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Covid pandemic restrictions delayed data collection and led to loss of funding.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Phase 4 Traditional tDCS | Active Comparator | Participants assigned to this condition will receive traditional transcranial direct current stimulation for 60 minutes for 5 days. |
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| 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. |
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| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Indiana University | Bloomington | Indiana | 47403 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18312035 | Background | 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. | |
| 28575667 | Background |
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We will share anonymized participant data upon request. Beyond that, we will report anonymized data publicly in aggregate.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. 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. |
| FG001 | 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. Sham TI-NDBS: This is the control condition in which participants will receive sham stimulation for 60 minutes. |
| FG002 | Phase 4 Traditional tDCS | Participants assigned to this condition will receive traditional transcranial direct current stimulation for 60 minutes for 5 days. 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. |
| FG003 | 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. 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. |
| FG004 | 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. Sham TI-NDBS: This is the control condition in which participants will receive sham stimulation for 60 minutes. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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COVID delays and lack of funding
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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** | Note the results here cannot be interpreted meaningfully as we were unable to run the control group, so there is no valid comparison. | Posted | Mean | Standard Deviation | reduction in nicotine craving on 10-pt | 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. |
The total duration of collecting information about adverse events across subjects was 1 year, 5 months. Each individual subject was monitored for adverse events over a one day period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Unpleasant sensation | Skin and subcutaneous tissue disorders | Non-systematic Assessment | Subject experienced unpleasant sensation on the scalp which required terminating the session. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Joshua Brown | Indiana University | 812 855-9282 | jwmbrown@iu.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 21, 2023 | May 8, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D014029 | Tobacco Use Disorder |
| D019966 | Substance-Related Disorders |
| ID | Term |
|---|---|
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D065908 | Transcranial Direct Current Stimulation |
| ID | Term |
|---|---|
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
| D003295 | Convulsive Therapy |
| D013000 | Psychiatric Somatic Therapies |
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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).
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This will be single-blind masking as the experimenter will need to know which intervention to run on the participant.
|
|
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| Sham TI-NDBS | Other | This is the control condition in which participants will receive sham stimulation for 60 minutes. |
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| 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. |
|
| 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. |
| 24814566 | 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. |
| 26071624 | 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. |
| 22809824 | 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. |
| 25503588 | 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. |
| 17255515 | 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. |
| 24690001 | 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. |
| 19924591 | 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. |
| 12154366 | 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. |
| BG001 | 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. Sham TI-NDBS: This is the control condition in which participants will receive sham stimulation for 60 minutes. |
| BG002 | Phase 4 Traditional tDCS | Participants assigned to this condition will receive traditional transcranial direct current stimulation for 60 minutes for 5 days. 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. |
| BG003 | 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. 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. |
| BG004 | 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. Sham TI-NDBS: This is the control condition in which participants will receive sham stimulation for 60 minutes. |
| BG005 | Total | Total of all reporting groups |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| 0 |
| 10 |
| 0 |
| 10 |
| 1 |
| 10 |
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| D004191 | Behavioral Disciplines and Activities |
| D004597 | Electroshock |
| D011580 | Psychological Techniques |