Non-invasive Vagal Nerve Stimulation in Opioid Use Disorders UH3

NCT ID: NCT05834478

Last Updated: 2025-03-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 103 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-20
• Study Completion Date: 2026-12-31

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.

Detailed Description

The purpose of this study is to look at Opioid Use Disorders (OUDs) and Vagal Nerve Stimulation (VNS). OUDs are conditions involving misuse or addiction to opiate-containing prescription pain medications or opioid-containing substances including heroin. OUDs are associated with symptoms of withdrawal upon discontinuation of the substance, which can include problems with concentration and sleep, irritability, rapid heart rate, and craving for opioids. Vagal Nerve Stimulation (VNS) is a procedure where the vagus nerve, which is in the neck, is electrically stimulated, much like a pacemaker is used to stimulate the heart. Branches of the vagus nerve travel throughout the brain and the body. Vagal nerve stimulation is felt to have positive effects on the brain and body by blocking the sympathetic (adrenaline) response that occurs with withdrawal from opioids, as well as changes in the brain that drive a craving for opioids. A surgically implantable VNS has been approved by the Food and Drug Administration (FDA) for the treatment of both epilepsy and severe depression. Studies have shown that VNS stimulation is helpful for both conditions. Researchers are using a non-invasive hand-held VNS device made by a company called ElectroCore. It is applied directly to the neck and does not require surgery. It is approved in Europe for the treatment of epilepsy, anxiety, depression, headaches, and other conditions, and in the US by the FDA for the treatment of headaches. Investigators have studied its use at Emory for PTSD and have found it to be well tolerated and there have been no adverse events or untoward effects with the device. The research team conducted two initial studies in patients with OUDs and found that it was safe and that it reduced opioid craving and withdrawal as well as blocking the sympathetic (adrenaline) response to withdrawal. It has not yet been approved in the US by the FDA for the treatment of OUDs and is considered investigational in this study.

This study will enroll individuals that have been diagnosed with Opioid Use Disorder (OUD). The main purpose of this study is to look at the effects of VNS on behavior as well as the body and brain's responses to craving in patients with OUDs. Study procedures include a screening, mental health assessment, medical assessment, lab work, brain imaging (MRI and PET), and a follow-up call. It is possible that participants may not have brain imaging (MRI and PET) during the study. The study will be completed in around a week depending on the scheduling of the MRI visit. This might be completed during the inpatient stay or could be a separate visit. The research team will also plan to call and follow up with participants 1-3 months after the inpatient stay.

Conditions

Withdrawal Symptoms; Opioid Use Disorder; Opioid Use

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Transcutaneous Cervical Vagal Nerve Stimulation Device

Stimulation with the tcVNS

Group Type: EXPERIMENTAL

Transcutaneous Cervical Vagal Nerve Stimulation

Intervention Type: 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).

[F-18]Fallypride

Intervention Type: DRUG

\[F-18\]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.

Sham Stimulation Device

Stimulation with the sham device.

Group Type: SHAM_COMPARATOR

Sham Stimulation

Intervention Type: 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.

[F-18]Fallypride

Intervention Type: DRUG

\[F-18\]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.

Interventions

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).

Intervention Type: 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.

Intervention Type: DEVICE

[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.

Intervention Type: DRUG

Other Intervention Names

tcVNS; Sham stimulation of vagus nerve; Radiolabeled material

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

James Douglas Bremner

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

James D Bremner, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University Clinical Research Network

Atlanta, Georgia, United States

Site Status: RECRUITING

Health Sciences Research Building

Atlanta, Georgia, United States

Site Status: NOT_YET_RECRUITING

Rollins School of Public Health

Atlanta, Georgia, United States

Site Status: RECRUITING

12 Executive Park Drive

Atlanta, Georgia, United States

Site Status: RECRUITING

Emory Univeristy

Atlanta, Georgia, United States

Site Status: RECRUITING

Georgia Institute of Technology

Atlanta, Georgia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

James D Bremner, MD

Role: CONTACT

jdbremn@emory.edu

404-712-9569

Other Identifiers

4UH3DA048502

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00005360

Identifier Type: -

Identifier Source: org_study_id