NCT05834478

Brief Summary

This study is being done to answer the question: what is the effect of Vagal Nerve Stimulation (VNS) dosing on opioid withdrawal responses in individuals with a history of Opioid Use Disorders (OUDs)? Eligible participants will be in the study for one week in an inpatient research hospital stay, have an MRI scan, and have a follow-up call 1-3 months after their inpatient stay. Participants will complete several psychiatric questionnaires/interviews, physiological monitoring with several devices, brain imaging, and VNS testing.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
103

participants targeted

Target at P25-P50 for phase_3

Timeline
11mo left

Started Feb 2024

Typical duration for phase_3

Geographic Reach
1 country

6 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress71%
Feb 2024Apr 2027

First Submitted

Initial submission to the registry

March 14, 2023

Completed
2 months until next milestone

First Posted

Study publicly available on registry

April 28, 2023

Completed
10 months until next milestone

Study Start

First participant enrolled

February 20, 2024

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2027

Expected
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2027

Last Updated

March 27, 2026

Status Verified

March 1, 2026

Enrollment Period

3 years

First QC Date

March 14, 2023

Last Update Submit

March 24, 2026

Conditions

Keywords

Non-invasive Vagal Nerve StimulationVagus nervevagus nerve stimulationOUD

Outcome Measures

Primary Outcomes (2)

  • Change in Peak Subjective Opiate Withdrawal Scale (SOWS) Score

    All participants will complete the Subjective Opiate Withdrawal Scale (SOWS). The total score on each day will be compared between active tcVNS versus sham stimulation. The SOWS is performed four times daily. The total SOWS score is the sum of the individual item scores and ranges from 0 to 64, with a higher score indicating greater withdrawal severity.

    Day 2, Day 3

  • Safety of tcVNS use

    Defined as the absence of device related adverse events.

    Up to 7 days after study initiation

Secondary Outcomes (12)

  • Study retention

    Baseline, Up to 10 days after study initiation

  • Treatment adherence

    3 months

  • Change in brain dopamine D1 and D2/3 receptor regional binding potentials

    Day 2, Day 3

  • Change in heart rate

    Baseline, Day 2, Day 3

  • Change in inflammatory biomarkers

    15 minutes before stress and up to 180 minutes post-stress

  • +7 more secondary outcomes

Study Arms (2)

Transcutaneous Cervical Vagal Nerve Stimulation Device

EXPERIMENTAL

Stimulation with the tcVNS

Device: Transcutaneous Cervical Vagal Nerve StimulationDrug: [F-18]Fallypride

Sham Stimulation Device

SHAM COMPARATOR

Stimulation with the sham device.

Device: Sham StimulationDrug: [F-18]Fallypride

Interventions

\[F-18\]Fallypride is a radioactive material. Each patient will have two \[F-18\]Fallypride PET scans. For each scan \[F-18\]Fallypride will be injected as an intravenous bolus. The radiation dose to body organs in this study is well within the Food and Drug Administration (FDA) national guidelines for radiation exposure for human research studies and less than the total amount that is permitted for research studies in one year.

Also known as: Radiolabeled material
Sham Stimulation DeviceTranscutaneous Cervical Vagal Nerve Stimulation Device

Participants will receive stimulation of the vagus nerve with the non-invasive transcutaneous cervical Vagal Nerve Stimulation (tcVNS), which does not require surgery or implantation, and electrically stimulates the vagus nerve as it passes through the neck, dampening the sympathetic nervous system and modulating brain regions to a single side of the neck with the GammaCore device. Participants will be trained on self-stimulation and from days 1-7 patients undergo four times daily self-stimulation with tcVNS first for two minutes on one side, followed by a one-minute pause, then two minutes on the same side. The intensity of the stimulus (i.e. the current amplitude) will be adjusted by the user, to the maximum tolerable level without causing excessive pain \[typically 10-30 V and 60milliamperes (mA) (peak)\], with an alternating current (AC) signal consisting of five 5 kilohertz (kHz) pulses 200 microseconds in duration, repeating at a rate of 25 Hz (about once every 40 milliseconds).

Also known as: tcVNS
Transcutaneous Cervical Vagal Nerve Stimulation Device

Participants will have the same procedures as with the tcVNS but will instead receive a device that appears identical to the active tcVNS device in look, weight, visual and audible feedback, and also in user controls. The Sham device looks and sounds like an active device but does not deliver an electric current.

Also known as: Sham stimulation of vagus nerve
Sham Stimulation Device

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Meet criteria for OUDs based on the DSM5 criteria
  • Willing to undergo supervised withdrawal
  • Willing to be transitioned to a MOUD or behavioral management during treatment aftercare

You may not qualify if:

  • Positive pregnancy test or breastfeeding for women
  • History of meningitis
  • Traumatic brain injury
  • Current treatment with methadone, naltrexone, or Suboxone or medications that would be contraindicated with hydromorphone or clonidine administration
  • History of head trauma resulting in loss of consciousness (LOC) of greater than one minute where the LOC is not judged to be primarily related to overdose in the judgment of the study physician
  • Past year moderate to severe non-opioid use disorders that would require separate withdrawal management
  • Current or lifetime history of schizophrenia, schizoaffective disorder, or bulimia
  • History of serious medical or neurological illness or organic mental disorder, including liver disease, but also including cardiovascular, gastrointestinal, hepatic, renal, neurologic, or other systemic illness, including liver enzymes aspartate transaminase (AST) and alanine transaminase (ALT) more than three times upper limit of normal, that would preclude involvement based on the clinical judgment of the study psychiatrist
  • Lack of venous access that would preclude PET imaging
  • History of shrapnel or other foreign bodies that would preclude MRI scanning
  • Positive test for COVID-19

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Emory University Clinical Research Network

Atlanta, Georgia, 30322, United States

RECRUITING

Health Sciences Research Building

Atlanta, Georgia, 30322, United States

NOT YET RECRUITING

Rollins School of Public Health

Atlanta, Georgia, 30322, United States

RECRUITING

12 Executive Park Drive

Atlanta, Georgia, 30329, United States

RECRUITING

Emory University

Atlanta, Georgia, 30329, United States

RECRUITING

Georgia Institute of Technology

Atlanta, Georgia, 30332, United States

RECRUITING

MeSH Terms

Conditions

Substance Withdrawal SyndromeOpioid-Related Disorders

Condition Hierarchy (Ancestors)

Substance-Related DisordersChemically-Induced DisordersMental DisordersNarcotic-Related Disorders

Study Officials

  • James D Bremner, MD

    Emory University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

James D Bremner, MD

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

March 14, 2023

First Posted

April 28, 2023

Study Start

February 20, 2024

Primary Completion (Estimated)

February 1, 2027

Study Completion (Estimated)

April 1, 2027

Last Updated

March 27, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will share

At the conclusion of the trial, the data will be stripped of identifiers prior to release for sharing and will be made available in de-identified form to other investigators and other sites.

Access Criteria
Investigators will make the data and associated documentation available to users only under a data-sharing agreement that provides for (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.

Locations