Non-Invasive Vagal Nerve Stimulation in Opioid Use Disorders (nVNS in OUDs)

Emory University

Status and phase: Completed; Phase 3

Conditions: Substance Withdrawal; Opioid-use Disorder; Substance Abuse, Intravenous; Substance Use Disorders; Substance-Related Disorders; Opioid Use; Substance Abuse; Opioid Use Disorder, Severe

Treatments: Drug: Oxygen (15-O) Water; Device: Non invasive VN stimulation (nVNS); Device: Sham Stimulation

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04556552

UG3DA048502 (U.S. NIH Grant/Contract)

IRB00117320

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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20 participants in 2 patient groups

Active non-invasive Vagal nerve stimulation (VNS)

Experimental group

Description:

Active non-invasive Vagal Nerve Stimulation (nVNS) with opioid cues.

Treatment:

Drug: Oxygen (15-O) Water

Device: Non invasive VN stimulation (nVNS)

Sham stimulation

Sham Comparator group

Description:

Sham stimulation of vagus with opioid cues

Treatment:

Drug: Oxygen (15-O) Water

Device: Sham Stimulation