Clinical trial NCT05834478: Non-invasive Vagal Nerve Stimulation in Opioid Use Disorders UH3
Official title: Non-invasive Vagal Nerve Stimulation in Opioid Use Disorders UH3
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Withdrawal Symptoms
Opioid Use Disorder
Opioid Use
Keywords: Non-invasive Vagal Nerve Stimulation
Vagus nerve
vagus nerve stimulation
OUD
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2023-04-28
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Peak Subjective Opiate Withdrawal Scale (SOWS) Score
timeFrame: Day 2, Day 3
measure: Safety of tcVNS use
timeFrame: Up to 7 days after study initiation
Secondary outcomes:
measure: Study retention
timeFrame: Baseline, Up to 10 days after study initiation
measure: Treatment adherence
timeFrame: 3 months
measure: Change in brain dopamine D1 and D2/3 receptor regional binding potentials
timeFrame: Day 2, Day 3
measure: Change in heart rate
timeFrame: Baseline, Day 2, Day 3
measure: Change in inflammatory biomarkers
timeFrame: 15 minutes before stress and up to 180 minutes post-stress
measure: Change in catecholamines concentration
timeFrame: Baseline, Day 2, Day 3
measure: Squares analysis of SOWS score
timeFrame: Day 1, Day 7
measure: Time to Rescue Medication
timeFrame: Up to 7 days after study initiation
measure: Change in Peak Clinical Opiate Withdrawal Scale (COWS) Scores
timeFrame: Day 2, Day 3
measure: Transition to MOUD Treatment or Behavioral Management
timeFrame: Up to 7 days after study initiation
measure: Change in Brain-derived Neurotrophic Factor (BDNF)
timeFrame: 5 minutes before stress and up to 180 minutes post-stress
measure: Change in Calcium-binding Protein B (S100B)
timeFrame: 5 minutes before stress and up to 180 minutes post-stress
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Clinical Research Network
state: Georgia
city: Atlanta
country: United States
facility: Health Sciences Research Building
state: Georgia
city: Atlanta
country: United States
facility: Rollins School of Public Health
state: Georgia
city: Atlanta
country: United States
facility: 12 Executive Park Drive
state: Georgia
city: Atlanta
country: United States
facility: Emory Univeristy
state: Georgia
city: Atlanta
country: United States
facility: Georgia Institute of Technology
state: Georgia
Study officials:
affiliation: Emory University
name: James D Bremner, MD
role: PRINCIPAL_INVESTIGATOR
References: