Non-invasive Vagal Nerve Stimulation in Opioid Use Disorders UH3

Non-invasive Vagal Nerve Stimulation in Opioid Use Disorders UH3 (NCT05834478) is a Phase 3 interventional studying Withdrawal Symptoms and Opioid Use Disorder, sponsored by Emory University. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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.

What Stage of Research Is This?

Phase 3 trials confirm efficacy and safety in large patient groups (often 300–3,000+) and form the evidence base for an FDA approval submission. For Withdrawal Symptoms, Phase 3 studies typically randomize participants between the investigational treatment and either a placebo or current standard of care. A successful Phase 3 result is the threshold most treatments need to clear before regulatory approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 103 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Withdrawal Symptoms subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 Who Should NOT Join This Trial: - 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 - Active implantable device (i.e. pacemaker) or other VNS device exclusion - History of shrapnel or other foreign bodies that would preclude MRI scanning - Positive test for COVID-19 Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * 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 Exclusion Criteria: * 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 * Active implantable device (i.e. pacemaker) or other VNS device exclusion * History of shrapnel or other foreign bodies that would preclude MRI scanning * Positive test for COVID-19

Treatments Being Tested

DEVICE

Transcutaneous Cervical Vagal Nerve Stimulation

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).

DEVICE

Sham Stimulation

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.

DRUG

[F-18]Fallypride

\[F-18\]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.

Locations (6)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Emory University Clinical Research Network