids during pregnancy and born at or after 35 weeks of gestation. Participants should have had opioid exposure for at least a month before birth. The goal is to improve care for infants experiencing withdrawal. As an unphased study, this trial offers a unique opportunity to contribute to groundbreaking research that could enhance treatment for newborns.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications.

What prior data suggests that this protocol is safe for infants with neonatal abstinence syndrome?

Research has shown that certain tiny molecules in the body, called microRNAs, can react to opioid exposure. Researchers are studying some of these, like let-7a, miR-146a, and miR-192, to see if they can help manage neonatal abstinence syndrome (NAS), a condition affecting newborns. Although few direct studies have assessed the safety of these microRNAs for humans, their natural occurrence in the body suggests they might be safe. The research remains in the early stages, focusing on understanding how these microRNAs work and their potential benefits. While they seem promising, their safety and effectiveness for newborns are still under investigation. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the treatments for Neonatal Abstinence Syndrome (NAS) because they explore the role of specific microRNAs, such as let-7a, microRNA-146a, and microRNA-192 levels, which are different from traditional methods like medication and supportive care. Unlike current treatments that mainly focus on managing withdrawal symptoms with drugs like morphine or methadone, these microRNAs could provide a more targeted approach by influencing gene expression. This novel mechanism has the potential to offer new insights into the biological processes of NAS and lead to more effective and personalized interventions for affected infants.

What evidence suggests that this trial's treatments could be effective for neonatal abstinence syndrome?

Research has shown that certain tiny molecules in the body, called microRNAs—such as let-7a, miR-146a, and miR-192—are crucial for understanding neonatal abstinence syndrome (NAS). These molecules respond to opioid exposure and can help predict which babies might experience more severe withdrawal symptoms. This trial will study the levels of these microRNAs in infants exposed to in utero opiates. For instance, using these microRNAs together has demonstrated a diagnostic accuracy with a sensitivity of 73.7%. This suggests they might help doctors identify which babies need extra care. Such insights could eventually lead to better treatment and outcomes for infants affected by NAS. ^{2 4 6 7 8}

Who Is on the Research Team?

Steven D. Hicks, MD, PhD

Principal Investigator

Associate Professor of Pediatrics

Are You a Good Fit for This Trial?

This trial is for newborns born at or transferred to Penn State Hershey Medical Center within 48 hours of birth, who are over 35 weeks gestation and have been exposed to opioids in-utero for more than a month. Their mothers must have documented opioid use during pregnancy. Babies needing intensive respiratory support or with major congenital anomalies can't participate.

Inclusion Criteria

Neonates born at Penn State Hershey Medical Center or transferred at <48 hours after birth

Mothers with chronic in-utero opioid use during pregnancy (≥1 month of gestation)

My newborn was exposed to opioids in the womb for more than a month and is at least 35 weeks gestation.

Exclusion Criteria

Infant exposure to magnesium sulfate

<35 week gestation

Mothers and neonates without history of opioid exposure/dependence

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Initial Assessment

Buccal swab collected within 96 hours of life to measure salivary microRNA levels

1 week

1 visit (in-person)

Hospital Stay and Monitoring

Infants are monitored for withdrawal symptoms and maximum morphine concentration required for symptom control

Duration of hospital stay

Follow-up

Neurodevelopmental outcome scores measured at 6 months of age

6 months

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• let-7a microRNA level
• microRNA-146a level
• microRNA-192 level

Trial Overview The study is testing if certain microRNAs in the saliva (let-7a, miR-146a, miR-192) can predict treatment needs and outcomes for babies with Neonatal Opioid Withdrawal Syndrome by using a simple buccal swab test.

How Is the Trial Designed?

Group I: Infants exposed to in utero opiates Experimental Treatment 1 Intervention

Infants that meet IRB-approved inclusion/exclusion criteria.

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

In a study of 37 patients undergoing methamphetamine abstinence and 35 healthy controls, a significant reduction in the miRNA marker miR-137 was found in the circulating extracellular vesicles (cEVs) of abstinent patients, indicating its potential as a diagnostic marker for methamphetamine abstinence syndrome.

The diagnostic power of cEV miR-137 was consistent regardless of the duration of abstinence or use, and it was particularly effective in younger individuals, suggesting that age influences its diagnostic capability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating microRNA miR-137 as a stable biomarker for methamphetamine abstinence. Kim, B., Tag, SH., Kim, YS., et al.[2022]

In a study of 57 heroin-dependent patients, two specific circulating miRNAs, miR-320a and let-7b-5p, were found to be significantly upregulated compared to healthy controls, suggesting their potential as biomarkers for diagnosing heroin use disorder.

The combination of these miRNAs showed a promising diagnostic accuracy with an area under the curve (AUC) of 0.782, indicating a sensitivity of 73.7% and specificity of 82.6%, which could help in identifying individuals with heroin dependence non-invasively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased Expression of Plasma miRNA-320a and let-7b-5p in Heroin-Dependent Patients and Its Clinical Significance. Liu, H., Xu, W., Feng, J., et al.[2021]

After 30 days of forced abstinence from morphine, rats showed an increased motivation to seek the drug, indicating that cravings can intensify over time even after cessation.

Specific microRNAs (miRNAs), particularly mir-32-5p and mir-1298-5p, were identified as potential biomarkers for drug-seeking behavior, with their expression levels correlating with drug intake and relapse, suggesting they could help track long-term effects of opioid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

microRNA expression levels in the nucleus accumbens correlate with morphine-taking but not morphine-seeking behaviour in male rats. Gillespie, A., Mayberry, HL., Wimmer, ME., et al.[2023]

Neonatal abstinence syndrome (NAS) is a complex condition resulting from opioid exposure in utero, and understanding genetic and epigenetic markers is essential for predicting its severity and outcomes.

Recent studies suggest that genetic changes and neuroinflammation linked to prenatal opioid exposure could lead to new therapeutic strategies and better management of NAS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the genomics of neonatal abstinence syndrome. Yen, E., Gaddis, N., Jantzie, L., et al.[2023]

In a study of 68 pregnant women, researchers found that specific microRNAs (miRNAs) in maternal blood can help predict infant outcomes related to fetal alcohol spectrum disorders (FASD), particularly distinguishing between affected and unaffected infants.

The study identified 11 elevated miRNAs in mothers of infants with significant alcohol exposure and used a classification model that combined these miRNAs with factors like smoking history and socioeconomic status, achieving a 13% misclassification rate in predicting infant outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma miRNA Profiles in Pregnant Women Predict Infant Outcomes following Prenatal Alcohol Exposure. Balaraman, S., Schafer, JJ., Tseng, AM., et al.[2018]

MicroRNAs (miRNAs) play a crucial role in regulating gene expression related to substance addiction, influencing brain functions and neural adaptations due to repeated substance exposure.

This review highlights the potential of miRNAs as diagnostic tools and novel therapeutic targets for treating substance addiction, suggesting they could help in understanding and managing the disorder more effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

miRNAs and Substances Abuse: Clinical and Forensic Pathological Implications: A Systematic Review. Occhipinti, C., La Russa, R., Iacoponi, N., et al.[2023]

MicroRNA-124 and microRNA-181 were found to be upregulated in females with cocaine use disorder (CUD) compared to healthy controls, suggesting their potential as biomarkers for this addiction.

Higher levels of microRNA-181 were associated with increased cognitive and affective depressive symptoms in the CUD group, indicating a possible link between these miRNAs and mental health issues in addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral blood microRNA levels in females with cocaine use disorder. Viola, TW., Heberle, BA., Zaparte, A., et al.[2020]

Citations

1. withpower.com withpower.com/trial/phase-neonatal-abstinence-syndrome-2020-564f3

Genetic Testing for Neonatal Abstinence Syndrome Trial Overview The study is testing if certain microRNAs in the saliva (let-7a, miR-146a, miR-192) can predict treatment needs and outcomes for babies with ...

2. reporter.nih.gov reporter.nih.gov/search/DOSpEaX_vUCQOvdR2_97_g/project-details/10897772

Understanding the miRNA response to opioid withdrawal ... Project Narrative Infants with neonatal abstinence syndrome (NAS) experience prolonged hospital stays and poor neurodevelopmental outcomes, in-part because of ...

3. frontiersin.org frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1148618/full

Genome-wide profiling of miRNA-gene regulatory networks ... Our data shows upregulation of the let-7 family members in the maturation and growth phase of CMs (P09 to P23). While target gene ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8993911/

Prenatal opioid-exposed infant extracellular miRNA signature ... Infant cord blood extracellular miRNAs can proactively identify opioid-exposed neonates at high-risk for developing severe NOWS.

5. frontiersin.org frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1140400/full

A review of the genomics of neonatal abstinence syndrome This review will provide an overview of the role of genetics and epigenetics in short and longer-term NAS outcomes.

6. reporter.nih.gov reporter.nih.gov/search/IkPv9-6ytEievfPzHgCChg/project-details/10897772

Understanding the miRNA response to opioid withdrawal ... Understanding the miRNA response to opioid withdrawal and their uses as potential biomarkers for neonatal abstinence syndrome. Project Number5F30DA057094-03.

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05937594/microrna-biomarkers-for-neonatal-opioid-withdrawal-syndrome?country=Palau&city=Hershey

MicroRNA Biomarkers for Neonatal Opioid Withdrawal ... Infants with neonatal abstinence syndrome (NAS) experience prolonged hospital stays and poor neurodevelopmental outcomes, in-part because of ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0163725822001097

MicroRNAs in drug addiction: Current status and future ... Considerable studies have demonstrated that miRNAs are strong modulators of posttranscriptional gene expression in drug addiction.