Opioid-use DisorderNCT05049460
Adjunctive Transcranial Stimulation to Reduce Impulsivity in Opiate Use Disorder
A study testing Theta Burst Stimulation in people with Opioid-use Disorder and Tobacco Use Disorder, run by Gopalkumar Rakesh at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Opioid-use Disorder, Tobacco Use Disorder
- What is being tested?
- Theta Burst Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Sep 2021to 31 Jul 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 9Show fewer
- Stabilized on maintenance buprenorphine if having comorbid opioid use disorder
- Able to read and speak English
- Able to provide informed consent to participate.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Opioid-use Disorder, Tobacco Use Disorder
- Being tested
- Theta Burst Stimulation, Sham TMS
- Medical subject headings
- Opioid-Related Disorders, Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Theta Burst StimulationDevice
Four sessions of theta burst stimulation (TBS) at 120 % RMT and comprising 7200 pulses, given with functional targeting.
Sham TMSDevice
Four sessions of sham TMS, done using the A/P MagVenture coil, with subject's head separated from the coil by foam padding.
| Study group | Role | What they receive |
|---|---|---|
| Active intervention | Active comparator | 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. Receives: Device: Theta Burst Stimulation |
| Sham TMS | Placebo comparator | Four sessions of sham TMS. Targeting will be done using neuronavigation and processed resting state brain scan. Receives: Device: Sham TMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline
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.
Measured: Immediately after intervention (sessions of TBS or sham TMS)
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.
Measured: Baseline
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.
Measured: Immediately after intervention (sessions of TBS or sham TMS)
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.
Measured: Baseline
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.
Measured: Immediately after intervention (sessions of TBS or sham TMS)
Secondary outcomes (1)
Number of Participants Showing Functional Connectivity Changes
Changes in resting state network changes caused by TBS/sham TMS
Measured: Baseline and immediately after intervention (sessions of TBS or sham TMS)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2021
- Study start15 Sep 2021
- Primary completion31 Jul 2024
- Study completion31 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid-use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gopalkumar Rakesh
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Gopalkumar Rakesh, University of Kentucky
- Investigators
- Craig Rush, PhD, Study chair, Professor, Department of Behavioral Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05049460
- Sponsor's protocol ID
- 56570
- Status last verified
- Oct 2025
- First submitted
- 8 Sep 2021
- Last updated
- 22 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Rakesh G, Alcorn JL 3rd, Khanal R, Himelhoch SS, Rush CR. Comparing cigarette-cue attentional bias between people with HIV/AIDS and people with opioid use disorder who smoke. Health Psychol Behav Med. 2023 Sep 7;11(1):2255028. doi: 10.1080/21642850.2023.2255028. eCollection 2023.
PubMed 37693107
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjunctive Transcranial Stimulation to Reduce Impulsivity in Opiate Use Disorder
- ClinicalTrials.gov ID
- NCT05049460
- Acronym / sponsor ID
- 56570
- Conditions
- Opioid-use Disorder, Tobacco Use Disorder
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Gopalkumar RakeshUniversity, hospital or other
- Study start
- 15 Sep 2021 (actual)
- Primary completion
- 31 Jul 2024 (actual)
- Study completion
- 31 Jul 2024 (actual)
- First posted
- 20 Sep 2021 (actual)
- Results
- Posted 22 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active intervention | Active comparator | Device: Theta Burst StimulationFour 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. |
| Sham TMS | Placebo comparator | Device: Sham TMSFour sessions of sham TMS. Targeting will be done using neuronavigation and processed resting state brain scan. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Theta Burst StimulationFour sessions of theta burst stimulation (TBS) at 120 % RMT and comprising 7200 pulses, given with functional targeting. | Device | Active intervention |
| Sham TMSFour sessions of sham TMS, done using the A/P MagVenture coil, with subject's head separated from the coil by foam padding. | Device | Sham TMS |
Primary outcome
Attentional Bias for Smoking Stimuli
Time frame: 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 Smoking Stimuli
Time frame: Immediately after intervention (sessions of TBS or sham TMS)
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.
Attentional Bias for Opioid Stimuli
Time frame: 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.
Attentional Bias for Opioid Stimuli
Time frame: Immediately after intervention (sessions of TBS or sham TMS)
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
Time frame: 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.
Craving
Time frame: Immediately after intervention (sessions of TBS or sham TMS)
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.
1 secondary outcome
Number of Participants Showing Functional Connectivity Changes
Time frame: Baseline and immediately after intervention (sessions of TBS or sham TMS)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37693107Rakesh G, Alcorn JL 3rd, Khanal R, Himelhoch SS, Rush CR. Comparing cigarette-cue attentional bias between people with HIV/AIDS and people with opioid use disorder who smoke. Health Psychol Behav Med. 2023 Sep 7;11(1):2255028. doi: 10.1080/21642850.2023.2255028. eCollection 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Craig Rush, PhD study chair
Professor, Department of Behavioral Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Theta Burst Stimulation in people with Opioid-use Disorder and Tobacco Use Disorder, run by Gopalkumar Rakesh at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Attentional Bias for Smoking Stimuli (time frame: Baseline). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05049460, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2025.