Clinical trial NCT04556552: Non-Invasive Vagal Nerve Stimulation in Opioid Use Disorders
Official title: Non-Invasive Vagal Nerve Stimulation in Opioid Use Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Substance-Related Disorders
Substance Use Disorders
Substance Abuse, Intravenous
Substance Withdrawal
Substance Abuse
Opioid-use Disorder
Opioid Use Disorder, Severe
Opioid Use
Keywords: opioid use disorder
vagus nerve
vagal nerve
neuromodulation
vagus nerve stimulation
OUD
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
name: City University of New York
name: Georgia Institute of Technology
First posted: 2020-09-21
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: nVNS versus sham stimulation
Primary purpose: TREATMENT

Brief summary: Subjects in this study will be patients with opioid use disorders (OUDs) based on DSM-5 criteria recruited from the greater Atlanta metropolitan region. Recruitment will be from treatment programs in the greater Atlanta Metropolitan Region including the DeKalb Community Service Board residential, detoxification and other treatment programs which with over 30,000 patient visits per year represents the largest treatment program in one of two urban counties in greater Atlanta.

This trial involves a second phase after completing an exploratory study in 20 patients with OUDs to assess different timing parameters of nVNS effects on sympathetic measures and symptoms of craving, as well as modelling to verify and iteratively refine the methods for vagal nerve stimulation. The investigators in this trial will then apply nVNS comparing active (N=10) to sham (N=10) in OUD patients recently started on medication, looking at opioid craving, brain functional response with HR-PET, and cardiovascular and inflammatory biomarker responses to imagery-induced opioid drug craving.

Detailed description: Subjects in this study will be patients with opioid use disorders (OUDs) based on DSM-5 criteria recruited from the greater Atlanta metropolitan region. The metropolitan Atlanta area has about 2,623,744 persons age 12 or older. According to the Substance Abuse and Mental Health Services Administration (SAMHSA), 109,777 (4.18%) have non-medical use of prescription pain relievers, and 48,302 are estimated to have an opioid use disorder. This DSMP describes the UG3 phase which will study patients with OUDs early in the course of treatment. The Go-No Go criteria listed below have to be met to proceed to the UH3. Recruitment will be from treatment programs in the greater Atlanta Metropolitan Region including the DeKalb Community Service Board residential, detoxification and other treatment programs which with over 30,000 patient visits per year represents the largest treatment program in one of two urban counties in greater Atlanta.

The first UG3 phase will involve an exploratory study in 20 patients with OUDs to assess different timing parameters of nVNS effects on sympathetic measures and symptoms of craving, as well as modelling to verify and iteratively refine our methods for vagal nerve stimulation. The investigators in this trial will then apply nVNS in a pilot study comparing active (N=10) to sham (N=10) in OUD patients recently started on medication, looking at opioid craving, brain functional response with HR-PET, and cardiovascular and inflammatory biomarker responses to imagery-induced opioid drug craving. Brain function will be measured with high resolution positron emission tomography (HR-PET), autonomic function with wearable sensing devices, and biomarkers will be measured in blood, with an assessment of a broad range of stress responsive sympathetic, hormonal and immune markers.

Eligibility criteria: Inclusion Criteria:

* Inclusion Criteria:

Subjects aged 18 and over who meet criteria for OUDs based on the Structured Clinical Interview for DSM-5 (SCID) interview and are stable on medication treatment.

Exclusion Criteria:

1. Positive pregnancy test
2. Meningitis
3. Traumatic brain injury
4. Neurological disorder or organic mental disorder
5. History of loss of consciousness greater than one minute
6. Current pregnancy or breastfeeding for women
7. Current or lifetime history of schizophrenia, schizoaffective disorder, or bulimia, based on the SCID
8. A history of serious medical or neurological illness, such as cardiovascular, gastrointestinal, hepatic, renal, neurologic or other systemic illness
9. Evidence of a major medical or neurological illness that is based on the clinical judgment of the study psychiatrist
10. Active implantable device (i.e. pacemaker)
11. Carotid atherosclerosis
12. Cervical vagotomy

Primary outcomes:
measure: Opioid Craving Using Visual Analogue Scale
timeFrame: Baseline, 5 minutes post-intervention
measure: Heart Rate (HR)
timeFrame: Baseline, two minutes post-intervention
measure: Pre-ejection Period (PEP)
timeFrame: Baseline, 2 minutes post-intervention
measure: Photoplethysmography (PPG) Amplitude
timeFrame: Baseline, 2 minutes post-intervention
measure: Brain Blood Flow in the Anterior Cingulate With VNS Paired With Opioid Use Videos
timeFrame: Baseline, 2 minutes post-intervention
Secondary outcomes:
measure: Levels of Interleukin 6 (IL-6)
timeFrame: Baseline, 2 minutes post-intervention
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
Study officials:
affiliation: Emory University
name: J Douglas Bremner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gazi AH, Harrison AB, Lambert TP, Obideen M, Alavi P, Murrah N, Shallenberger L, Driggers EG, Ortega RA, Washington BP, Walton KM, Welsh JW, Vaccarino V, Shah AJ, Tang YL, Gupta R, Back SE, Inan OT, Bremner JD. Transcutaneous cervical vagus nerve stimulation reduces behavioral and physiological manifestations of withdrawal in patients with opioid use disorder: A double-blind, randomized, sham-controlled pilot study. Brain Stimul. 2022 Sep-Oct;15(5):1206-1214. doi: 10.1016/j.brs.2022.08.017. Epub 2022 Aug 27.