Nicotine Use Disorder, Substance Use Disorders
Conditions
Keywords
Nicotine Addiction, Non-invasive deep brain stimulation, Substance Use Disorders
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.
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
DEVICEActive 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.
OTHERSham TI-NDBS
This is the control condition in which participants will receive sham stimulation for 60 minutes.
DEVICEtDCS
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.
Sponsors
Indiana University School of Medicine
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
This will be single-blind masking as the experimenter will need to know which intervention to run on the participant.
Intervention model description
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* 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.
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Nicotine Craving | 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 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\*\* |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 10 |
| 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. | 0 |
| 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. | 0 |
| 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. | 0 |
| 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. | 0 |
| Total | 10 |
Baseline characteristics
| Characteristic | Phase 3 Sham TI-NDBS | Total | Phase 4 Sham Stimulation | Phase 4 TI-NDBS | Phase 4 Traditional tDCS | Phase 3 Active TI-NDBS |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 10 Participants | 0 Participants | 0 Participants | 0 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | — | 0 Participants | — | — | — | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | — | 10 Participants | — | — | — | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | — | 0 Participants | — | — | — | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | — | 0 Participants | — | — | — | 0 Participants |
| Race (NIH/OMB) Asian | — | 0 Participants | — | — | — | 0 Participants |
| Race (NIH/OMB) Black or African American | — | 0 Participants | — | — | — | 0 Participants |
| Race (NIH/OMB) More than one race | — | 0 Participants | — | — | — | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | — | 0 Participants | — | — | — | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | — | 0 Participants | — | — | — | 0 Participants |
| Race (NIH/OMB) White | — | 10 Participants | — | — | — | 10 Participants |
| Region of Enrollment United States | — | 10 participants | — | — | — | 10 participants |
| Sex: Female, Male Female | — | 6 Participants | — | — | — | 6 Participants |
| Sex: Female, Male Male | — | 4 Participants | — | — | — | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 1 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
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\*\*
Time frame: 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.
Population: Note the results here cannot be interpreted meaningfully as we were unable to run the control group, so there is no valid comparison.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 3 Active TI-NDBS | Change in Nicotine Craving | 4.25 reduction in nicotine craving on 10-pt | Standard Deviation 1.71 |