Clinical trial NCT04106739: A Study of New Treatment for Excessive Alcohol Users by Electric Stimulation of Nerves Around Ear
Official title: Auricular Percutaneous Electrical Neural Field Stimulation in Short-Term Treatment of Alcohol Dependence- Neurohaemodynamic Correlates and Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alcohol Use Disorder
Keywords: Alcohol dependence
Peripheral electrical nerve field stimulation (PENFS)
Auricular nerve stimulation
Vagus nerve stimulation
relapse prevention
Lead sponsor: DyAnsys, Inc.
Sponsor class: INDUSTRY
First posted: 2019-09-27
Enrollment: 44
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized (permuted block randomization, fixed), Parallel Group, Placebo Controlled Trial.
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of Alcohol use disorder (AUD) as per DSM(Diagnostic and Statistical Manual of Mental Disorders)-5 by two psychiatrists working in the department of psychiatry NIMHANS.
2. Male gender.
3. Age not less than 18 years and not more than 50 years.
4. At least, moderately severe AUD as ascertained by a score above 16 in Severity of Alcohol dependence questionnaire (SADQ).
5. Right-handedness as assessed with Edinburgh Handedness Inventory.
6. Informed consent and willingness to come for regular follow-ups (once every two weeks) for three months after recruitment in the study.

Exclusion Criteria:

1. Any diagnosis except alcohol dependence syndrome/ Tobacco dependence syndrome (to apply MINI(Mini International Neuropsychiatric Interview) screen).
2. Contra-indications precluding device use-

   2.1 patient with cardiac implants or similar biomedical implants, 2.2 during pregnancy unless medically advised, 2.3 patient with haemophilia 2.4 skin pathology 2.5 patient with diminished mental capability or physical competence about the handling of the device
3. Left/ mixed handedness
4. Contraindications to MRI

Primary outcomes:
measure: Craving scores
timeFrame: 90 days
Secondary outcomes:
measure: Cue-induced craving resting state fMRI
timeFrame: 14 days
Other outcomes:
Locations:
city: Bengaluru
country: India
facility: National Institute of Mental Health and Neuro sciences(NIMHANS)
state: Karnataka
Study officials:
affiliation: National Institute of Mental Health and Neuro Sciences (NIMHANS)
name: Diptadhi Mukherjee, MBBS,DM
role: PRINCIPAL_INVESTIGATOR
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