---
title: "VICTORY trial protocol: Weekly iTBS to left DLPFC for craving reduction in buprenorphine-treated O"
id: "plos-one-21-vanderbilt-integrated-community-tms-for-opioid-recovery-victory-study-protocol"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-21-vanderbilt-integrated-community-tms-for-opioid-recovery-victory-study-protocol"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357402"
published_at: "2026-09-10T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# VICTORY trial protocol: Weekly iTBS to left DLPFC for craving reduction in buprenorphine-treated O
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-21-vanderbilt-integrated-community-tms-for-opioid-recovery-victory-study-protocol
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357402)
- **Published At:** 2026-09-10T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The VICTORY study is a randomized, single-blind, sham-controlled protocol testing left dorsolateral prefrontal cortex (DLPFC)–targeted intermittent theta burst stimulation (**iTBS**) in people with opioid use disorder (OUD) who are receiving **buprenorphine**. - Up to 120 participants will be enrolled and randomized to active or sham iTBS delivered weekly (two 1800-pulse sessions once per week) for 8 weeks (16 sessions total). - Primary outcomes include changes in **craving**, opioid use, and treatment retention, assessed at baseline and follow-up visits (10, 12, and 20 weeks). - A subset of participants may undergo optional pre- and post-treatment neuroimaging to evaluate neural mechanisms. - The trial will be conducted at an academic medical center and a private outpatient TMS clinic to assess feasibility and generalizability in routine-care settings. - A secondary aim examines whether iTBS-related reductions in craving correlate with changes in functional connectivity between the **left DLPFC** and the **dorsal striatum** and **anterior cingulate cortex (ACC)**. - The protocol responds to gaps in the TMS and OUD literature: prior studies are few, often small, frequently excluded people on buprenorphine, and used varied stimulation schedules (single or accelerated sessions versus repeated-session clinical protocols). - Trial registration is listed on ClinicalTrials.Gov (ID NCT07457489). Funding is from the Tennessee Opioid Abatement Council and NIDA K23DA059690; some investigators are affiliated with a commercial TMS organization, disclosed as competing interests. - The design emphasizes alignment with real-world care (weekly visits) and aims to both test efficacy and clarify neural circuit changes associated with TMS in OUD.
## Clinical Analysis & Structured Key Points
Vanderbilt Integrated Community TMS for Opioid Recovery (VICTORY): Study protocol for a randomized, controlled trial of non-invasive brain stimulation to reduce craving in people with opioid use disorder | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Peer Review Reader Comments Figures Figures Abstract Background Individuals receiving buprenorphine treatment for opioid use disorder (OUD) remain at high risk for treatment discontinuation and return to opioid use. Transcranial magnetic stimulation (TMS) has shown efficacy in reducing craving and substance use in other substance use disorders, but its application in OUD remains limited and the neural mechanism underlying its therapeutic effects is poorly understood. Determining the feasibility and generalizability of TMS in patients receiving buprenorphine – the most commonly prescribed medication for OUD – is therefore critical. This protocol aims to address these issues in a clinical trial of weekly TMS sessions for OUD. Methods We will enroll up to 120 individuals with OUD taking buprenorphine in a randomized, single-blind, sham-controlled trial of left dorsolateral prefrontal cortex (DLPFC)-targeted intermittent theta burst stimulation (iTBS). Participants will receive active or sham iTBS weekly (2 sessions of 1800 pulses each applied once per week x 8 weeks, 16 sessions total) with pre- and post-iTBS assessments (10, 12, 20 weeks) of craving, opioid use, and treatment retention. A subset of individuals will undergo optional pre- and post-iTBS neuroimaging. The study will be conducted at an academic medical center and a private outpatient TMS clinic. Aims Our primary aim is to determine whether 16 sessions of active iTBS applied to the left DLPFC results in reduced craving and opioid use, and higher treatment retention, relative to sham. In a secondary aim, we will also examine whether iTBS-related changes in craving are associated with changes in functional connectivity between the left DLPFC and both the dorsal striatum and anterior cingulate cortex. Discussion By evaluating the feasibility and efficacy of a weekly TMS protocol that aligns with routine care and focuses on patients maintained on buprenorphine, this study addresses key limitations of prior TMS research in OUD. Furthermore, the inclusion of neuroimaging will help characterize the neural mechanisms underlying TMS-related changes in craving. Trial registration This clinical trial is registered at ClinicalTrials.Gov; ID NCT07457489 ; date of registration: 03/02/2026. Citation: Biernacki K, Connolly J, Tunison L, Kast KA, Vandekar S, King B, et al. (2026) Vanderbilt Integrated Community TMS for Opioid Recovery (VICTORY): Study protocol for a randomized, controlled trial of non-invasive brain stimulation to reduce craving in people with opioid use disorder. PLoS One 21(9): e0357402. https://doi.org/10.1371/journal.pone.0357402 Editor: Annesha Sil, PLOS: Public Library of Science, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND Received: August 7, 2026; Accepted: August 18, 2026; Published: September 10, 2026 Copyright: © 2026 Biernacki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: No datasets were generated or analysed during the current study. Funding: This study is supported by a grant from the Tennessee Opioid Abatement Council to H.B.W. This trial sponsor has no authority over design, conduct, analysis or reporting of the trial. This work was also supported by National Institute on Drug Abuse K23DA059690 to H.B.W. Competing interests: MC, JB, and SS are employed by a commercial organization (Synaptic Psych). The study design and report was developed independently of any commercial influence. The remaining authors declare no competing interests and no authors received funding in the form of salary. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Introduction Opioid use disorder (OUD) affects over 16 million people each year and remains the leading cause of fatal overdoses worldwide [ 1 ]. Gold-standard medications for the treatment of OUD, such as buprenorphine, the most widely prescribed medication for OUD [ 2 ], safely reduce mortality and drug use [ 3 , 4 ]. However, even with buprenorphine treatment, relapse and treatment discontinuation rates remain high for people with OUD; the three-month period after treatment initiation presents the highest risk for return to use [ 5 , 6 ]. Within 6 months of starting buprenorphine, only 50% of patients will continue treatment, and 91% will return to use [ 7 ]. Together, these data highlight the need for adjunctive treatments that address the drivers of return to use and treatment discontinuation. Noninvasive brain stimulation has been explored as a treatment for substance use disorders (SUDs), including OUD. Transcranial magnetic stimulation (TMS) is one form of noninvasive brain stimulation that uses electromagnetic pulses to modulate cortical excitability and induce neuroplastic changes [ 8 , 9 ]. The U.S. Food and Drug Administration (FDA) has cleared TMS for the treatment of depression, obsessive-compulsive disorder and for smoking cessation [ 10 ] with clinical protocols typically administering stimulation over the dorsolateral prefrontal cortex (DLPFC) [ 11 ]. Within these applications, intermittent theta burst stimulation (iTBS), a specific type of patterned TMS, has demonstrated significant clinical utility. iTBS is thought to increase synaptic long-term potentiation by enhancing cortical excitability [ 12 , 13 ]. Crucially, reviews and meta-analyses across multiple SUDs have shown that TMS (including iTBS) is effective at reducing craving and substance use [ 14 – 16 ]. It is hypothesized that TMS exerts therapeutic effects by targeting the neural circuits that contribute to drug craving and seeking [ 17 ]. Despite these promising findings, research examining TMS in OUD remains limited, with reviews of noninvasive brain stimulation in OUD identifying only a handful of studies [ 18 – 20 ]. Existing studies of TMS for OUD primarily focus on individuals using heroin and only one study has assessed the impact of accelerated deep TMS in people receiving buprenorphine for OUD [ 21 ]. To date, only four studies have investigated TMS for OUD in North America – where the use of the highly potent synthetic opioid, fentanyl, has been steadily increasing and presents a higher risk of overdose than heroin [ 22 ]. Two of these studies have used single-session TMS protocols to modulate craving or cognition [ 23 , 24 ]. One recently published study evaluated an accelerated TMS protocol in which 4 sessions of iTBS were delivered in a single day to a small sample of patients with OUD who were stable on their maintenance medications [ 25 ]. The authors reported reduced attentional bias to opioid cues, however this did not reach statistical significance. The third study implemented a repeated-sessions clinical protocol with TMS administered daily over multiple weeks [ 26 ]. However, of 87 individuals screened for participation, only 6 were randomized, and 4 completed the study. Accordingly, no statistical analyses were conducted on this small sample, thus limiting the evaluation of clinical efficacy and treatment outcomes. Notably, none of these studies evaluated individuals taking buprenorphine, despite it being the most commonly prescribed medication for OUD in North America [ 2 ]. As such, the following questions remain about the use of TMS for OUD: Is TMS for OUD effective, and if so, how does it exert its effects? Only one study of TMS for OUD has included neuroimaging [ 24 ], despite neuroimaging being critical for helping to characterize the neural circuit changes that occur with TMS treatment. Is a weekly dosing schedule of TMS for OUD a feasible and acceptable adjunctive treatment? A previous study [ 26 ] testing therapeutic TMS protocols (i.e., daily sessions of treatment over multiple weeks) struggled with recruitment and retention, questioning the feasibility and acceptability of this intervention for this population. Can we provide TMS for populations with OUD beyond urban academic medical centers? Expanding access to TMS has been a challenge for the field more broadly, besides the treatment of SUDs. While clinical trials for TMS are typically conducted in academic medical centers, more widespread clinical application would ultimately require delivery of TMS for SUDs in private outpatient clinics nationwide. To address these questions, we designed a multi-site randomized controlled trial of TMS for OUD among individuals receiving buprenorphine treatment. We will implement a novel weekly stimulation protocol designed to improve treatment efficiency and better align TMS delivery with routine weekly clinic visits. The trial will be conducted across both an academic medical center and private practice clinics throughout Tennessee to help address the question of clinical applicability beyond academic medical settings. Our central hypothesis is that DLPFC-targeted iTBS will significantly reduce both opioid craving and opioid use. In secondary analyses, we will use neuroimaging (MRI) to assess whether a change in functional connectivity between the DLPFC and both the dorsal striatum and anterior cingulate cortex (ACC) is associated with reductions in craving. Ultimately, this work aims to establish a safe and effective adjunctive therapy to directly mitigate the severe craving and high relapse rates that limit current OUD treatments. Methods Study design The study is a randomized, single-blind, sham controlled clinical trial of iTBS to reduce opioid craving in people diagnosed with OUD who are currently receiving treatment with buprenorphine. The study consists of 12 study visits. Participants will also have the option to elect to participate in optional MRI scans before and after the intervention. At the first visit (Consent), participants will complete informed consent, which will be obtained by the researcher conducting the study. After completing consent, participants will undergo additional screening procedures to ensure safety to receive TMS (and safety to receive MRI if the participant elects to complete these scans) and will complete questionnaires (listed in Fig 1 ) about substance use and psychiatric symptoms. Enrolled participants will then undergo 8 weekly sessions of left DLPFC-targeted iTBS. Prior to the first TMS visit, individuals will be randomized to receive active or sham iTBS. At each TMS visit, participants will complete questionnaires about their substance use and psychiatric symptoms and provide a sample for urine toxicology. After the 8-week TMS intervention, participants will return for follow-up visits at weeks 10, 12, and 20. At each follow-up visit, participants will complete questionnaires about their substance use and psychiatric symptoms and provide a sample for urine toxicology. If a participant elects to undergo the optional MRI visits, they will undergo 2 MRI scans 1) before the first TMS visit; and 2) after the week 8 TMS visit. During both MRI scans, participants will complete a resting state fMRI and perform a task assessing cue reactivity in the scanner. At these sessions, participants will also complete tasks outside the scanner assessing inhibitory control and reward processing. See Figs 2 and 3 for a visualization of the study design and Fig 1 for a list of assessments conducted on each study visit. This protocol was developed with input from multiple certified peer recovery specialists (T.A., C.G., K.Y.), who are coauthors on this manuscript and have lived experience with substance use. Download: PNG larger image TIFF original image Fig 1. Participant timeline: Schedule of enrollment, interventions, and assessments. *If participant elects to undergo MRI. **If a participant reports a history of bipolar disorder or screens positive on the DSM Screener. ***If able to become pregnant. BAM: Brief Addiction Monitor; BDI: Beck Depression Inventory; BPI: Brief Pain Inventory; MRI: Magnetic Resonance Imaging; OCS: Opioid Craving Scale; PCL5: PTSD Checklist for DSM-5; SCID: Structured Clinical Interview for DSM-5; SOWS: Subjective Opiate Withdrawal Scale; STAI: State-Trait Anxiety Inventory; TMS: Transcranial Magnetic Stimulation; TLFB: Timeline Follow Back; TRQ: Time to Relapse Questionnaire. https://doi.org/10.1371/journal.pone.0357402.g001 Download: PNG larger image TIFF original image Fig 2. Study Protocol Diagram. After consent and randomization to receive active or sham stimulation, participants will receive iTBS weekly (2 sessions once per week x 8 weeks) with pre- and post-intervention assessments of craving, opioid use, and treatment retention. RMT: resting motor threshold. https://doi.org/10.1371/journal.pone.0357402.g002 Download: PNG larger image TIFF original image Fig 3. Diagram of schedule of assessments. Participants will complete assessments of opioid use, treatment engagement and retention, drug use, craving and other psychiatric assessments before and after receiving TMS treatment. A subset of participants will also complete an optional neuroimaging session at baseline and post-TMS where measures of craving and cognition will be collected. https://doi.org/10.1371/journal.pone.0357402.g003 Study approval and registration This protocol is approved by the Vanderbilt University Medical Center (VUMC) Institutional Review Board (IRB) and Advarra IRB (VUMC Protocol ID: 251293; Advarra Protocol ID: Pro00094328). Modifications to the protocol (at both sites) will be communicated to the study teams by electronic notification (e.g., email). The protocol has also been registered at ClinicalTrials.gov (ID: NCT07457489). Results from this trial will be reported in ClinicalTrials.gov and will be published in academic journals. Results may also be disseminated at academic and medical conferences. Study setting The study will include two enrolling sites, one of which is a medical academic institution (VUMC) and the other a private psychiatric clinic (SynapticPSYCH). Both sites have experience conducting research using TMS methods. Research ethics approval for the academic institution is covered by an institutional IRB. Research ethics approval for the clinic site is covered by an external central IRB. Protocol amendments will be submitted to the institutional IRB and external central IRB, which will send electronic notifications or changes required directly to the participating sites. Inclusion and exclusion criteria Inclusion criteria Age between 18–65 years Diagnosis of OUD according to DSM-5 criteria and confirmed by SCID [ 27 ] Currently prescribed buprenorphine for opioid use disorder Meets either of the following criteria: (1) reports opioid craving of 2 or greater on a 0–10 scale, or (2) has returned to opioid use at least once within the past 12 months Must be able to read, speak and understand English Must be judged by study staff to be capable of completing the study procedures Participants will be in stable outpatient psychiatric treatment and psychiatrically stable. Exclusion criteria DSM-5 intellectual disability Substance use disorder (other than opioid, nicotine, or cannabis) within the past 3 months Current, active suicidal ideation with intent or plan Positive urine drug screen for illicit substance use that can increase seizure risk (cocaine, benzodiazepines, amphetamine, methamphetamine) History of psychosis in the past 3 months or diagnosis of a primary psychotic disorder Any history of a progressive or genetic neurologic disorder (e.g. Parkinson’s disease, multiple sclerosis, tuberous sclerosis, Alzheimer’s Disease) or acquired neurological disease (e.g., stroke, traumatic brain injury, tumor), including intracranial lesions History of head trauma resulting in any loss of consciousness (>15 minutes) or neurological sequelae Current history of poorly controlled headaches including chronic medication for migraine prevention History of fainting spells of unknown or undetermined etiology that might constitute seizures History of seizures, diagnosis of epilepsy, or immediate (1st degree relative) family history epilepsy with the exception of a single seizure of benign etiology (e.g., febrile seizures) in the judgment of a board-certified neurologist Chronic uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (e.g., cardiac malformation, cardiac dysrhythmia, asthma, etc.) Any metal in the brain or skull (excluding dental fillings) or elsewhere in the body unless cleared by the responsible covering physician (e.g., MRI compatible joint replacement) Any devices such as pacemaker, medication pump, nerve stimulator, TENS unit, ventriculo-peritoneal shunt unless cleared by the responsible covering physician All female participants of child-bearing age will be required to have a pregnancy test; any participant who is pregnant or planning to become pregnant will not be enrolled in the study Medications will be reviewed by the responsible covering physician and a decision about inclusion will be made based on the participant’s past medical history, drug dose, history of recent medication changes or duration of treatment, and use of CNS active drugs. The published TMS guidelines review of medications to be considered with TMS will be taken into consideration given their described effects on cortical excitability measures Participants who, in the investigator’s opinion, might not be suitable for the study or would be unable to tolerate the study visit Sample size We plan to recruit up to 60 participants at each site (VUMC and SynpaticPSYCH) to obtain a completion sample of n = 50 at each site for a total of n = 100. With 80% power, a type 1 error rate of 5%, and 100 subjects across all sites, we can detect effect sizes larger than 0.40. Based on these calculations, our proposed total sample of n = 100 will provide adequate power to detect changes in craving and opioid use. Recruitment and screening Chart review and team meetings will be used to identify outpatients at the academic medical institution and at the private clinic who meet criteria for the proposed study diagnoses. The research team will speak with the patient’s psychiatrist and that individual will inform the research team whether they believe the patient can comprehend the study and procedures. If they deem the patient can provide informed consent and understand the study, the patient will be approached by someone familiar to them (e.g., a member of their care team) to see if they are willing to discuss participation in this study. If the patient assents, their name will be given to a research staff member who will contact them to schedule a study session. Patients may be pre-screened by phone. Research personnel involved with recruitment will discuss the study with the patient. If the participant meets criteria for the study, they may be scheduled for participation in the study. Research participants may be recruited through inpatient, partial hospital, intensive outpatient, or other clinics. Randomization and blinding procedures Randomization will be stratified by site, with independent allocation sequences generated within each site. Within each stratum, treatment assignments will be generated using a permuted block design to maintain balance between groups throughout enrollment. The study biostatistician (SV) will generate the randomization sequence. As this is a single-blind study, study personnel responsible for administering TMS will have access to the allocation sequence, maintained on a centr
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