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
Intervention: Non invasive VN stimulation (nVNS); Oxygen (15-O) Water; Sham Stimulation
Intervention description: 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.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: nVNS versus sham stimulation
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: sham stimulation
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: opioid use disorder; vagus nerve; vagal nerve; neuromodulation; vagus nerve stimulation; OUD

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.
    

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