Delivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder

NCT05053503 | Completed FDA Device

• 1 other identifier: SBM-OWP-03
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 4

Brief Summary

The primary objective of this trial is to determine whether tAN can improve relapse prevention beyond that seen with extended-release injectable naltrexone during Phase II.

Conditions

Opioid-use Disorder; Opioid Withdrawal

Keywords

auricular neurostimulation; vagus nerve stimulation; transcutaneous; withdrawal symptoms; relapse prevention

Outcome Measures

Primary Outcomes (2)

• 14-Panel Urine Drug Screen

  In Phase II, participants will provide a weekly urine sample to determine if opioids have been used in the past week (in conjunction with a self-report). A urine drug screen cup will be used to detect presence of: Amphetamines, Buprenorphine, Benzodiazepines, Cocaine, Ethyl Glucuronide, Fentanyl, Synthetic Marijuana, Ecstasy, Methamphetamines, Methadone, Opiates / Morphine, Oxycodone, Cannabinoid (Marijuana), and Tramadol. The urine drug screen cup also contains a temperature strip to confirm appropriate temperature of the sample and an adulteration panel for determination of sample tampering.

  Weekly throughout Phase II (13 weeks)

• Self-Report of Drug Use

  In Phase II, participants will be asked weekly to self-report any use of opioids to determine if opioids have been used in the past week (in conjunction with a UDS sample).

  Weekly throughout Phase II (13 weeks)

Secondary Outcomes (9)

• Clinical Opiate Withdrawal Scale (COWS)

  60 minutes after treatment initiation (Day 1, Phase I)

• Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop)

  60 minutes after treatment initiation (Day 1, Phase I)

• Clinical Opiate Withdrawal Scale (COWS)

  6 hours after treatment initiation (Day 1, Phase I)

• Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop)

  6 hours after treatment initiation (Day 1, Phase I)

• Clinical Opiate Withdrawal Scale (COWS)

  Daily on Days 2-7 of Phase I

Other Outcomes (12)

• Patient Health Questionnaire (PHQ-9) in Phase I

  Baseline and Day 7

• Patient Health Questionnaire (PHQ-9) in Phase II

  Monthly throughout Phase II (Day 28, 56, and 90)

• PTSD Checklist for DSM-5 (PCL-5) in Phase I

  Baseline and Day 7

Study Arms (6)

Active tAN + placebo

PLACEBO COMPARATOR

tAN will be delivered at a duty cycle of for 5 minutes ON and 10 seconds OFF for up to 168 hours (7 days) therapy duration. Stimulation intensity will be customized to the participants comfort level and within range of therapeutic effectiveness. Participants will receive 3 placebo pills four times per day for 7 days. The placebo will appear similar to lofexidine in size, shape, color, and smell to lofexidine.

Device: Sparrow Ascent Therapy System

Active tAN + lofexidine

ACTIVE COMPARATOR

tAN will be delivered at a duty cycle of for 5 minutes ON and 10 seconds OFF for up to 168 hours (7 days) therapy duration. Stimulation intensity will be customized to the participants comfort level and within range of therapeutic effectiveness. Participants will receive 3 lofexidine 0.18 mg/tablets four times per day (daily dose of 2.16 mg) for 7 days.

Device: Sparrow Ascent Therapy System; Drug: Lofexidine

Sham tAN + placebo

NO INTERVENTION

Participants will have the earpiece applied and the cable connected to the Patient Controller, but tAN stimulation will not be turned on. Participants will receive 3 placebo pills four times per day for 7 days. The placebo will appear similar to lofexidine in size, shape, color, and smell to lofexidine.

Sham tAN + lofexidine

SHAM COMPARATOR

Participants will have the earpiece applied and the cable connected to the Patient Controller, but tAN stimulation will not be turned on. Participants will receive 3 lofexidine 0.18 mg/tablets four times per day (daily dose of 2.16 mg) for 7 days.

Drug: Lofexidine

extended-release injectable naltrexone

ACTIVE COMPARATOR

Extended-release injectable naltrexone will be administered according to the clinical site's standard of care.

Drug: Extended-release injectable naltrexone

Active tAN + extended-release injectable naltrexone

EXPERIMENTAL

Extended-release injectable naltrexone will be administered according to the clinical site's standard of care. Participants will be provided with a Spark Sparrow Ascent Therapy System and instructed to administer therapy according to the specified frequencies: * Month 1 (Days 1 - 28): a minimum of 2 hours per day at least 5 days a week * Month 2 (Days 29 - 56): a minimum of 2 hours per day at least 3 days a week * Month 3 (Days 57 - 90: a minimum of 2 hours per day at least 1 day per week

Device: Sparrow Ascent Therapy System; Drug: Extended-release injectable naltrexone

Interventions

Sparrow Ascent Therapy System DEVICE

Transcutaneous auricular neurostimulation (tAN)

Active tAN + extended-release injectable naltrexone; Active tAN + lofexidine; Active tAN + placebo

Lofexidine DRUG

Participants will receive 3 lofexidine 0.18 mg/tablets four times per day (daily dose of 2.16 mg) for 7 days.

Active tAN + lofexidine; Sham tAN + lofexidine

Extended-release injectable naltrexone DRUG

Participants will receive extended-release injectable naltrexone based on the clinical site's standard of care.

Active tAN + extended-release injectable naltrexone; extended-release injectable naltrexone

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant shows signs of current opioid dependence; prescription or non-prescription
• Participant COWS score is ≥ 8 or in the opinion of the investigator the participant is in mild to moderate withdrawal at the baseline assessment
• Participant is between 18 and 65 years of age
• Participant is English proficient
• Participant is able to provide informed consent and function at an intellectual level sufficient for study requirements

You may not qualify if:

• Participant presents current evidence of an uncontrolled and/or clinically significant medical condition or psychiatric condition
• Participant has a history of epileptic seizures
• Participant has a history of neurological diseases or traumatic brain injury
• Participants using long-acting opioids such as methadone or buprenorphine for a period of five or more consecutive days prior to enrollment
• Participant has recent suicide attempt leading to current hospital admission or continued expressed suicidal ideation
• Participant has presence of devices, e.g., pacemakers, cochlear prosthesis, neurostimulators
• Participant has abnormal ear anatomy or ear infection present
• Participant is unwilling to transition to opioid antagonist medication following acute detox treatment
• Women of childbearing potential, not using adequate contraception as per investigator judgment or not willing to comply with contraception for the duration of the study
• Females who are pregnant or lactating
• Participant has any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial

Sponsors & Collaborators

• Spark Biomedical, Inc.: lead
• Hazelden Betty Ford Foundation: collaborator
• Gaudenzia, Inc.: collaborator

Study Sites (4)

Hazelden Betty Ford Foundation

Rancho Mirage, California, 92270, United States

Location

Gaudenzia, Inc.

Crownsville, Maryland, 21032, United States

Location

Hazelden Betty Ford Foundation

Center City, Minnesota, 55012, United States

Location

Hazelden Betty Ford Foundation

Plymouth, Minnesota, 55441, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders; Substance Withdrawal Syndrome

Interventions

lofexidine

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All study investigators will be blind to patient treatment group assignment. Furthermore, each clinical site will use qualified COWS assessors that will be blind to randomization group assignment. This will ensure a non-biased assessment of opioid withdrawal symptoms. Information regarding study intervention will be withheld from the blinded COWS assessors. All participants will be blinded to their group assignment during acute detox treatment (Phase I). Participants will not be unblinded to their Phase I treatment until study exit, which may occur at the end of Phase II for participants who continue in the study. Participants will not be blinded to their treatment group during Phase II.
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a prospective, randomized, controlled, multi-center, clinical trial in which participants with a history of dependence on prescriptive or non-prescriptive opioids will be randomized 2:1 into one of four treatment groups during Phase I (acute detoxification). Phase I will occur during the participant's treatment in a residential detox center. Participants will have the option to continue into Phase II of the trial at the conclusion of their stay in the residential detox treatment program. In Phase II, participants will be re-randomized 1:1 into one of two treatment groups.

Study Record Dates

• First Submitted: August 16, 2021
• First Posted: September 22, 2021
• Study Start: May 27, 2022
• Primary Completion: April 4, 2025
• Study Completion: April 4, 2025
• Last Updated: July 4, 2025

Record last verified: 2025-07

Locations

US (4)