Non-Invasive Vagal Nerve Stimulation in Opioid Use Disorders

Phase 3

Completed

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

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

Registration Number: NCT04556552

Lead Sponsor: Emory University

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

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

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active non-invasive Vagal nerve stimulation (VNS)	Non invasive VN stimulation (nVNS)	Active non-invasive Vagal Nerve Stimulation (nVNS) with opioid cues.
Sham stimulation	Sham Stimulation	Sham stimulation of vagus with opioid cues
Active non-invasive Vagal nerve stimulation (VNS)	Oxygen (15-O) Water	Active non-invasive Vagal Nerve Stimulation (nVNS) with opioid cues.
Sham stimulation	Oxygen (15-O) Water	Sham stimulation of vagus with opioid cues

Primary Outcome Measures

Name	Time	Method
Opioid Craving Using Visual Analogue Scale	Baseline, 5 minutes post-intervention	Opioid craving will be measured based on Visual Analogue Scale (VAS) VAS consist in 10-point lines anchored with "not at all" on one end and "extremely" on the other where participants report the extent to which they felt any craving for opiates, severity of withdrawal symptoms, and the extent to which the study intervention has helped to ease the cravings. Total possible score ranges from 0 to100, with 100 correlating with worse study outcome.
Heart Rate (HR)	Baseline, two minutes post-intervention	Heart rate will be measured after cue. Decreased HR correlates with better outcome.
Pre-ejection Period (PEP)	Baseline, 2 minutes post-intervention	Pre-ejection Period (PEP) is a marker of cardiac sympathetic tone that is increased with blocked sympathetic function. Higher PEP correlates with better outcome.
Photoplethysmography (PPG) Amplitude	Baseline, 2 minutes post-intervention	Photoplethysmography (PPG) amplitude reflects vasoconstriction in figure blood vessel. PPG amplitude is increased with blocked sympathetic tone and higher PPG correlates with better outcome.
Brain Blood Flow in the Anterior Cingulate With VNS Paired With Opioid Use Videos	Baseline, 2 minutes post-intervention	Brain blood flow measured with Positron Emission Tomography (PET) and radiolabeled water at baseline and 2 min post-intervention during viewing of neutral videos and with active and Sham VNS stimulation paired with opioid use videos. Brain blood flow was measured in mL per 100 g of tissue per minute (mL/100g/min) normalized to a reference of 50 ml/100 g of tissue per minute.

Secondary Outcome Measures

Name	Time	Method
Levels of Interleukin 6 (IL-6)	Baseline, 2 minutes post-intervention	IL-6 is an inflammatory marker. Reduced levels of IL-6 correlate with better outcome.