A Study of New Treatment for Excessive Alcohol Users by Electric Stimulation of Nerves Around Ear

NCT04106739 | Completed DMC

• 1 other identifier: CS010
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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. 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. 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. 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.

Conditions

Alcohol Use Disorder

Keywords

Alcohol dependence; Peripheral electrical nerve field stimulation (PENFS); Auricular nerve stimulation; Vagus nerve stimulation; relapse prevention

Outcome Measures

Primary Outcomes (1)

• Craving scores

  Change in craving scores measured with Penns Alcohol Craving Scale between baseline and equispaced 6 follow-ups (every 15 days) for 3 months. Scale Information: 1. Scale name: Penn Alcohol Craving Scale. It measures craving for alcohol. 2. It is a 5-item scale. Each item score range is 0 to 6. So, Scale's total score range is 0 to 30. 3. Score 0 signifies no craving and score 30 signifies maximum craving. 4. There is no subscale.

  90 days

Secondary Outcomes (1)

• Cue-induced craving resting state fMRI

  14 days

Study Arms (2)

Active Arm

ACTIVE COMPARATOR

Active arm: Auricular Percutaneous Electrical Neural Field Stimulation (PENFS) device will stimulate the outer auditory canal. It will deliver with a pulse width of 500 ms. The stimulation frequency pattern is 1.12Hz(hertz), 2.24Hz,4.56Hz, 9.12Hz, 100Hz then 9.12Hz, 4.56Hz,2.28Hz,1.12Hz. This cycle will keep on continuing. An input voltage will be 4.2V(volt).

Device: Drug Relief V(version) 2.0 Auricular Percutaneous Electrical Neural Field Stimulation (PENFS)

Sham Arm

SHAM COMPARATOR

Sham arm: Auricular Percutaneous Electrical Neural Field Stimulation (PENFS) device will stimulate centre of the left ear lobe to a pulse width of 500 ms at same pattern of stimulation frequency mentioned in active PENFS with an input voltage of 4.2V

Device: Drug Relief V(version) 2.0 Auricular Percutaneous Electrical Neural Field Stimulation (PENFS)

Interventions

Drug Relief V(version) 2.0 Auricular Percutaneous Electrical Neural Field Stimulation (PENFS) DEVICE

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.

Active Arm; Sham Arm

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: 1. To restrict number of variables in the study. 2. Prevalence/Availability of women with AUD is low.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Male gender.
• Age not less than 18 years and not more than 50 years.
• At least, moderately severe AUD as ascertained by a score above 16 in Severity of Alcohol dependence questionnaire (SADQ).
• Right-handedness as assessed with Edinburgh Handedness Inventory.
• Informed consent and willingness to come for regular follow-ups (once every two weeks) for three months after recruitment in the study.

You may not qualify if:

• Any diagnosis except alcohol dependence syndrome/ Tobacco dependence syndrome (to apply MINI(Mini International Neuropsychiatric Interview) screen).
• Contra-indications precluding device use-
• 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
• Left/ mixed handedness
• Contraindications to MRI

Sponsors & Collaborators

• DyAnsys, Inc.: lead

Study Sites (1)

National Institute of Mental Health and Neuro sciences(NIMHANS)

Bengaluru, Karnataka, 560029, India

Location

Related Publications (18)

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MeSH Terms

Conditions

Alcoholism

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Diptadhi Mukherjee, MBBS,DM

  National Institute of Mental Health and Neuro Sciences (NIMHANS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized (permuted block randomization, fixed), Parallel Group, Placebo Controlled Trial.

Study Record Dates

• First Submitted: September 25, 2019
• First Posted: September 27, 2019
• Study Start: October 20, 2019
• Primary Completion: December 27, 2021
• Study Completion: December 27, 2021
• Last Updated: March 3, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)