Temporal Interference Neurostimulation and Addiction

Overview

This project aims to develop a line of research using new non-invasive neurostimulation technology to treat adults with opioid use disorders (OUDs). In the short term, the investigators aim to identify novel target brain regions for neurostimulation treatment and characterize their effects behaviorally and neurally. In the longer term, investigators aim to use these preliminary data to justify NIH sponsored clinical trials to apply transcranial direct current stimulation and non-invasive deep brain stimulation to these areas to partially or completely disrupt addiction.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Single (Participant)
  • Study Primary Completion Date: May 2027

Detailed Description

The investigators hypothesize that temporal interference non-invasive deep brain stimulation (TI-NDBS) will be well tolerated and effective at manipulating brain activity and reducing drug cravings. The investigators will investigate whether stimulation with a mild current from temporal interference non-invasive deep brain stimulation (TI-NDBS) to the Anterior Cingulate Cortex (ACC), the anterior insula (AI), or the nucleus accumbens (NAcc) will reduce nicotine craving and seeking. The TI-NDBS is similar to the traditional transcranial direct current stimulation (tDCS), a method approved for use in a number of other studies. Other studies have shown there have been some effects of reducing craving with tDCS, however, tDCS cannot stimulate structures such as the ACC very effectively because tDCS cannot stimulate deeper brain regions. Thus, the Specific Aim ultimately will compare TI-NDBS with tDCS and sham stimulation. The study is broken up into four phases. The first two will involve device feasibility and identifying the best locations for the electrodes to be placed. In the third phase, the investigators will compare TI-NDBS with sham stimulation. In the fourth phase, the investigators will compare TI-NDBS with sham stimulation and with tDCS.

Interventions

  • Device: Active TI-NDBS
    • In the active TI-NDBS condition, subjects will receive stimulation for 60 minutes applied to the brain through scalp electrodes. There will be a maximum of 2 mA per electrode pair and no single region will receive more than 2 mA because the currents will be administered to distinct regions. At the beginning of each stimulation period, the current will increase slowly at a constant rate for 30 seconds until it reaches the appropriate intensity. At the end of the stimulation, the current will decrease slowly for 30 seconds until it reaches zero.
  • Other: Sham TI-NDBS
    • This is the control condition in which participants will receive sham stimulation for 60 minutes.
  • Device: tDCS
    • This is a well established method of brain stimulation and will be used to compare against the efficacy of TI-NDBS in the reduction of nicotine craving and inhalation. Participants will receive stimulation for 60 minutes.

Arms, Groups and Cohorts

  • Experimental: Phase 3 Active TI-NDBS
    • Participants assigned to this condition will receive active temporal interference non-invasive deep brain stimulation. Participants will receive stimulation for 60 minutes on one day.
  • Sham Comparator: Phase 3 Sham TI-NDBS
    • Participants assigned to this condition will receive sham temporal interference non-invasive deep brain stimulation, in which they will have electrodes attached to the scalp but the device is only turned on for a few seconds.
  • Active Comparator: Phase 4 Traditional tDCS
    • Participants assigned to this condition will receive traditional transcranial direct current stimulation for 60 minutes for 5 days.
  • Experimental: Phase 4 TI-NDBS
    • Participants assigned to this condition will receive active temporal interference non-invasive deep brain stimulation for 60 minutes for 5 days and will be compared to sham stimulation and tDCS.
  • Sham Comparator: Phase 4 Sham stimulation
    • Participants assigned to this condition will receive sham temporal interference non-invasive deep brain stimulation, in which they will have electrodes attached to the scalp but the device is only turned on for a few seconds. Participants will be in the scanner for 60 minutes for 5 days. This will be used as the control condition and compared with TI-NDBS and tDCS.

Clinical Trial Outcome Measures

Primary Measures

  • Change in Nicotine craving
    • Time Frame: Within the first year of testing TI-NDBS in nicotine smokers.
    • The investigators predict that TI-NDBS will outperform sham stimulation at an overall change in smoking and cigarette craving, which in turn will outperform sham stimulation. The investigators will sum the total inhaled nicotine vapor volume in liters over the 60 minute session and perform pairwise t-tests to determine if total drug intake is lower with TI-NDBS vs tDCS. Also, the investigators will average the self reported craving levels on a Likert scale across each subject during the 60 minute session, and the investigators will perform pairwise tests to determine if stimulation lowers self reported craving.
  • Change in Nicotine craving due to TI-NDBS compared to tDCS
    • Time Frame: 1 year after the first primary outcome.
    • The investigators predict that TI-NDBS will outperform tDCS at an overall change in smoking and cigarette craving, which in turn will outperform sham stimulation. The investigators will sum the total inhaled nicotine vapor volume in liters over the 60 minute session and perform pairwise t-tests to determine if total drug intake is lower with one of the stimulation groups vs. sham. Also, the investigators will average the self reported craving levels on a Likert scale across each subject during the 60 minute session, and the investigators will perform pairwise tests to determine if stimulation lowers self reported craving.

Participating in This Clinical Trial

Inclusion Criteria

  • Must be between the ages of 18 and 40, must have at least 6th grade education, and the ability to speak and read English, must smoke at least 3/4 of a pack of cigarettes per day, must have phone with internet access. Exclusion Criteria:

  • if they are on psychotropic medications for ADHD, other mental illness or medication for cancer, epilepsy (i.e. individuals with any history of seizure disorder), migraines, or other neurological syndromes, or AIDs (which can cause cognitive deficits (Watkins & Treisman, 2015), history of head trauma, history of cognitive impairments, metal implants in the head or under the scalp, personal experiences consistent with symptoms of psychosis (i.e. mind or body being secretly controlled, special powers, seeing or hearing things that aren't really there). – Subjects will be excluded if they do not meet fMRI safety screening criteria (i.e. metal implants in their body, tattoo on head or neck, permanent jewelry, etc.) or if a participant uses an IUD for birth control they will be excluded unless the subject can document the model of the IUD and we can verify its safety for the MRI environment. Pregnancy should be self-reported, and a pregnancy test will not be administered. Participants must also weigh less than 440 lbs. – History of holes bored into skull or known fissures in cranial bones – Presence of pacemakers

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 40 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Indiana University
  • Collaborator
    • Indiana University School of Medicine
  • Provider of Information About this Clinical Study
    • Principal Investigator: Joshua Brown, PHD, Professor, Psychological and Brain Sciences – Indiana University
  • Overall Contact(s)
    • Joshua Brown, PhD, 812-855-9282, jwmbrown@indiana.edu

References

Fregni F, Liguori P, Fecteau S, Nitsche MA, Pascual-Leone A, Boggio PS. Cortical stimulation of the prefrontal cortex with transcranial direct current stimulation reduces cue-provoked smoking craving: a randomized, sham-controlled study. J Clin Psychiatry. 2008 Jan;69(1):32-40. doi: 10.4088/jcp.v69n0105.

Grossman N, Bono D, Dedic N, Kodandaramaiah SB, Rudenko A, Suk HJ, Cassara AM, Neufeld E, Kuster N, Tsai LH, Pascual-Leone A, Boyden ES. Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields. Cell. 2017 Jun 1;169(6):1029-1041.e16. doi: 10.1016/j.cell.2017.05.024.

Fecteau S, Agosta S, Hone-Blanchet A, Fregni F, Boggio P, Ciraulo D, Pascual-Leone A. Modulation of smoking and decision-making behaviors with transcranial direct current stimulation in tobacco smokers: a preliminary study. Drug Alcohol Depend. 2014 Jul 1;140:78-84. doi: 10.1016/j.drugalcdep.2014.03.036. Epub 2014 Apr 16.

Hulvershorn LA, Hummer TA, Fukunaga R, Leibenluft E, Finn P, Cyders MA, Anand A, Overhage L, Dir A, Brown J. Neural activation during risky decision-making in youth at high risk for substance use disorders. Psychiatry Res. 2015 Aug 30;233(2):102-11. doi: 10.1016/j.pscychresns.2015.05.007. Epub 2015 May 21.

Wing VC, Barr MS, Wass CE, Lipsman N, Lozano AM, Daskalakis ZJ, George TP. Brain stimulation methods to treat tobacco addiction. Brain Stimul. 2013 May;6(3):221-30. doi: 10.1016/j.brs.2012.06.008. Epub 2012 Jul 9.

Velez de Mendizabal N, Jones DR, Jahn A, Bies RR, Brown JW. Nicotine and cotinine exposure from electronic cigarettes: a population approach. Clin Pharmacokinet. 2015 Jun;54(6):615-26. doi: 10.1007/s40262-014-0221-7.

Naqvi NH, Rudrauf D, Damasio H, Bechara A. Damage to the insula disrupts addiction to cigarette smoking. Science. 2007 Jan 26;315(5811):531-4. doi: 10.1126/science.1135926.

Naqvi NH, Gaznick N, Tranel D, Bechara A. The insula: a critical neural substrate for craving and drug seeking under conflict and risk. Ann N Y Acad Sci. 2014 May;1316:53-70. doi: 10.1111/nyas.12415. Epub 2014 Apr 1.

Muller UJ, Sturm V, Voges J, Heinze HJ, Galazky I, Heldmann M, Scheich H, Bogerts B. Successful treatment of chronic resistant alcoholism by deep brain stimulation of nucleus accumbens: first experience with three cases. Pharmacopsychiatry. 2009 Nov;42(6):288-91. doi: 10.1055/s-0029-1233489. Epub 2009 Nov 18. No abstract available.

Craig AD. How do you feel? Interoception: the sense of the physiological condition of the body. Nat Rev Neurosci. 2002 Aug;3(8):655-66. doi: 10.1038/nrn894.

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