NCT07210268

Brief Summary

This clinical study is testing whether a new non-invasive brain stimulation method, called temporal interference (TI), can reduce nicotine cravings and usage in people who vape. TI delivers mild electrical currents to the scalp in a way that targets deep brain areas involved in addiction, without the need for surgery. In this randomized controlled trial, participants will be assigned to one of three groups: TI stimulation to the nucleus accumbens, TI stimulation to the anterior insula, or a placebo (sham) condition. Each participant will attend a single stimulation session after 8 hours of nicotine abstinence and will use a custom vape device that measures real-time nicotine inhalation. Craving levels will be reported during and after the session. The study aims to determine whether TI to the insula or nucleus accumbens is more effective at decreasing cravings and nicotine inhalation, and whether either is more effective than sham stimulation. For one week after the session, participants will use a smartphone app to track nicotine use and cravings. The primary hypothesis is that TI stimulation to deep brain regions will reduce both nicotine craving and actual use, immediately after stimulation and over the following week, compared to the sham condition.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P50-P75 for not_applicable

Timeline
9mo left

Started Jan 2026

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress26%
Jan 2026Feb 2027

First Submitted

Initial submission to the registry

September 29, 2025

Completed
8 days until next milestone

First Posted

Study publicly available on registry

October 7, 2025

Completed
4 months until next milestone

Study Start

First participant enrolled

January 22, 2026

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 20, 2027

Expected
7 days until next milestone

Study Completion

Last participant's last visit for all outcomes

February 27, 2027

Last Updated

February 10, 2026

Status Verified

February 1, 2026

Enrollment Period

1.1 years

First QC Date

September 29, 2025

Last Update Submit

February 6, 2026

Conditions

Nicotine Use DisorderSubstance Use Disorders

Keywords

Nicotine AddictionNon-invasive deep brain stimulationSubstance Use DisordersTemporal Interference StimulationBOLD Activation

Outcome Measures

Primary Outcomes (2)

  • Change in Nicotine Craving From Baseline to End of Stimulation Session

    Nicotine craving will be assessed using a 1-10 Likert scale (1 = no craving, 10 = extremely strong craving) administered every 10 minutes during the 60-minute temporal interference (TI) stimulation session. The primary outcome is the change in self-reported craving from baseline (pre-stimulation) to the final rating at the 60-minute time point. This measure will assess the immediate effect of TI stimulation targeting either the nucleus accumbens or anterior insula on nicotine craving relative to sham stimulation.

    Baseline to 60 minutes post-stimulation initiation (during the single stimulation session)

  • Change in Nicotine Vapor Inhalation Volume From Baseline to End of 60-Minute Stimulation Session

    Nicotine use will be assessed using a custom vape device that continuously measures the volume of inhaled vapor during the 60-minute stimulation session. The primary outcome is the change in total vapor volume compared to baseline, assessed across all three groups (NAcc, anterior insula, and sham).

    Baseline to 60 minutes post-stimulation initiation

Secondary Outcomes (2)

  • Change in Self-Reported Nicotine Craving Over 7-Day Post-Stimulation Period

    Daily for 7 days post-stimulation

  • Change in Self-Reported Nicotine Use Frequency Over 7-Day Post-Stimulation Period

    Daily for 7 days post-stimulation

Other Outcomes (1)

  • Change in Cognitive Function (Digit Span Test) From Pre- to Post-Stimulation

    Immediately before to 10 minutes after stimulation session

Study Arms (3)

TI Stimulation - Nucleus Accumbens

EXPERIMENTAL

Participants in this arm will receive 60 minutes of temporal interference (TI) stimulation targeted to the nucleus accumbens (NAcc). TI will be delivered using two electrode sets, with placement determined to optimize stimulation of this region. Stimulation will use up to 2 mA per electrode at carrier frequencies of 2000 Hz and 2020 Hz, producing a 20 Hz beat frequency. Craving ratings will be collected every 10 minutes, and nicotine vapor use will be measured in real time.

Device: TI-NDBS

TI Stimulation - Anterior Insula

EXPERIMENTAL

Participants in this arm will receive 60 minutes of temporal interference (TI) stimulation targeted to the anterior insula (AI). TI will be delivered using two electrode sets, with placement determined to optimize stimulation of this region. Stimulation will use up to 2 mA per electrode pair at carrier frequencies of 2000 Hz and 2020 Hz, producing a 20 Hz beat frequency. Craving ratings will be collected every 10 minutes, and nicotine vapor use will be measured in real time.

Device: TI-NDBS

Sham Stimulation

SHAM COMPARATOR

Participants in this arm will receive sham temporal interference (TI) stimulation that mimics the initial sensation of active stimulation. The current will ramp up over 30 seconds and immediately ramp back down, with no sustained current. This procedure controls for sensory experience and participant expectations. Electrode placement will mirror that used in the active conditions. Participants will complete the same craving assessments and use the same custom vape device as in the experimental arms.

Device: Sham TI-NDBS

Interventions

TI-NDBSDEVICE

In the active TI-NDBS condition, participants receive transcranial stimulation for 60 minutes through scalp electrodes using temporal interference (TI). Two electrode sets deliver high-frequency alternating currents (e.g., 2000 Hz and 2020 Hz), generating a 20 Hz beat frequency at depth to stimulate targeted brain regions. Stimulation is delivered in six 10-minute blocks with 30-second ramp-up and ramp-down periods to minimize discomfort. Electrode configurations differ by group to target either the nucleus accumbens or anterior insula, based on finite element modeling. The maximum current is up to 2 mA per electrode, and no single region receives more than 2 mA.

Also known as: Temporal Interference Non-invasive Deep Brain Stimulation
TI Stimulation - Anterior InsulaTI Stimulation - Nucleus Accumbens
Sham TI-NDBSDEVICE

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

Sham Stimulation

Eligibility Criteria

Age21 Years - 50 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Between the ages of 21 and 50
  • Nicotine dependent and vape at least 15 mg nicotine per day
  • Must have a phone with internet access
  • Participants must have at least a 6th grade education and be able to speak and read English

You may not qualify if:

  • History of seizures, seizure disorders, or familial history of seizure disorders
  • History of intractable migraine or complicated migraine syndromes
  • History of suicide attempts or active suicidal ideation (past month)
  • History of cardiac arrhythmias, prolonged QT, pacemakers, or cardiovascular disorders
  • Hypertension with systolic BP \>150mmHgCentral nervous system structural lesions (tumors, MS, strokes, etc.)
  • Active neuropsychiatric disorders (schizophrenia, bipolar, active psychosis, dementia, etc.)
  • History of head trauma with loss of consciousness, skull fractures, subdural hematomas
  • Active opioid, cocaine, and/or methamphetamine use
  • Active severe cannabis use disorder
  • Active alcohol use disorder or history of alcohol withdrawal
  • Metal implants in the head or under the scalp (excluding dental implants)
  • Current smoking cessation treatment or medications affecting reward processing
  • Pregnancy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Indiana University

Bloomington, Indiana, 47403, United States

RECRUITING

Related Publications (6)

  • Modak P, Fine J, Colon B, Need E, Cheng H, Hulvershorn L, Finn P, Brown JW. Temporal interference electrical neurostimulation at 20 Hz beat frequency leads to increased fMRI BOLD activation in orbitofrontal cortex in humans. Brain Stimul. 2024 Jul-Aug;17(4):867-875. doi: 10.1016/j.brs.2024.07.014. Epub 2024 Jul 24.

    PMID: 39059712BACKGROUND

  • 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: 28575667BACKGROUND

  • Violante IR, Alania K, Cassara AM, Neufeld E, Acerbo E, Carron R, Williamson A, Kurtin DL, Rhodes E, Hampshire A, Kuster N, Boyden ES, Pascual-Leone A, Grossman N. Publisher Correction: Non-invasive temporal interference electrical stimulation of the human hippocampus. Nat Neurosci. 2023 Dec;26(12):2252. doi: 10.1038/s41593-023-01517-y. No abstract available.

    PMID: 37957321BACKGROUND

  • 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: 17255515BACKGROUND

  • Wessel MJ, Beanato E, Popa T, Windel F, Vassiliadis P, Menoud P, Beliaeva V, Violante IR, Abderrahmane H, Dzialecka P, Park CH, Maceira-Elvira P, Morishita T, Cassara AM, Steiner M, Grossman N, Neufeld E, Hummel FC. Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning. Nat Neurosci. 2023 Nov;26(11):2005-2016. doi: 10.1038/s41593-023-01457-7. Epub 2023 Oct 19.

    PMID: 37857774BACKGROUND

  • Joutsa J, Moussawi K, Siddiqi SH, Abdolahi A, Drew W, Cohen AL, Ross TJ, Deshpande HU, Wang HZ, Bruss J, Stein EA, Volkow ND, Grafman JH, van Wijngaarden E, Boes AD, Fox MD. Brain lesions disrupting addiction map to a common human brain circuit. Nat Med. 2022 Jun;28(6):1249-1255. doi: 10.1038/s41591-022-01834-y. Epub 2022 Jun 13.

    PMID: 35697842BACKGROUND

Related Links

MeSH Terms

Conditions

Tobacco Use DisorderSubstance-Related Disorders

Condition Hierarchy (Ancestors)

Chemically-Induced DisordersMental Disorders

Study Officials

  • Joshua Brown

    Indiana University, Bloomington

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Joshua Brown, PhD

CONTACT

812-855-9282jwmbrown@iu.edu

Kendall Moore, BS

CONTACT

(812) 856-1846kem12@iu.edu

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Masking Details
Participants will receive either active or sham stimulation with ramping protocols designed to mimic sensory experience across conditions. Participants are blinded to condition, and self-reported outcomes are collected through blinded survey methods.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Participants will be randomly assigned to one of three groups: temporal interference stimulation to the nucleus accumbens, temporal interference stimulation to the anterior insula, or sham stimulation.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

September 29, 2025

First Posted

October 7, 2025

Study Start

January 22, 2026

Primary Completion (Estimated)

February 20, 2027

Study Completion (Estimated)

February 27, 2027

Last Updated

February 10, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will not share

Locations

US(1)