Neurostimulation for Opiate Withdrawal in the PICU (NOW)

Efficacy of Neurostimulation on Opiate Withdrawal Symptoms in Pediatric ICU Patients

This is a prospective pilot study to investigate the effects of Percutaneous Electrical Nerve Field Stimulation (PENFS) on symptoms of opioid withdrawal in pediatric patients in the intensive care unit.

Study Overview

• Status: Withdrawn
• Conditions: Opiate Withdrawal Syndrome
• Intervention / Treatment: Device: Percutaneous Electrical Nerve Field Stimulation

Detailed Description

This is a prospective, unblinded, randomized controlled pilot trial to evaluate the impact of the BRIDGE device when used on patients at high risk of opioid withdrawal following opioid exposure.

The investigator team hypothesized that treatment of pediatric intensive care unit (PICU) patients (ages 5-17 years) with PENFS will prevent the development of opioid withdrawal symptoms, reduce the need for long-acting opioid agonists or pharmacological rescue agents to treat withdrawal, and decrease overall PICU length of stay (LOS).

Aim 1: Withdrawal, using the Withdrawal Assessment Tool (WAT-I) is less for those using PENFS device than for those receiving standard of care (SOC) treatment.

H1: The WAT-I will be lower in the PENFS group than the SOC group and this will be true, even after adjusting for age and total opioid dose/kg pre-weaning.

Aim 2: For withdrawal symptoms of nausea, vomiting or pain, those receiving PENFS compared to SOC will require less treatment for these symptoms.

H2: The PENFS groups compared to the SOC will have primarily fewer episodes of gastrointestinal distress and lower pain scores resulting in the use of fewer doses of rescue medications; further this will be true after adjusting for total opioid dose/kg pre- weaning.

Aim 3: PICU LOS will be less for those receiving the PENFS device compared to those receiving SOC treatment.

H3: Following the initiation of weaning, the PICU LOS will be less for those with PENFS than those with SOC. This will be true after adjusting for age and total opioid dose/kg pre-weaning.

The following inclusion and exclusion criteria will be used to determine eligibility for this study:

Inclusion:

• Children aged 5 to 17 years
• Admission to PICU at Children's Hospital of Wisconsin (CHW)
• Exposure to at least 120 hours of continuous IV opioid administration.

Exclusion:

• Age children <5 years
• Known central nervous system injury (hypoxic ischemic injury, traumatic brain injury, postoperative craniotomies),
• Plan to wean benzodiazepine dosing during the active study period
• Patients who are developmentally delayed
• Defined as inappropriately non-verbal for age and determined through review of the medical record and discussion with the PICU attending and consulting team members.
• Known pregnancy
• Any pregnancy testing done during the subject's hospitalization will be reviewed.

(This will only be monitored if required as SOC, but will not be collected for the purpose of the study alone.)

• Known seizure disorder
• Known diagnosis of psoriasis or significant dermatological disease involving ear (?)
• Patients with implantable devices (cardiac pacemaker, vagal nerve stimulator, etc.)

After consent, and prior to the initiation of opiate withdrawal initiation, subjects will be randomized to receive the local standard methadone wean or placement of the BRIDGE device. Randomization will be used to balance age (5-9 yrs., >9 yrs.) and gender (male, female) assigning subjects in a 1:1 ratio to the Bridge device or control groups.

Subjects in the treatment group will have the device placed immediately following their last scheduled opiate dose. The device will be active continuously for 120 hours from the time of placement. As needed (PRN) dosing of pain medication will be available for breakthrough symptoms experienced by the subject. Subjects randomized to the SOC group will begin SOC treatment per the PICU withdrawal protocol.

The BRIDGE device will be placed per manufacturer protocol. Electrodes will be placed percutaneously in the external ear with the help of a transilluminator to visualize the neurovascular bundles; three electrodes will be placed on the ventral and one on the dorsal aspect of the ear. The electrodes will be taped and secured behind the ear next to the generator itself which is secured to the skin with adhesive.

The electrode/needle arrays are placed according to the individual's distribution of neurovascular bundles. The exact location of the placement will vary slightly from person to person and is determined by both knowledge of auricular neuro-anatomy and visualization of the neurovascular bundles by transillumination (IHS, Versailles, IN, USA). The points will be targeted by four-point electrical stimulation using the BRIDGE device after carefully disinfecting the ear. The contents of the Neurostimulation will be delivered below sensation threshold for 5 consecutive days (120 hours).

Removal of the device will be done by a member of the study team if the patient is still admitted to CHW, or by the subject's parents if discharge takes place prior to the completion of the PENFS treatment. The device will be placed in a sharps discard container after removal. Subjects who will be discharged with the device will be provided with a sharps disposal bag that can be used to hold the device after removal. This bag can be discarded in any sharps container accessible to the subject or brought back to CHW and discarded the time of their next follow up appointment. If the subject's family is not comfortable removing the device at home the study team will make arrangements for the family to return to CHW for device removal.

If a patient in the PENFS group is experiencing significant breakthrough withdrawal symptoms (consistent WAT-I score of >4) for more than 48 hours, the PI and care team will meet to discuss whether scores are due to withdrawal symptoms or are being artificially inflated due to confounding factors. If the patient is determined to be experiencing significant symptoms of withdrawal, the device will be removed early, and the subject will be transitioned to SOC withdrawal treatment. At that point the patient will be considered to have withdrawn from study.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children aged 5 to 17 years
• Admission to PICU at Children's Hospital of Wisconsin (CHW)
• Exposure to at least 120 hours of continuous IV opioid administration.

Exclusion Criteria:

• Age children <5 years
• Known central nervous system injury (hypoxic ischemic injury, traumatic brain injury, postoperative craniotomies),
• Plan to wean benzodiazepine dosing during the active study period

• Patients who are developmentally delayed

  o Defined as inappropriately non-verbal for age and determined through review of the medical record and discussion with the PICU attending and consulting team members.

• Known pregnancy

  o Any pregnancy testing done during the subject's hospitalization will be reviewed. This will only be monitored if required as SOC, but will not be collected for the purpose of the study alone.

• Known seizure disorder
• Known diagnosis of psoriasis or significant dermatological disease involving ear (?)
• Patients with implantable devices (cardiac pacemaker, vagal nerve stimulator, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intervention Group; 50% of subjects will be randomized to the Intervention group and will receive percutaneous electric nerve field stimulation (PENFS) through the BRIDGE Device for 120 hours to treat withdrawal symptoms in patients following opiate exposure in the PICU.	Device: Percutaneous Electrical Nerve Field Stimulation; Placement of the PENFS device immediately following the last scheduled opiate dose in the PICU with active stimulation for 120 hours.; Other Names: BRIDGE Device
NO_INTERVENTION: Standard of Care Group; 50% of subjects will be randomized to the Standard of Care group and will receive be started on the standardized PICU Methadone wean for patients following opiate exposure in the PICU.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Withdrawal Assessment Tool (WAT-1) Score	Measurement of opiate withdrawal symptoms experienced by study subjects	Study Day 0 through Study Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Medication Use	Total dose of pain medications used on each study day	Study Day 0 through Study Day 5
Pain Scores	Age appropriate pain score values for each study day	Study Day 0 through Study Day 5
Length of Stay	Time PICU Admission to medical PICU discharge	PICU Admission

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2019
• Primary Completion (ACTUAL): October 22, 2020
• Study Completion (ACTUAL): October 22, 2020

Study Registration Dates

• First Submitted: June 3, 2019
• First Submitted That Met QC Criteria: June 3, 2019
• First Posted (ACTUAL): June 5, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 26, 2020
• Last Update Submitted That Met QC Criteria: October 22, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Pediatrics; Neurostimulation; Pediatric Intensive Care Unit; Opiate Withdrawal; Percutaneous Electric Nerve Field Stimulation
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Substance Withdrawal Syndrome
• Other Study ID Numbers: 1185104

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