Opioid Use Disorder, Tobacco Use Disorder
Conditions
Keywords
Deep Transcranial Magnetic Stimulation, Transcranial Magnetic Stimulation, Smoking Cessation, Cigarette Smoking, Neuromodulation, H4 Coil, Insular Cortex, Prefrontal Cortex, Tobacco Craving, Opioid Craving, Tobacco Cue Reactivity, Medications for Opioid Use Disorder, Buprenorphine, Methadone
Brief summary
This pilot study will evaluate the use of deep transcranial magnetic stimulation (Deep TMS) to help adults with opioid use disorder (OUD) who are receiving medications for opioid use disorder (MOUD) such as buprenorphine or methadone and who continue to smoke cigarettes and want to quit. Deep TMS is a noninvasive form of brain stimulation that uses magnetic pulses. The BrainsWay Deep TMS System is cleared by the U.S. Food and Drug Administration (FDA) for smoking cessation. This study will use the H4 coil smoking-cessation protocol in people with OUD receiving MOUD. Approximately 12 participants will take part and all participants will receive active Deep TMS. There is no sham or placebo group and no random assignment. Participants may receive up to 18 Deep TMS sessions over 6 weeks: five sessions per week during the first 3 weeks, followed by one session per week during Weeks 4 through 6. Participants will return for a follow-up visit at Week 10. The main purpose of the study is to learn whether this Deep TMS approach is safe, tolerable and feasible for people with OUD receiving MOUD and to estimate how many participants are able to remain smoke-free from Week 6 through Week 10. The study will also look for early changes in tobacco craving, opioid craving, continuation of MOUD, mood and anxiety symptoms, pain, heart rate variability, and participants' experiences with the treatment. The findings will be used to help plan a larger future study.
Interventions
DEVICEDeep TMS System With H4 Coil
Active Deep TMS will be delivered using the Deep TMS System with the H4 coil according to the smoking-cessation protocol. Stimulation will be delivered at 120% of the participant's resting motor threshold, unless a protocol-approved modification is required, at 10 hertz (Hz) using 3-second trains, a 15-second inter-train interval, 60 trains, and 1,800 pulses per session. Each stimulation session lasts approximately 20 minutes. Participants may receive five sessions per week during Weeks 1 through 3, followed by one session per week during Weeks 4 through 6, for up to 18 sessions total.
Sponsors
Payel Roy
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
22 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male or female participants, 22-70 years old. * Chronic, heavy smoker (\>10 cigarettes/day for \>1 year) with no continuous abstinence period \>3 months in the past 12 months (self-report), and baseline smoking confirmed by either (a) cotinine-positive urine or (b) clinical documentation of current smoking when cotinine interpretation is not reliable due to nicotine replacement or other nicotine product use reported at baseline. * Motivated to quit smoking, defined as a Motivation To Stop Scale (MTSS) score ≥6 at baseline (i.e., endorsing intention to quit within the next 3 months or within the next month). * Meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for moderate or severe Opioid Use Disorder (OUD), with diagnosis confirmed by the study investigator through clinical interview study assessment. * Meet DSM-5 diagnostic criteria for Severe Tobacco Use Disorder, confirmed by the study investigator through clinical interview study assessment. * Have received buprenorphine or methadone consistently for the last 3 months (≥80% proportion of days covered or equivalent documentation for clinic-administered dosing, such as opioid treatment program dosing records or medication administration records demonstrating consistent dosing over the same 3-month period). * No self-reported illicit fentanyl use in the past 30 days AND evidence of fentanyl-negative urine toxicology, defined as either (a) a documented fentanyl-negative urine drug screen in the medical record within 7 days prior to consent or (b) a fentanyl-negative urine toxicology obtained at baseline screening. * Able to communicate fluently in English for accurate administration of assessments and safety monitoring. * For participants with the potential to become pregnant: pregnancy status must be confirmed after informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization and before study treatment. Participants must have either (a) a negative urine pregnancy test obtained by the study team at baseline after informed consent or (b) a documented negative serum or urine human chorionic gonadotropin (hCG) result from standard clinical care within 7 days prior to consent, reviewed or abstracted by the study team only after informed consent and HIPAA authorization. * At least one prior quit attempt in the past 12 months, defined as intentionally stopping smoking for ≥24 hours (≥1 day) because they were trying to quit, assessed by self-report at baseline screening.
Exclusion criteria
* History of seizure disorder, epilepsy, stroke, significant head trauma, or other clinically significant neurologic condition or structural brain lesion (e.g., tumor, vascular malformation, intracranial aneurysm/aneurysm repair, meningitis/encephalitis with neurologic sequelae). * Metallic, electronic, magnetically activated, or retained metal implants/devices that may contraindicate Deep TMS exposure, including but not limited to pacemaker/implantable cardioverter-defibrillator, cochlear or otologic implants, implanted hearing-aid anchors, deep brain stimulator, vagus nerve stimulator, aneurysm clip/coil, carotid/cerebral stent, ocular metallic implant/stent, cerebrospinal fluid shunt, intracardiac lines/wires, implanted pump, retained bullet/pellet/shrapnel, staples/sutures or metal hardware in or around the head/neck, skull/cervical fixation plates, titanium skull plates, magnetically activated dental implants, or facial tattoos/permanent makeup with metallic ink, as determined by the investigator. * Unstable or severe medical condition (e.g., uncontrolled cardiac, hepatic, renal, or metabolic disease) that increases risk from study participation, based on medical history review, medical record review, and investigator clinical judgment. * Current pregnancy, intention to become pregnant during the study period, or actively breastfeeding. For participants with the potential to become pregnant, a negative pregnancy test is required before initiating study treatment. * Active psychotic disorder, bipolar mania, or major depressive episode with psychotic features, as determined by the study investigator. * Severe cognitive impairment or neurocognitive disorder that limits the ability to provide informed consent or complete study procedures. Participants unable to complete consent teach-back will be excluded. * Acute intoxication or clinically significant opioid withdrawal at baseline screening, defined as a Clinical Opiate Withdrawal Scale (COWS) score ≥12. * Current or recent (within the past 30 days) use of any medication known to significantly lower the seizure threshold, including but not limited to bupropion, clozapine, olanzapine, clomipramine, amitriptyline, or tramadol, or other clinically significant use determined by the investigator to further lower seizure threshold. * Any lifetime history of electroconvulsive therapy (ECT) or repetitive transcranial magnetic stimulation (rTMS). * Frequent or severe migraine headaches, defined as ≥8 migraine days per month over the past 30 days, or migraine headaches that, in the investigator's clinical judgment, are expected to interfere with tolerating Deep TMS sessions. * Significant hearing loss that, in the investigator's judgment, would prevent safe participation despite use of hearing protection. * Participation in another interventional clinical trial within the last 30 days prior to informed consent. * First-degree family history of epilepsy or seizure disorder (biological parent, full sibling, or child). * History of recurrent syncope or unexplained fainting, including any episode with loss of consciousness or convulsive features, that has not been adequately evaluated/cleared or would increase risk with Deep TMS in the investigator's judgment. * Current prescribed benzodiazepine or anticonvulsant regimen that has not been stable for at least 4 weeks before consent, defined as any new start, discontinuation, dose increase or decrease, route/formulation change, change in scheduled dosing frequency, or, for as-needed medications, a change in prescribed instructions or clinically meaningful increase in frequency or amount used during the 4 weeks before consent, as determined by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Four-Week Continuous Smoking Abstinence (Continuous Quit Rate) | Weeks 6 through 10 (4-week abstinence window), with outcome determination at Week 10 | Continuous smoking abstinence is defined as no cigarettes smoked during the prespecified Weeks 6 through 10 abstinence window based on the daily smoking diary, with abstinence verified by urine cotinine at the Week 10 follow-up visit. Each participant will be classified as meeting or not meeting the continuous quit criteria, and the outcome will be summarized as the percentage of participants meeting the criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Opioid Craving Scale-3 (OCS-3) Total Score | Baseline (Week 0); acute treatment phase (Weeks 1-3), with pre- and post-session scores summarized separately; maintenance phase (Weeks 4-6), with pre- and post-session scores summarized separately; Week 10 follow-up. | Opioid craving will be measured using the 3-item Opioid Craving Scale-3 (OCS-3). Each item is rated from 0 to 10, and the three items are summed to produce a total score ranging from 0 to 30. Higher total scores indicate greater opioid craving or urge to use opioids. OCS-3 will be collected at baseline, before and after each active Deep TMS session during Weeks 1 through 6, and at Week 10. For reporting, each participant's pre-session scores and post-session scores will be averaged separately within the acute treatment phase (Weeks 1 through 3) and maintenance treatment phase (Weeks 4 through 6). These participant-level phase means will then be summarized across participants. Baseline and Week 10 scores will be summarized separately. |
| Percentage of Participants Maintaining Continuous Medication for Opioid Use Disorder (MOUD) Without a Gap Greater Than 14 Days | Baseline through Week 3; Baseline through Week 6; Baseline through Week 10 | MOUD continuity is defined for each analysis window as no gap greater than 14 consecutive days without verified MOUD coverage. Each participant will be classified as maintaining or not maintaining continuous MOUD during each window. The outcome will be summarized as the percentage of participants maintaining continuous MOUD for each analysis window. |
| Medication for Opioid Use Disorder (MOUD) Coverage Measured by Percent Days Covered (PDC) | Baseline through Week 3; Baseline through Week 6; Baseline through Week 10. | MOUD coverage will be measured as Percent Days Covered (PDC) for each analysis window. PDC is calculated as the number of days with verified MOUD coverage divided by the total number of days in the analysis window, multiplied by 100. PDC ranges from 0% to 100%, with higher percentages indicating greater consistency of MOUD availability or receipt. PDC will be summarized continuously for each analysis window. |
| Mean Percentage of Planned Deep TMS Sessions Attended per Participant | From the first Deep TMS session (Week 1) through the end of treatment (Week 6) | For each participant, the session completion rate will be calculated as the number of planned Deep TMS sessions attended divided by the number of planned Deep TMS sessions, multiplied by 100. Participants may receive up to 18 planned sessions: 15 acute-treatment sessions during Weeks 1 through 3 and 3 maintenance sessions during Weeks 4 through 6. The outcome will be summarized across participants as the mean percentage with standard deviation. Higher percentages indicate greater treatment-session completion. |
| Percentage of Attended Deep TMS Sessions Meeting All Protocol Delivery Fidelity Criteria | From the first active Deep TMS session through the end of treatment (Week 6) | Treatment delivery fidelity will be calculated as the number of attended active Deep TMS sessions that meet all applicable protocol delivery criteria divided by the total number of attended active Deep TMS sessions, multiplied by 100. Fidelity criteria include completion of required safety and setup checks, appropriate H4 helmet/coil positioning, device readiness with no unresolved faults, documentation of the resting motor threshold source, stimulation intensity of 120% of resting motor threshold unless a protocol-approved modification is documented, delivery at 10 Hz with 3-second trains, 15-second inter-train intervals, 60 trains and 1,800 pulses, adherence to the protocol schedule window, and documentation of session completion or any interruption or issue. Higher percentages indicate greater adherence to the Deep TMS delivery protocol. |
| Percentage of Participants Experiencing at Least One Deep TMS Device or Delivery Technical Issue | From the first Deep TMS session (Week 1) through the end of treatment (Week 6) | A participant will be counted as having a technical issue if at least one predefined Deep TMS device or delivery problem is documented during the treatment period. Examples include a console error, cooling fault, positioning-arm or helmet/coil fit issue, failed stimulation test, software or diagnostic alert, or an interruption or alarm during stimulation. The outcome will be summarized as the percentage of participants experiencing at least one such issue. Lower percentages indicate fewer technical or delivery problems. |
| Percentage of Approached Individuals Who Consent to Participate (Consent Conversion Rate) | From first participant screening through the end of accrual, approximately 12 months. | Consent conversion rate will be calculated as the number of individuals who provide informed consent divided by the number of individuals successfully approached or invited to participate in the study, multiplied by 100. Individuals who are not successfully approached will not be included in the denominator. Higher percentages indicate greater recruitment reach into the target population. |
| Percentage of Participants Experiencing at Least One Active Deep TMS Session-Related Adverse Effect | From the first active Deep TMS session (Week 1) through the end of treatment (Week 6) | Participants will be counted as having a treatment-related adverse effect if they experience at least one adverse effect associated with an active Deep TMS study session during the treatment period, as assessed and documented by the study team. Adverse effects may include headache, scalp discomfort, facial or jaw twitching, dizziness, tinnitus, or mood changes. The outcome will be summarized as the percentage of participants experiencing at least one active Deep TMS session-related adverse effect. |
Countries
United States
Contacts
CONTACTPayel J Roy, MD, MSc
CONTACTGagandeep Singh Shergill, B Pharm, MS
PRINCIPAL_INVESTIGATORPayel J Roy, MD, MSc
University of Pittsburgh
Outcome results
None listed