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

Trial Summary

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment for Neonatal Abstinence Syndrome?

The research suggests that certain microRNAs, like let-7b, can serve as biomarkers for diagnosing substance use disorders, indicating their potential role in understanding and possibly treating conditions related to substance exposure, such as Neonatal Abstinence Syndrome. ^{1 2 3 4 5}

How does genetic testing differ from other treatments for neonatal abstinence syndrome?

Genetic testing for neonatal abstinence syndrome (NAS) is unique because it focuses on identifying genetic and epigenetic markers that can predict the severity and outcomes of NAS, rather than directly treating the symptoms. This approach aims to improve diagnosis and management by understanding individual genetic predispositions, which is different from traditional treatments that primarily address withdrawal symptoms after birth. ^{1 3 4 6 7}

What is the purpose of this trial?

Infants with neonatal abstinence syndrome (NAS) experience prolonged hospital stays and poor neurodevelopmental outcomes, in-part because of the lack of accurate, individualized, biologic assessments available to manage this increasingly common medical condition. The proposed study will define the molecular mechanisms that regulate the response to opioid withdrawal in the developing brain by focusing on three candidate microRNAs (let-7a, miR-146a, miR-192) that have been shown to respond to opioid exposure in animal models and adults, and are impacted in both my preliminary study of infants with NAS, and my human neural progenitor cell (NPC) design of opioid withdrawal. By determining the mechanism through which microRNAs impact NPC differentiation in opioid withdrawal, and determining whether exosomal salivary microRNA levels predict treatment dose and neurodevelopmental outcomes in infants with NAS, this study will enhance our knowledge of NAS-related biology and identify potential biomarkers that could improve medical care for this important medical condition.

Research Team

Steven D. Hicks, MD, PhD

Principal Investigator

Associate Professor of Pediatrics

Eligibility Criteria

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

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

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)

Exclusion Criteria

Infant exposure to magnesium sulfate

<35 week gestation

My newborn is receiving sugar water for low blood sugar and was exposed to opioids.

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Increased Expression of Plasma miRNA-320a and let-7b-5p in Heroin-Dependent Patients and Its Clinical Significance. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Circulating microRNA miR-137 as a stable biomarker for methamphetamine abstinence. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Peripheral blood microRNA levels in females with cocaine use disorder. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

miRNAs and Substances Abuse: Clinical and Forensic Pathological Implications: A Systematic Review. [2023]

5. France pubmed.ncbi.nlm.nih.gov

microRNA expression levels in the nucleus accumbens correlate with morphine-taking but not morphine-seeking behaviour in male rats. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Plasma miRNA Profiles in Pregnant Women Predict Infant Outcomes following Prenatal Alcohol Exposure. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A review of the genomics of neonatal abstinence syndrome. [2023]