Non-Invasive Vagal Nerve Stimulation in Opioid Use Disorders
Condition: Substance-Related Disorders; Substance Use Disorders; Substance Abuse, Intravenous; Substance Withdrawal; Substance Abuse; Opioid-use Disorder; Opioid Use Disorder, Severe; Opioid Use
MeSH terms: Substance-Related Disorders; Opioid-Related Disorders; Substance Abuse, Intravenous
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Non invasive VN stimulation (nVNS); Oxygen (15-O) Water; Sham Stimulation
Intervention type(s): Device; Drug; Device
Intervention description(s): Stimulation of vagus nerve with active device. Participants will be administered nVNS using the electroCore GammaCore-S non-invasive VNS device. The intensity of the stimulus will be adjusted by the user, to the maximum tolerable level to ensure nVNS without causing excessive pain, the burst frequency to 5 kHz, and the envelope frequency to 25 Hz.
The duration of delivery will be 2 minutes, and the beginning will coincide with initiation of acquisition of the HR-PET scan which will be 90 seconds in duration; following an additional 8 minutes, a second VNS delivery will be administered, in conjunction with which another scan will be obtained.; Injection of radiolabelled water. H2[15-O] is a radioactive material. Each patient will have eight H2[15-O] blood flow scans. For each O-15 water scan 20 mCi of H2[15O] will be injected as an intravenous bolus.; Sham stimulation of vagus during opioid cue exposure. Each subject in the "SHAM" group will undergo the action of administering the intervention, but the device will be programmed such that the stimulation will not activate the vagus nerve.
Other intervention name(s): radiolabelled water
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: nVNS versus sham stimulation
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: opioid use disorder; vagus nerve; vagal nerve; neuromodulation; vagus nerve stimulation; OUD