Opioid-use Disorder, Tobacco Use Disorder
Conditions
Brief summary
The goal of this study is to examine the effect of four sessions of theta burst stimulation (TBS) versus sham TMS on attentional bias for smoking and opioid cues versus neutral stimuli in a population of patients with tobacco use disorder (TUD) with comorbid opioid use disorder (OUD) that is stable and on treatment with buprenorphine. The investigators will also examine the effect of TBS on craving for cigarettes as well as opioids. Participants will perform a stress induction procedure that mirrors an optimum combination of cues that trigger tonic craving in their environment while exposed to stress. All four sessions of TBS/sham TMS will be performed on the same day, with each session lasting for approximately 10 minutes and separated by 50 minute intervals.
Detailed description
Tobacco use disorder (TUD) is highly comorbid with opioid use disorder (OUD). Craving in TUD as well as OUD is of two kinds - phasic and tonic. Phasic craving is present at baseline and tonic craving is accentuated by environmental stimuli. A predominant mediator of tonic craving is attentional bias (AB) for environmental stimuli related to either smoking or opioid use. The study is comprised of two days of participation. On the first day, participants will perform two attentional bias (AB) paradigms - one to assess their baseline AB for smoking cues versus neutral cues and another AB paradigm to assess baseline AB for opioid cues versus neutral cues. Craving will be assessed using tobacco craving questionnaire and a visual analogue scale (for opioids), in the context of participants performing a stress induction procedure (which will be a combination of the cold pressor test and PASAT). The investigators will also acquire a baseline resting state fMRI in addition to MRPAGE structural T1 and T2W sequences. On the second day, participants will receive either four sessions of TBS or sham TMS. Targeting will be down using processed resting state brain scan. Each session of TBS or sham TMS will last approximately 10 minutes. During each of the 50 minute intervals between stimulation sessions, participants will perform AB paradigms for smoking and opioids. The craving scale with stress induction will be performed twice - once before the sessions and once after the four sessions of TBS/sham TMS. The investigators will also acquire resting state scans after the four sessions of TBS/sham TMS.
Interventions
DEVICETheta Burst Stimulation
Four sessions of theta burst stimulation (TBS) at 120 % RMT and comprising 7200 pulses, given with functional targeting.
DEVICESham TMS
Four sessions of sham TMS, done using the A/P MagVenture coil, with subject's head separated from the coil by foam padding.
Sponsors
Gopalkumar Rakesh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Patients enrolled in the SMART Clinic at University of Kentucky * 18-60 years of age * Preferably right hand dominant * Currently self-report smoking 10 of more cigarettes per day or a score of \> 5 on the Fagerstrom Test for Nicotine * Willing and able to abstain from all drug use * Exhaled breath on day of study CO \< 10 ppm * Stabilized on maintenance buprenorphine if having comorbid opioid use disorder * Able to read and speak English * Able to provide informed consent to participate.
Exclusion criteria
* Pregnant, nursing, or becoming pregnant during the study. * History of traumatic brain injury or seizures which are contraindications for transcranial magnetic stimulation (TMS). * Increased risk of seizure for any reason, including prior diagnosis of epilepsy, seizure disorder, increased intracranial pressure, or history of significant head trauma with loss of consciousness for ≥ 5 minutes which are all contraindications for TMS. * Presence of intracranial implants (e.g. aneurysms clips, shunts, stimulators, cochlear implants, or electrodes), cardiac pacemakers, or vagus nerve stimulation device which are all contraindications for magnetic resonance imaging. * Neurological disorder including, but not limited to: space occupying brain lesion; any history of seizures, history of cerebrovascular accident; fainting, cerebral aneurysm, major neurocognitive disorder, Huntington chorea; multiple sclerosis which are all contraindications for TMS.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Attentional Bias for Smoking Stimuli | Baseline | Attentional bias was measured at baseline using a visual probe task administered (adapted for smoking images) on a computer and an eye tracker. Images of cigarettes and matched neutral images were presented on a laptop screen, 3 cm apart. Upon offsetting the image pairs, a visual probe (X) appeared on either the left or right side of the screen, in the exact location of one of the previously presented images. Attentional bias is quantified by subtracting the average fixation time on neutral cues from the average fixation time on cigarette cues. The fixation time is measured with an eye tracker in milliseconds. |
| Attentional Bias for Opioid Stimuli | Baseline | Attentional bias was measured using a visual probe task administered (adapted for opioid images) on a computer and an eye tracker. Images of opioids and matched neutral images were presented on a laptop screen, 3 cm apart. Upon offsetting the image pairs, a visual probe (X) appeared on either the left or right side of the screen, in the exact location of one of the previously presented images. Attentional bias is quantified by subtracting the average fixation time on neutral cues from the average fixation time on opioid cues. The fixation time is measured with an eye tracker in milliseconds. |
| Craving | Baseline | The Tobacco Craving Questionnaire-short form (TCQ-SF) consists of 12 items rated on a visual analogue scale from 0 to 84 with a higher score equating to increased craving. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Showing Functional Connectivity Changes | Baseline and immediately after intervention (sessions of TBS or sham TMS) | Changes in resting state network changes caused by TBS/sham TMS |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Intervention Four sessions of theta burst stimulation, amounting to 7200 pulses at 120% resting motor threshold. Targeting will be done using neuronavigation and processed resting state brain scan.
Theta Burst Stimulation: Four sessions of theta burst stimulation (TBS) at 120 % RMT and comprising 7200 pulses, given with functional targeting. | 8 |
| Sham TMS Four sessions of sham TMS. Targeting will be done using neuronavigation and processed resting state brain scan.
Sham TMS: Four sessions of sham TMS, done using the A/P MagVenture coil, with subject's head separated from the coil by foam padding. | 7 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Active Intervention | Sham TMS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 7 Participants | 15 Participants |
| Age, Continuous | 38.13 years STANDARD_DEVIATION 10.97 | 35.43 years STANDARD_DEVIATION 5.16 | 36.87 years STANDARD_DEVIATION 8.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 7 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 8 participants | 7 participants | 15 participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 7 |
| other Total, other adverse events | 0 / 8 | 0 / 7 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 |
Outcome results
Primary
Attentional Bias for Opioid Stimuli
Attentional bias was measured using a visual probe task administered (adapted for opioid images) on a computer and an eye tracker. Images of opioids and matched neutral images were presented on a laptop screen, 3 cm apart. Upon offsetting the image pairs, a visual probe (X) appeared on either the left or right side of the screen, in the exact location of one of the previously presented images. Attentional bias is quantified by subtracting the average fixation time on neutral cues from the average fixation time on opioid cues. The fixation time is measured with an eye tracker in milliseconds.
Time frame: Immediately after intervention (sessions of TBS or sham TMS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Intervention | Attentional Bias for Opioid Stimuli | 305.80 milliseconds | Standard Error 196.95 |
| Sham TMS | Attentional Bias for Opioid Stimuli | 158.61 milliseconds | Standard Error 198.75 |
Primary
Attentional Bias for Opioid Stimuli
Attentional bias was measured using a visual probe task administered (adapted for opioid images) on a computer and an eye tracker. Images of opioids and matched neutral images were presented on a laptop screen, 3 cm apart. Upon offsetting the image pairs, a visual probe (X) appeared on either the left or right side of the screen, in the exact location of one of the previously presented images. Attentional bias is quantified by subtracting the average fixation time on neutral cues from the average fixation time on opioid cues. The fixation time is measured with an eye tracker in milliseconds.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Intervention | Attentional Bias for Opioid Stimuli | 373.09 milliseconds | Standard Error 176.06 |
| Sham TMS | Attentional Bias for Opioid Stimuli | 132.01 milliseconds | Standard Error 70.89 |
Primary
Attentional Bias for Smoking Stimuli
Attentional bias was measured at baseline using a visual probe task administered (adapted for smoking images) on a computer and an eye tracker. Images of cigarettes and matched neutral images were presented on a laptop screen, 3 cm apart. Upon offsetting the image pairs, a visual probe (X) appeared on either the left or right side of the screen, in the exact location of one of the previously presented images. Attentional bias is quantified by subtracting the average fixation time on neutral cues from the average fixation time on cigarette cues. The fixation time is measured with an eye tracker in milliseconds.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Intervention | Attentional Bias for Smoking Stimuli | 501.53 milliseconds | Standard Error 145.24 |
| Sham TMS | Attentional Bias for Smoking Stimuli | 406.70 milliseconds | Standard Error 116.41 |
Primary
Attentional Bias for Smoking Stimuli
Attentional bias was measured using a visual probe task administered (adapted for smoking images) on a computer and an eye tracker. Images of cigarettes and matched neutral images were presented on a laptop screen, 3 cm apart. Upon offsetting the image pairs, a visual probe (X) appeared on either the left or right side of the screen, in the exact location of one of the previously presented images. Attentional bias is quantified by subtracting the average fixation time on neutral cues from the average fixation time on cigarette cues. The fixation time is measured with an eye tracker in milliseconds.
Time frame: Immediately after intervention (sessions of TBS or sham TMS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Intervention | Attentional Bias for Smoking Stimuli | 275.83 milliseconds | Standard Error 158.14 |
| Sham TMS | Attentional Bias for Smoking Stimuli | 414.52 milliseconds | Standard Error 254.3 |
Primary
Craving
The Tobacco Craving Questionnaire-short form (TCQ-SF) consists of 12 items rated on a visual analogue scale from 0 to 84 with a higher score equating to increased craving.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Intervention | Craving | 57.8 units on a scale | Standard Error 5.3 |
| Sham TMS | Craving | 53.1 units on a scale | Standard Error 6.1 |
Primary
Craving
The Tobacco Craving Questionnaire-short form (TCQ-SF) consists of 12 items rated on a visual analogue scale from 0 to 84 with a higher score equating to increased craving.
Time frame: Immediately after intervention (sessions of TBS or sham TMS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Intervention | Craving | 54.1 units on a scale | Standard Error 6.3 |
| Sham TMS | Craving | 48.7 units on a scale | Standard Error 4.9 |
Secondary
Number of Participants Showing Functional Connectivity Changes
Changes in resting state network changes caused by TBS/sham TMS
Time frame: Baseline and immediately after intervention (sessions of TBS or sham TMS)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Intervention | Number of Participants Showing Functional Connectivity Changes | 7 Participants |
| Sham TMS | Number of Participants Showing Functional Connectivity Changes | 7 Participants |