A Study of New Treatment for Excessive Alcohol Users by Electric Stimulation of Nerves Around Ear
Auricular Percutaneous Electrical Neural Field Stimulation in Short-Term Treatment of Alcohol Dependence- Neurohaemodynamic Correlates and Feasibility Study
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:
- 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.
- 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.
- 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.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Ikke anvendelig
Kontakter og lokationer
Studiesteder
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Karnataka
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Bengaluru, Karnataka, Indien, 560029
- National Institute of Mental Health and Neuro sciences(NIMHANS)
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- 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.
Exclusion Criteria:
- Any diagnosis except alcohol dependence syndrome/ Tobacco dependence syndrome (to apply MINI(Mini International Neuropsychiatric Interview) screen).
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
- Left/ mixed handedness
- Contraindications to MRI
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Dobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Aktiv komparator: Active Arm
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).
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Enhed: Drug Relief V(version) 2.0 Auricular Percutaneous Electrical Neural Field Stimulation (PENFS)
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. |
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Sham-komparator: Sham Arm
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
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Enhed: Drug Relief V(version) 2.0 Auricular Percutaneous Electrical Neural Field Stimulation (PENFS)
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. |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Craving scores
Tidsramme: 90 days
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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:
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90 days
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Cue-induced craving resting state fMRI
Tidsramme: 14 days
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Change in Cue-induced craving as measured by the VICE protocol 6-minute Visual Image Induced Craving for Ethanol (VICE) paradigm fMRI and resting state fMRI neurohemodynamic changes in the dorsolateral prefrontal cortex, anterior cingulate cortex (ACC) and insular cortex (IC) after 14 days PENFS. Time-Points are as follows: Time 0 is on the day of recruitment. Time 1 is on Day 14 of recruitment. |
14 days
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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Diptadhi Mukherjee, MBBS,DM, National Institute of Mental Health and Neuro sciences(NIMHANS)
Publikationer og nyttige links
Generelle publikationer
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- Wang Z, Fang J, Liu J, Rong P, Jorgenson K, Park J, Lang C, Hong Y, Zhu B, Kong J. Frequency-dependent functional connectivity of the nucleus accumbens during continuous transcutaneous vagus nerve stimulation in major depressive disorder. J Psychiatr Res. 2018 Jul;102:123-131. doi: 10.1016/j.jpsychires.2017.12.018. Epub 2017 Dec 28.
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- Rehm J, Samokhvalov AV, Shield KD. Global burden of alcoholic liver diseases. J Hepatol. 2013 Jul;59(1):160-8. doi: 10.1016/j.jhep.2013.03.007. Epub 2013 Mar 16.
- Soyka M, Muller CA. Pharmacotherapy of alcoholism - an update on approved and off-label medications. Expert Opin Pharmacother. 2017 Aug;18(12):1187-1199. doi: 10.1080/14656566.2017.1349098. Epub 2017 Jul 24.
- Maisel NC, Blodgett JC, Wilbourne PL, Humphreys K, Finney JW. Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful? Addiction. 2013 Feb;108(2):275-93. doi: 10.1111/j.1360-0443.2012.04054.x. Epub 2012 Oct 17.
- Foxcroft DR, Coombes L, Wood S, Allen D, Almeida Santimano NM. Motivational interviewing for alcohol misuse in young adults. Cochrane Database Syst Rev. 2014 Aug 21;(8):CD007025. doi: 10.1002/14651858.CD007025.pub2.
- Schacht JP, Anton RF, Myrick H. Functional neuroimaging studies of alcohol cue reactivity: a quantitative meta-analysis and systematic review. Addict Biol. 2013 Jan;18(1):121-33. doi: 10.1111/j.1369-1600.2012.00464.x. Epub 2012 May 10.
- Sutherland MT, McHugh MJ, Pariyadath V, Stein EA. Resting state functional connectivity in addiction: Lessons learned and a road ahead. Neuroimage. 2012 Oct 1;62(4):2281-95. doi: 10.1016/j.neuroimage.2012.01.117. Epub 2012 Feb 1.
- Frangos E, Ellrich J, Komisaruk BR. Non-invasive Access to the Vagus Nerve Central Projections via Electrical Stimulation of the External Ear: fMRI Evidence in Humans. Brain Stimul. 2015 May-Jun;8(3):624-36. doi: 10.1016/j.brs.2014.11.018. Epub 2014 Dec 6.
- Miranda A, Taca A. Neuromodulation with percutaneous electrical nerve field stimulation is associated with reduction in signs and symptoms of opioid withdrawal: a multisite, retrospective assessment. Am J Drug Alcohol Abuse. 2018;44(1):56-63. doi: 10.1080/00952990.2017.1295459. Epub 2017 Mar 16. Erratum In: Am J Drug Alcohol Abuse. 2018;44(4):498.
- Kraus T, Hosl K, Kiess O, Schanze A, Kornhuber J, Forster C. BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation. J Neural Transm (Vienna). 2007;114(11):1485-93. doi: 10.1007/s00702-007-0755-z. Epub 2007 Jun 14.
- Davidson R. Assessment of the alcohol dependence syndrome: a review of self-report screening questionnaires. Br J Clin Psychol. 1987 Nov;26(4):243-55. doi: 10.1111/j.2044-8260.1987.tb01358.x.
- Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57.
- Stockwell T, Murphy D, Hodgson R. The severity of alcohol dependence questionnaire: its use, reliability and validity. Br J Addict. 1983 Jun;78(2):145-55. doi: 10.1111/j.1360-0443.1983.tb05502.x. No abstract available.
- James KE, Bloch DA, Lee KK, Kraemer HC, Fuller RK. An index for assessing blindness in a multi-centre clinical trial: disulfiram for alcohol cessation--a VA cooperative study. Stat Med. 1996 Jul 15;15(13):1421-34. doi: 10.1002/(SICI)1097-0258(19960715)15:133.0.CO;2-H.
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
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Nøgleord
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Andre undersøgelses-id-numre
- CS010
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