A Study of New Treatment for Excessive Alcohol Users by Electric Stimulation of Nerves Around Ear
Condition: Alcohol Use Disorder
MeSH terms: Alcoholism
Study type: Interventional

Summary: 
      Alcohol Use Disorders (AUD's) are a major health and social problem. Relapse is a rule rather
      than an exception in alcohol dependence, leading to poor outcomes. Craving are frequently
      associated with relapse. Keeping in mind the high burden of disease due to AUD, limited
      efficacy of available treatment modalities it is important to study new treatment modalities.
      Vagus nerve stimulation (VNS) is a promising neuromodulation technique with robust evidence
      in epilepsy and treatment-resistant depression. fMRI studies show that transcutaneous VNS
      (tVNS) replicates most of the biological effects of VNS with an additional advantage of being
      non-invasive. Percutaneous Electrical Neural Field Stimulation (PENFS) of auricular branch of
      vagus nerve is a variant of tVNS which has shown promise in the treatment of opioid
      withdrawal. The efficacy of PENFS has been evaluated in AUDs in only handful of studies.

      I propose to employ a double-blind randomized sham-controlled trial where 40 subjects with
      AUD will be randomized to 2 groups, with 1 group receiving 'Active' auricular PENFS, and
      another group receiving bilateral 'sham' auricular PENFS.

      Assessments will be carried out at baseline and after 15 days of advent of PENFS on tasks to
      assess craving, along with neurohemodynamic changes on functional Magnetic Resonance Image
      (fMRI). Follow up of patients will be done till the first relapse or till 3 months after the
      post evaluation, whichever is earlier.

      The investigator's hypotheses are:

        1. Active PENFS will lead to significantly greater improvement in subjective craving and
           drinking-related outcomes as compared to sham PENFS in patients with AUD over the
           follow-up period of 3 months.

        2. Active PENFS will produce a significantly differential Blood Oxygen Level Dependent
           (BOLD) activation-deactivation pattern of brain regions (greater activation of
           dorsolateral prefrontal cortex and anterior cingulate cortex and along with deactivation
           of insular cortex) associated with craving during a cue-induction paradigm as compared
           to sham PENFS in patients with AUD.

        3. Active PENFS will result in a significant differential change in resting-state
           functional connectivity (fMRI measured) within and between addiction-related neural
           networks as compared to sham PENFS as evaluated with a resting state fMRI analysis in
           patients with AUD.
    

Detailed description: 
      Patients will be recruited into the study after obtaining informed consent. The intervention
      will be started after completion of detoxification, which will be done with Lorazepam using a
      front-loading regimen and a drug washout period of 5 half-lives (approx. 3 days) will be
      given so as not to interfere with the stimulation. Amitriptyline 12.5-25mg will be used as
      rescue medication for sleep difficulty. All subjects will receive psychosocial interventions
      related to craving management and relapse prevention as per treatment as usual but will not
      be prescribed any anti-craving agents during the period of the study.The Drug Relief V 2.0
      device will be installed after the detoxification and baseline fMRI scan. After installation,
      it will automatically provide neurostimulation at regular interval. It will be in situ for
      the next 15 days. After that, it will be removed temporarily for follow-up fMRI
      scanning.After completion of scanning a new device will be provided. The current research
      study will follow standard auricular PENFS procedures with established safety. The battery of
      the device will last for 15 days. Study subjects will be required to visit NIMHANS (National
      Institute of mental health and neurosciences) every 15 days to replace the old device for a
      new one. Till 3 months, all the devices will be provided free of costPatients will be
      followed up as usual on an outpatient basis, and the recent pattern of alcohol use will be
      inquired into. The follow-up will be done until the patient has a relapse or a maximum period
      of three months, whichever is earlier.
    

Intervention name(s): Drug Relief V(version) 2.0 Auricular Percutaneous Electrical Neural Field Stimulation (PENFS)
Intervention type(s): Device
Intervention description(s): This is a Small electronic circuit board with a minimal number of electronic components in it, which is powered by three zinc-air batteries. Each battery consists of 1.4v of charge. From this charge, the circuit produces a maximum voltage of 3.4V under no load condition.
The produced Voltage is driven as output by using the three stimulation wires, and the fourth insulated wire acts as a ground. The wires are Bio-compatible and do not have any impact when in contact with the human skin. The wire is attached with a needle to transfer the produced voltage into the nerves of the human ear. The sterilized needle (Titanium) is attached at the end of the wire through a snap fit ring. All the materials used are gone through necessary safety and performance testing including bio-compatibility and sterility testing, wherever necessary.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized (permuted block randomization, fixed), Parallel Group, Placebo Controlled Trial.
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Alcohol dependence; Peripheral electrical nerve field stimulation (PENFS); Auricular nerve stimulation; Vagus nerve stimulation; relapse prevention