Temporal Interference Neurostimulation and Addiction

NCT04432064 | Terminated Results DMC FDA Device

• 1 other identifier: 1904451651
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nicotine Use Disorder; Substance Use Disorders

Keywords

Nicotine Addiction; Non-invasive deep brain stimulation; Substance Use Disorders

Outcome Measures

Primary Outcomes (1)

• Change in Nicotine Craving

  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. \*\*The Likert scale is 0-10, where 10 is maximum craving. The units are units on a scale.\*\* \*\*The outcome measure is computed by taking the pre-stimulation craving and subtracting the post-stimulation craving. Positive numbers indicate the degree to which the self-reported craving was reduced after the stimulation relative to before stimulation\*\*

  Each subject was asked to report their craving during the day of the session, before and after the stimulation. Approximately one hour elapsed between before and after nicotine craving measurements. The session was carried out during the daytime.

Study Arms (5)

Phase 3 Active TI-NDBS

EXPERIMENTAL

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.

Device: Active TI-NDBS

Phase 3 Sham TI-NDBS

SHAM COMPARATOR

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.

Other: Sham TI-NDBS

Phase 4 Traditional tDCS

ACTIVE COMPARATOR

Participants assigned to this condition will receive traditional transcranial direct current stimulation for 60 minutes for 5 days.

Device: tDCS

Phase 4 TI-NDBS

EXPERIMENTAL

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.

Device: Active TI-NDBS

Phase 4 Sham stimulation

SHAM COMPARATOR

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.

Other: Sham TI-NDBS

Interventions

Active TI-NDBS DEVICE

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.

Also known as: Temporal Interference Non-invasive Deep Brain Stimulation

Phase 3 Active TI-NDBS; Phase 4 TI-NDBS

Sham TI-NDBS OTHER

This is the control condition in which participants will receive sham stimulation for 60 minutes.

Phase 3 Sham TI-NDBS; Phase 4 Sham stimulation

tDCS DEVICE

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.

Phase 4 Traditional tDCS

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must be between the ages of 18 and 50, 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Indiana University: lead
• Indiana University School of Medicine: collaborator

Study Sites (1)

Indiana University

Bloomington, Indiana, 47403, United States

Location

Related Publications (10)

• 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.

  PMID: 18312035 BACKGROUND

• 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.

  PMID: 28575667 BACKGROUND

• 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.

  PMID: 24814566 BACKGROUND

• 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.

  PMID: 26071624 BACKGROUND

• 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.

  PMID: 22809824 BACKGROUND

• 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.

  PMID: 25503588 BACKGROUND

• 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.

  PMID: 17255515 BACKGROUND

• 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.

  PMID: 24690001 BACKGROUND

• 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.

  PMID: 19924591 BACKGROUND

• 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.

  PMID: 12154366 BACKGROUND

MeSH Terms

Conditions

Tobacco Use Disorder; Substance-Related Disorders

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Results Point of Contact

• Title: Prof. Joshua Brown
• Organization: Indiana University

jwmbrown@iu.edu

812 855-9282

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: This will be single-blind masking as the experimenter will need to know which intervention to run on the participant.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Psychological and Brain Sciences

Model Details: One group of 20 participants will receive active TI-NDBS and another group of 20 participants will receive sham TI-NDBS. A third group of 20 participants will receive traditional transcranial direct current stimulation (tDCS).

Study Record Dates

• First Submitted: June 5, 2020
• First Posted: June 16, 2020
• Study Start: July 6, 2020
• Primary Completion: April 21, 2022
• Study Completion: April 21, 2022
• Last Updated: June 24, 2025
• Results First Posted: June 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)