Efficacy and Outcomes of a Non-Pharmacological Intervention for Neonatal Abstinence Syndrome

A Randomized Controlled Study of Stochastic Vibrotactile Stimulation for Neonatal Abstinence Syndrome: Therapeutic Efficacy and Neurobehavioral Outcomes

The purpose of this study is to examine the efficacy of a specially-constructed crib mattress that delivers gentle vibrations (stochastic vibrotactile stimulation) as a complementary, non-pharmacological intervention for treating drug withdrawal in newborns exposed to opioids in utero.

Study Overview

• Status: Completed
• Conditions: Neonatal Abstinence Syndrome
• Intervention / Treatment: Device: Stochastic Vibrotactile Stimulation (SVS)

Detailed Description

This study will test the therapeutic efficacy of stochastic vibrotactile stimulation (SVS) for reducing withdrawal symptoms, pharmacological treatment and hospitalization, and for improving neurobehavioral developmental outcomes in opioid-exposed newborns.

Candidates at-risk for NAS due opioid exposure in utero will be identified to investigators by medical caregiver and/or prescreened using HIPAA Waiver for recruitment (maternal-prenatal; infant-postnatal). Infants will be randomized into either SVS (complementary to standard of care) or Treatment as Usual (TAU), restricted by equipment (mattress) availability. Infants will be enrolled and assigned to a condition within 48 hours post birth and participate throughout hospitalization. Infants assigned SVS will receive daily intervention of continuous intervals of SVS throughout hospitalization using a specially constructed crib mattress that delivers gentle vibrations at preset intervals.

Specific Aim 1. Determine the efficacy of SVS as a non-pharmacological therapy complementary to standard of care for reducing severity and duration of opioid withdrawal in newborns compared to TAU alone. Quantify clinical variables: NAS severity, treatment days, days in hospital, velocity of weight gain, cumulative morphine dose.

Specific Aim 2. Compare neurobehavioral outcomes in fetal drug-exposed infants between infants who received SVS and those who received TAU. Longitudinal outcomes assessment at 6-months and 1 year to test whether early intervention with SVS compared to standard care improves physical, social, emotional and cognitive development.

• Study Type: Interventional
• Enrollment (Actual): 208
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 hour to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: Eligible subjects are infants currently in the NICU or Newborn Nursery at University of Massachusetts Memorial Hospital or at Magee Women's Hospital of UPMC and:

• Full-term infants (≥37 wks gestational age)
• Newborns at risk for NAS due to opioid-exposure in utero
• At-risk infants will be infants who present with confirmed meconium and/or urine toxicology report and/or documented medical record for opioids (e.g., methadone, buprenorphine/subutex, oxycodone, heroin); may also have prenatal exposure to benzodiazepines, barbiturates, amphetamines, cannabinoids, alcohol, nicotine and/or caffeine.

Exclusion Criteria: Eligible infants meeting the inclusion criteria above will be excluded from participation in the study if he/she:

• Born less than <37weeks.
• Has a clinically significant congenital abnormality
• Has a clinically significant fetal anomaly
• Has hydrocephalus or intraventricular hemorrhage >grade 2
• Has a seizure disorder not related to drug withdrawal
• Has a clinically significant cardiac shunt
• Has anemia (hemoglobin<8g/dL)
• Requires mechanical respiratory support
• Has MRSA or infection at time of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stochastic Vibrotactile Stimulation (SVS); Infants randomized to this arm will receive daily intervals of continuous SVS (ON) and no SVS (OFF) throughout hospitalization, starting within 48-hrs post birth. SVS will be complementary to standard of clinical care (e.g., clinically-determined pharmacological management; routine parental/volunteer holding; breast and/or bottle feed). Infants will be scored for severity of withdrawal using standardized, modified Finnegan scoring system by clinical care nurses per routine clinical care throughout hospitalization.	Device: Stochastic Vibrotactile Stimulation (SVS); Infant crib mattress will be replaced with a specially constructed mattress (non-commercially available) to provide gentle vibrations and sounds during mattress stimulations.
No Intervention: Treatment as Usual (TAU); Infants randomized to this arm will be enrolled within 48-hours post birth and receive treatment as usual (TAU)- standard of clinical care (e.g., clinically-determined pharmacological management, routine/volunteer holding; breast and/or bottle feed). Infants will not receive any SVS. Infants will be scored for severity of withdrawal using standardized, modified Finnegan scoring system by clinical care nurses per routine clinical care throughout hospitalization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacological Treatment-Dose	Cumulative morphine dose	Participants will be monitored for the duration of their hospitalization, which is an expected mean of 21 days
Pharmacological Treatment-Duration	Total days of morphine treatment	Participants will be monitored for the duration of their hospitalization, which is an expected mean of 21 days
Neurobehavioral Outcomes Assessment	Neurobehavioral infant assessment at 6 month followup	Participants will be assessed at approx 1 month, 6 months, and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Velocity of weight gain	Trajectory of weight gain throughout hospitalization-Days to return to birth weight	Participants will be monitored for the duration of their hospitalization, which is an expected mean of 21 days
Hospitalization length of stay	Duration of infant hospitalization	Participants will be monitored for the duration of their hospitalization, which is an expected mean of 21 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory rate	Respiratory rate at 1 and/or 2 weeks of age assessed for about 12 consecutive hours in a subset of hospitalized subjects	Assess respiratory rate for about 12 consecutive hours at week 1 and week 2 of infant hospitalization
Cardiac activity	Heart rate at 1 and/or 2 weeks of age assessed for about 12 consecutive hours in a subset of hospitalized subjects	Assess heart rate for about 12 consecutive hours at week 1 and week 2 of infant hospitalization

Collaborators and Investigators

• Sponsor: Elisabeth Salisbury, PhD
• Collaborators: National Institute on Drug Abuse (NIDA); University of Pittsburgh
• Investigators: Principal Investigator: Elisabeth B Salisbury, Ph.D., University of Massachusetts, Worcester

Publications and helpful links

General Publications

• Pahl A, Young L, Buus-Frank ME, Marcellus L, Soll R. Non-pharmacological care for opioid withdrawal in newborns. Cochrane Database Syst Rev. 2020 Dec 21;12(12):CD013217. doi: 10.1002/14651858.CD013217.pub2.
• Bloch-Salisbury E, Bogen D, Vining M, Netherton D, Rodriguez N, Bruch T, Burns C, Erceg E, Glidden B, Ayturk D, Aurora S, Yanowitz T, Barton B, Beers S. Study design and rationale for a randomized controlled trial to assess effectiveness of stochastic vibrotactile mattress stimulation versus standard non-oscillating crib mattress for treating hospitalized opioid-exposed newborns. Contemp Clin Trials Commun. 2021 Feb 11;21:100737. doi: 10.1016/j.conctc.2021.100737. eCollection 2021 Mar.

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2017
• Primary Completion (Actual): March 5, 2021
• Study Completion (Actual): June 6, 2021

Study Registration Dates

• First Submitted: June 9, 2016
• First Submitted That Met QC Criteria: June 9, 2016
• First Posted (Estimate): June 15, 2016

Study Record Updates

• Last Update Posted (Actual): February 23, 2022
• Last Update Submitted That Met QC Criteria: February 21, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Substance Abuse; Stochastic Resonance; Fetus/Newborn Infant; Drug Withdrawal
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Substance-Related Disorders; Disease; Infant, Newborn, Diseases; Syndrome; Neonatal Abstinence Syndrome
• Other Study ID Numbers: STUDY21040054; 1R01DA042074-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No