Non-invasive Vagal Nerve Stimulation in Opioid Use Disorders UH3

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство 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-stimulati
• Устройство 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.
• Препарат [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.

Первичные конечные точки

• Change in Peak Subjective Opiate Withdrawal Scale (SOWS) Score [Срок оценки: Day 2, Day 3]
• Safety of tcVNS use [Срок оценки: Up to 7 days after study initiation]

Вторичные конечные точки (12)

• Study retention [Срок оценки: Baseline, Up to 10 days after study initiation]
• Treatment adherence [Срок оценки: 3 months]
• Change in brain dopamine D1 and D2/3 receptor regional binding potentials [Срок оценки: Day 2, Day 3]
• Change in heart rate [Срок оценки: Baseline, Day 2, Day 3]
• Change in inflammatory biomarkers [Срок оценки: 15 minutes before stress and up to 180 minutes post-stress]
• Change in catecholamines concentration [Срок оценки: Baseline, Day 2, Day 3]
• Squares analysis of SOWS score [Срок оценки: Day 1, Day 7]
• Time to Rescue Medication [Срок оценки: Up to 7 days after study initiation]
• Change in Peak Clinical Opiate Withdrawal Scale (COWS) Scores [Срок оценки: Day 2, Day 3]
• Transition to MOUD Treatment or Behavioral Management [Срок оценки: Up to 7 days after study initiation]
• Change in Brain-derived Neurotrophic Factor (BDNF) [Срок оценки: 5 minutes before stress and up to 180 minutes post-stress]
• Change in Calcium-binding Protein B (S100B) [Срок оценки: 5 minutes before stress and up to 180 minutes post-stress]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 6 центров

• Emory University Clinical Research Network — Atlanta
• Health Sciences Research Building — Atlanta
• Rollins School of Public Health — Atlanta
• 12 Executive Park Drive — Atlanta
• Emory University — Atlanta
• Georgia Institute of Technology — Atlanta

Идентификаторы

NCT: NCT05834478 · STUDY00005360 · 4UH3DA048502 · 2025P012727

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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