Contemporary Clinical Trials Communications 21 (2021) 100737 Available online 11 February 2021 2451-8654/© 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 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 Elisabeth Bloch-Salisbury a, b, 1, * , Debra Bogen b , Mark Vining a , Dane Netherton c , Nicolas Rodriguez a , Tory Bruch b , Cheryl Burns d , Emily Erceg d , Barbara Glidden a , Didem Ayturk c , Sanjay Aurora a , Toby Yanowitz b , Bruce Barton c , Sue Beers e a Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, 01655, USA b Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA c Department of Population and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, 01655, USA d University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA e Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA A R T I C L E INFO Keywords: Infant drug withdrawal Neonatal abstinence syndrome Neonatal opioid withdrawal syndrome Maternal substance use during pregnancy Developmental outcomes Stochastic resonance ABSTRACT The incidence of Neonatal Abstinence Syndrome (NAS) continues to rise and there remains a critical need to develop non-pharmacological interventions for managing opioid withdrawal in newborns. Objective physiologic markers of opioid withdrawal in the newborn remain elusive. Optimal treatment strategies for improving short- term clinical outcomes and promoting healthy neurobehavioral development have yet to be defned. This dual- site randomized controlled trial (NCT02801331) is designed to evaluate the therapeutic effcacy of stochastic vibrotactile stimulation (SVS) for reducing withdrawal symptoms, pharmacological treatment, and length of hospitalization, and for improving developmental outcomes in opioid-exposed neonates. Hospitalized newborns (n = 230) receiving standard clinical care for prenatal opioid exposure will be randomly assigned within 48- hours of birth to a crib with either: 1) Intervention (SVS) mattress: specially-constructed SVS crib mattress that delivers gentle vibrations (30–60 Hz, ~12 μm RMS surface displacement) at 3-hr intervals; or 2) Control mattress (treatment as usual; TAU): non-oscillating hospital-crib mattress. Infants will be studied throughout their hospitalization and post discharge to 14-months of age. The study will compare clinical measures (i.e., withdrawal scores, cumulative dose and duration of medications, velocity of weight gain) and characteristic progression of physiologic activity (i.e., limb movement, cardio-respiratory, temperature, blood-oxygenation) throughout hospitalization between opioid-exposed infants who receive SVS and those who receive TAU. Developmental outcomes (i.e., physical, social, emotional and cognitive) within the frst year of life will be evaluated between the two study groups. Findings from this randomized controlled trial will determine whether SVS reduces in-hospital severity of NAS, improves physiologic function, and promotes healthy development. 1. Introduction Opioid-use during pregnancy and post-natal effects on the neonate continues to be a growing and costly public health problem [1–5]. Particularly alarming is the high rate of use and misuse of prescription opioids, with reports of use of these extremely addictive narcotic pain Abbreviations: EMR, Electronic Medical Record; NAS, Neonatal Abstinence Syndrome; UMass, UMass Memorial Healthcare (Coordinating/Primary study site); UPitt, University of Pittsburgh (Consortium study site); NICU, Neonatal Intensive Care Unit; NN, Newborn Nursery; SVS, Stochastic vibrotactile stimulation (intervention-mattress condition); TAU, Treatment as usual (control condition). * Corresponding author. Department of Psychiatry University of Pittsburgh School of Medicine, 3501 Forbes Avenue, Pittsburgh, PA, 15213, USA. E-mail address: salisburye2@upmc.edu (E. Bloch-Salisbury). 1 Current address: Department of Psychiatry, University of Pittsburgh School of Medicine, 3501 Forbes Avenue, Pittsburgh, PA, 15213. Contents lists available at ScienceDirect Contemporary Clinical Trials Communications journal homepage: http://www.elsevier.com/locate/conctc https://doi.org/10.1016/j.conctc.2021.100737 Received 2 October 2020; Received in revised form 12 January 2021; Accepted 29 January 2021