Neurostimulation for Neonatal Opioid Withdrawal Syndrome

(SPROUT Trial)

Not currently recruiting at 2 trial locations

Overseen By Caroline Benner

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Spark Biomedical, Inc.

Must be taking: Morphine

Must not be taking: Methadone

Disqualifiers: Unstable infants, Cardiomyopathy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the Roo tAN Therapy System, a type of neurostimulation, can reduce the duration infants require oral morphine for Neonatal Opioid Withdrawal Syndrome (NOWS). The trial will compare two groups: one receiving active tAN therapy with morphine and another receiving sham (inactive) tAN therapy with morphine. Infants over 33 weeks gestational age who need morphine for withdrawal and are stable without extra breathing support are suitable candidates for this trial. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could enhance treatment for NOWS.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if participants must stop taking their current medications. However, since the trial involves infants with Neonatal Opioid Withdrawal Syndrome, it is likely that they will continue their current morphine treatment as part of the study.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It focuses on infants with Neonatal Opioid Withdrawal Syndrome who are already receiving morphine therapy.

What prior data suggests that the Roo tAN Therapy System is safe for neonatal opioid withdrawal syndrome?

Research has shown that the Roo tAN Therapy System is generally safe for babies with Neonatal Opioid Withdrawal Syndrome (NOWS). Early results suggest that this neurostimulation, which sends electrical signals to specific nerves, is well-tolerated. Importantly, studies indicate that the therapy might offer a promising alternative to reduce the duration infants require medications like morphine. Notably, there have been no significant reports of serious side effects with this treatment, which is encouraging for its use in newborns. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Roo tAN Therapy System because it offers a novel approach to managing Neonatal Opioid Withdrawal Syndrome (NOWS), a condition traditionally treated with morphine. Unlike the standard method that primarily relies on medication to ease withdrawal symptoms, the Roo tAN Therapy System uses transcutaneous auricular neurostimulation (tAN), a non-invasive technique that stimulates nerve pathways through the skin, potentially reducing dependency on opioids like morphine. This method not only targets the neurological aspects of withdrawal but also may help shorten hospital stays and improve the comfort of newborns during the withdrawal process. By providing a drug-free alternative or supplement to traditional treatments, this therapy could revolutionize the way NOWS is managed.

What evidence suggests that the Roo tAN Therapy System is effective for Neonatal Opioid Withdrawal Syndrome?

Research has shown that the Roo tAN Therapy System, which participants in this trial may receive, can help reduce withdrawal symptoms in newborns exposed to opioids. In one study, babies who received tAN therapy had lower withdrawal symptoms, with scores averaging below 8 on the FNAST scale, which measures these symptoms. This therapy stimulates the ear to release the body's natural pain relievers, reducing the need for oral morphine. Additionally, the average time infants needed morphine decreased significantly from 23 days to about 13.3 days. These findings suggest that tAN therapy could be a promising treatment for managing withdrawal in newborns. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for newborns over 33 weeks gestational age with Neonatal Opioid Withdrawal Syndrome (NOWS) needing morphine therapy, who are either breathing on their own or have minimal respiratory support. It includes those stable after severe illness or brain injury but excludes very unstable infants, those with significant heart issues, abnormal ear anatomy, major congenital anomalies affecting breathing or circulation, wards of the state, and older than two weeks.

Inclusion Criteria

My newborn is opioid-dependent due to severe illness or injury but is stable.

My baby is over 33 weeks old, has withdrawal symptoms, and needs morphine.

I am breathing on my own or with minimal help.

Exclusion Criteria

My infant needs a lot of help with breathing.

Newborns who have withdrawal symptoms due to medication given to the mother during pregnancy will be excluded.

My newborn has been given methadone more than 6 times or for over 24 hours.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Inpatient Treatment

Neonates receive either active or sham tAN therapy along with morphine, with FNASS scoring every three hours

Up to 4 weeks

Continuous inpatient monitoring

Neurodevelopmental Follow-up

Participants' neurodevelopment is assessed at 3, 9, 18, and 24 months using ASQ-3 and SP-2; further assessment with BSID-III if needed

24 months

4 follow-up contacts

What Are the Treatments Tested in This Trial?

Interventions

• Roo tAN Therapy System
• Sham Roo tAN Therapy System
• Sham Sparrow Fledging Therapy System
• Sparrow Fledging Therapy System

Trial Overview The study tests if the Sparrow Fledging Therapy System (a type of neurostimulation therapy) can reduce how much oral morphine a baby needs after treatment starts compared to a sham system. The goal is to see if this therapy helps manage withdrawal symptoms more effectively in infants with NOWS.

How Is the Trial Designed?

Group I: Active tAN + Morphine Experimental Treatment 1 Intervention

Group II: Sham tAN + Morphine Placebo Group 1 Intervention

Roo tAN Therapy System is already approved in United States for the following indications:

Approved in United States as Roo System for:

• Neonatal Opioid Withdrawal Syndrome (NOWS)

Who Is Running the Clinical Trial?

Spark Biomedical, Inc.

Lead Sponsor

Trials

14

Recruited

560+

University of Texas Health Science Center San Antonio

Collaborator

Trials

1

Recruited

50+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

University of Texas Southwestern Medical Center

Collaborator

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

Transcutaneous auricular neurostimulation (tAN) significantly reduced opioid withdrawal symptoms, with a mean decrease of 7.0 points on the Clinical Opiate Withdrawal Scale (COWS) after 60 minutes of treatment, indicating a 45.9% reduction in symptoms.

The study demonstrated that tAN is a safe and effective non-opioid treatment for managing opioid withdrawal syndrome, achieving up to a 74.7% reduction in COWS scores over a 5-day period, supporting its FDA clearance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delivering transcutaneous auricular neurostimulation (tAN) to improve symptoms associated with opioid withdrawal: results from a prospective clinical trial. Tirado, CF., Washburn, SN., Covalin, A., et al.[2022]

In a pilot study involving 61 infants with Neonatal Opioid Withdrawal Syndrome (NOWS), there were no significant differences in hospital length of stay (LOS) or length of treatment (LOT) between those treated with morphine and those treated with methadone.

However, infants treated with methadone received significantly higher total opioid doses and had a higher rate of transfer to the Neonatal Intensive Care Unit (NICU) due to over sedation, indicating potential safety concerns with methadone compared to morphine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morphine versus methadone for neonatal opioid withdrawal syndrome: a randomized controlled pilot study. Sutter, MB., Watson, H., Yonke, N., et al.[2022]

The FDA has approved two non-invasive electrical nerve stimulators that can help alleviate acute opioid withdrawal symptoms by stimulating cranial nerves behind the ear, showing promise as an adjunct treatment.

This method of auricular electrical neural stimulation has the potential to enhance medication-assisted treatment for opioid detoxification, offering lower side effects and potentially improving patient adherence to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auricular neural stimulation as a new non-invasive treatment for opioid detoxification. Qureshi, IS., Datta-Chaudhuri, T., Tracey, KJ., et al.[2021]

Acupuncture has been found to be a safe and effective method for reducing withdrawal symptoms in infants suffering from neonatal abstinence syndrome (NAS), which is a growing concern due to rising cases.

This review suggests that acupuncture should be considered as a nonpharmacologic treatment option for managing NAS, alongside other supportive therapies, to help alleviate discomfort and developmental delays in affected infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Scoping Review of Acupuncture as a Potential Intervention for Neonatal Abstinence Syndrome. Jackson, HJ., Lopez, C., Miller, S., et al.[2020]

Transcutaneous auricular neurostimulation (tAN) is a safe and well-tolerated treatment for infants with neonatal opioid withdrawal syndrome (NOWS), showing no unexpected adverse effects during the trial.

In this study involving eight infants, tAN significantly reduced the average length of oral morphine treatment from the national average of 23 days to 13.3 days, suggesting it may be an effective non-opioid adjuvant therapy for NOWS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Neurostimulation (tAN): A Novel Adjuvant Treatment in Neonatal Opioid Withdrawal Syndrome. Jenkins, DD., Khodaparast, N., O'Leary, GH., et al.[2022]

Electrical auricular stimulation can reduce the severity of morphine withdrawal symptoms in rats, suggesting its potential as a non-invasive treatment option.

This method is based on principles of electroacupuncture and may serve as a helpful adjunct therapy for managing narcotic withdrawal syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trans-cranial electrical stimulation attenuates the severity of naloxone-precipitated morphine withdrawal in rats. Dougherty, PM., Dafny, N.[2019]

A feasibility study involving 12 participants demonstrated that auricular acupressure can be effectively integrated into the standard care for neonatal opioid withdrawal syndrome (NOWS), with 100% adherence to the treatment protocol by nurse practitioners.

Mothers reported high satisfaction with the acupressure treatment (mean scores of 3.8-4.0 out of 4.0), and a majority of healthcare providers expressed support for the method, indicating a positive reception for this non-pharmacologic approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of auricular acupressure as an adjunct treatment for neonatal opioid withdrawal syndrome (NOWS). Jackson, HJ., Lopez, C., Miller, S., et al.[2022]

In a review of 11 studies on neonatal opioid withdrawal syndrome (NOWS), methadone was found to be more effective than morphine for primary treatment outcomes, showing no significant difference in treatment duration or hospitalization time between the two.

Buprenorphine demonstrated the shortest treatment and hospitalization durations compared to both morphine and methadone, suggesting it may be a more efficient option for managing NOWS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of opioid replacement agents for neonatal opioid withdrawal syndrome: a systematic review and meta-analysis. Lee, JJ., Chen, J., Eisler, L., et al.[2022]

Early identification of infants at risk for opioid neonatal abstinence syndrome (NAS) is crucial for starting supportive care quickly, which can help manage withdrawal symptoms effectively.

Using standardized nonpharmacologic care and strict opioid weaning protocols can significantly reduce both the length of hospital stays and the duration of medication treatment for infants with NAS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid Neonatal Abstinence Syndrome: An Overview. Wexelblatt, SL., McAllister, JM., Nathan, AT., et al.[2019]

Infants with neonatal opioid withdrawal syndrome (NOWS) treated with a novel symptom-triggered methadone approach (STMA) had a significantly shorter median hospital length of stay (10.5 days) compared to those treated with a fixed-schedule methadone taper (FSMT) (17.0 days), indicating improved hospitalization outcomes.

The STMA also resulted in fewer methadone treatment days (2.5 days) compared to FSMT (11.7 days), suggesting that this approach not only reduces hospital time but also minimizes medication exposure for infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standard Fixed-Schedule Methadone Taper Versus Symptom-Triggered Methadone Approach for Treatment of Neonatal Opioid Withdrawal Syndrome. Wachman, EM., Minear, S., Hirashima, M., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7982745/

Transcutaneous Auricular Neurostimulation (tAN): A Novel ... During tAN therapy, all eight infants achieved average FNAST scores <8, indicating an overall reduction in withdrawal symptoms. All infants, except for one ( ...

2. sparkbiomedical.com sparkbiomedical.com/news-articles/roo-breakthrough

Spark's Roo Device receives FDA Breakthrough ... The Roo System's unique non-invasive therapy promotes the release of endogenous opioids (endorphins), supplanting the need for oral morphine.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12532841/

The protocol for a randomized, sham-controlled trial of ... An emerging intervention using transcutaneous auricular neurostimulation (tAN) is being developed to reduce opioid withdrawal symptoms, but its ...

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/19/NCT04588519/Prot_000.pdf

Version 8 09-22-20 Page 1 of 15 We hypothesize that tAN delivered for up to 60 minutes during peak withdrawal (1h before next morphine dose) will be safe, well tolerated and ...

5. withpower.com withpower.com/trial/phase-substance-withdrawal-syndrome-1-2022-61e13

Neurostimulation for Neonatal Opioid Withdrawal ... The results showed that the average time infants needed morphine was reduced from the national average of 23 days to just 13.3 days, with some infants needing ...

6. reporter.nih.gov reporter.nih.gov/project-details/10390149

RePORT RePORTER - National Institutes of Health (NIH) | Between 2000– 2012, national rates of NOWS increased 383% from 1.2 per 1000 births to 5.8 per 1000 births. These infants frequently require hospital stay in a ...