rTMS for Opioid Use Disorder

Overseen By Gregory Sahlem

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Must be taking: Buprenorphine

Must not be taking: Alcohol, Sedatives

Disqualifiers: Pregnancy, Psychotic disorder, Bipolar, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 24

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assist individuals with opioid use disorder who are beginning buprenorphine treatment and wish to stop using opioids. Researchers are investigating whether a brain scan (MRI) can predict successful cessation and if repetitive Transcranial Magnetic Stimulation (rTMS) is more effective than a placebo. Participants will undergo brain scans and receive either real or sham rTMS sessions over several weeks. This trial suits those planning to quit opioids and start buprenorphine treatment. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research that could enhance future treatment strategies for opioid use disorder.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have an unstable condition that requires starting a new medication, you may not be eligible to participate.

What prior data suggests that rTMS is safe for treating opioid use disorder?

Research has shown that repetitive Transcranial Magnetic Stimulation (rTMS) is generally safe and well-tolerated. Studies have found it can help reduce cravings in people with opioid use disorder, indicating its safety. Most people undergo rTMS without serious side effects, though some might experience mild discomfort, such as headaches or scalp irritation. These effects typically resolve on their own. Importantly, rTMS is already used for other conditions, like depression and chronic pain, suggesting a strong safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using repetitive Transcranial Magnetic Stimulation (rTMS) for opioid use disorder because it offers a non-invasive approach that directly targets brain activity. Unlike traditional treatments like medication-assisted therapy (e.g., methadone, buprenorphine) which focus on managing withdrawal symptoms and reducing cravings through chemical means, rTMS uses magnetic fields to stimulate specific areas of the brain. This technique could potentially recalibrate brain circuits associated with addiction, offering a novel mechanism of action that might enhance recovery outcomes. Additionally, rTMS can be administered in a relatively short time frame, with flexibility in scheduling, which may improve adherence and accessibility for patients.

What evidence suggests that rTMS might be an effective treatment for opioid use disorder?

Research has shown that repetitive Transcranial Magnetic Stimulation (rTMS) might help reduce cravings for opioids. In this trial, participants will join either an active rTMS treatment arm or a sham rTMS arm. Some studies have found that rTMS can decrease the urge to use opioids, even after treatment sessions conclude. Early evidence suggests that applying rTMS to specific brain areas reduces cravings in individuals with opioid use disorder. One study discovered that targeting rTMS to the left dorsolateral prefrontal cortex, a brain area involved in decision-making and self-control, specifically reduces cravings triggered by reminders of drug use. Overall, rTMS appears to be a promising tool for managing opioid cravings. ^{2 4 6 7 8}

Who Is on the Research Team?

Gregory Sahlem, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for individuals with Opioid Use Disorder who are starting buprenorphine treatment to quit opioids. Participants will undergo MRI scans and receive either real or placebo rTMS sessions, while their opioid abstinence is monitored over a 12-week period.

Inclusion Criteria

I have been diagnosed with moderate or severe opioid use disorder, and opioids are my main substance of use.

Intellectual level sufficient to provide informed consent and accurately complete assessment instruments (English speaking/writing)

I am starting buprenorphine and plan to stop using opioids.

Exclusion Criteria

Contraindications to receiving rTMS or undergoing MRI (implanted ferromagnetic metal, history of or high risk of seizure, implanted device)

I have been diagnosed with bipolar disorder.

I need to start a new medication for an unstable mental health condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

MRI Assessment

Participants complete an MRI within 5 days of starting buprenorphine and again after they are on a full stable dose 1-3 weeks later

1-3 weeks

2 visits (in-person)

rTMS Treatment

Participants undergo 50 sessions of either real or placebo rTMS over 1 to 6 weeks

1-6 weeks

10 sessions per week (in-person)

Follow-up

Participants are monitored for opioid abstinence and relapse over a 12-week period

12 weeks

12 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Repetitive Transcranial Magnetic Stimulation (rTMS)

Trial Overview The study aims to determine if an MRI brain marker can predict successful quitting with buprenorphine and whether adding repetitive Transcranial Magnetic Stimulation (rTMS) improves the chances of quitting opioids compared to a sham version of rTMS.

How Is the Trial Designed?

Group I: Low Ventral Striatal Reactivity Experimental Treatment 1 Intervention

We will test for ventral striatal reactivity using a Reassessment of Craving MRI task and define low ventral striatal reactivity as having \< mean voxels in the ventral striatum activate

Group II: High Ventral Striatal Reactivity Experimental Treatment 1 Intervention

We will test for ventral striatal reactivity using a Reassessment of Craving MRI task and define high ventral striatal reactivity as having \>mean voxels in the ventral striatum activate

Group III: Active rTMS Experimental Treatment 1 Intervention

A total of 30-sessions of standard iTBS (1800 pulses) will be delivered. rTMS-sessions will be ideally administered over 1-week (10-sessions-per-day, 50-minutes inter-session-interval, 5-days), but there will be flexibility in the delivery paradigm so long as participants complete all sessions of rTMS within 6 weeks and come in at least twice per week.

Group IV: Sham rTMS Placebo Group 1 Intervention

Double-blind sham-rTMS in an identical fashion to the active-rTMS condition will be delivered.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

In a randomized clinical trial with 30 methamphetamine-addicted patients, real rTMS significantly reduced cue-induced craving after 5 sessions compared to sham stimulation.

Real rTMS also improved cognitive functions such as verbal learning and memory, indicating it is a safe and effective intervention for reducing cravings in methamphetamine addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex for methamphetamine use disorders: A randomised clinical trial. Su, H., Zhong, N., Gan, H., et al.[2022]

In a pilot trial involving 22 participants with opioid use disorder undergoing methadone maintenance therapy, repetitive transcranial magnetic stimulation (rTMS) did not significantly reduce cravings or heroin use compared to a sham treatment.

However, rTMS was associated with significant improvements in depressive symptoms, impulse control, and attention, suggesting potential benefits for mental health aspects in individuals with opioid use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Add-on repetitive transcranial magnetic stimulation in patients with opioid use disorder undergoing methadone maintenance therapy. Tsai, TY., Wang, TY., Liu, YC., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) has shown effectiveness in reducing cravings for tobacco, alcohol, and cocaine when applied at high frequencies to the dorsolateral prefrontal cortex (DLPFC), based on a review of eight studies.

Repeated sessions of high-frequency rTMS over the DLPFC may be particularly beneficial for decreasing smoking and alcohol consumption, suggesting that rTMS could be a promising treatment option for drug addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation and drug addiction. Barr, MS., Farzan, F., Wing, VC., et al.[2019]

Excitatory repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral pre-frontal cortex significantly reduces craving for substances in patients with dependence, with a strong effect size (Hedges' g = -0.62) based on a meta-analysis of 26 randomized controlled trials involving 748 participants.

In addition to reducing cravings, rTMS also effectively decreases substance consumption, particularly when using excitatory stimulation protocols, indicating its potential as a therapeutic intervention for substance dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of repetitive transcranial magnetic stimulation (rTMS) on craving and substance consumption in patients with substance dependence: a systematic review and meta-analysis. Zhang, JJQ., Fong, KNK., Ouyang, RG., et al.[2020]

Repetitive transcranial magnetic stimulation (rTMS) shows promise as a noninvasive treatment for substance use disorders (SUDs) like cocaine and opioid use disorders by inducing neuroplastic changes in the brain, which can help reduce cravings and drug use.

The field faces several 'known unknowns' that need to be addressed to optimize rTMS for SUDs, including selecting the right cortical targets, understanding subcortical circuit engagement, and determining the best treatment sequences, highlighting the need for collaborative research efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating cocaine and opioid use disorder with transcranial magnetic stimulation: A path forward. Steele, VR., Maxwell, AM.[2023]

Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool that can effectively treat clinical depression and potentially other brain disorders, but it carries risks, including the potential to induce seizures, as evidenced by 7 known cases by 1996.

A workshop established safety guidelines for rTMS, emphasizing the importance of monitoring, ethical considerations, and the expertise required for its administration to minimize risks and enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Wassermann, EM.[2022]

Repetitive transcranial magnetic stimulation (rTMS) shows promise as a novel intervention for opioid use disorder (OUD), with a case report indicating a significant reduction in cravings for heroin and cocaine by approximately 60% to 82% after 7 sessions targeting the left dorsolateral prefrontal cortex.

This case highlights the potential of rTMS to augment medication-assisted treatment (MAT) for individuals with OUD, especially for those who continue to experience cravings despite comprehensive treatment, suggesting a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case report illustrating the effects of repetitive transcranial magnetic stimulation on cue-induced craving in an individual with opioid and cocaine use disorder. Mahoney, JJ., Marshalek, PJ., Rezai, AR., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39545446/

Repetitive transcranial magnetic stimulation in the ... TMS has been seen in some studies to significantly reduce cravings for opioids with effects beyond the last administrated treatment.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2352396420301845

The effects of repetitive transcranial magnetic stimulation ... Early evidence suggests that repetitive transcranial magnetic stimulation is effective in reducing cue induced craving for patients with opioid use disorder ( ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06689072?term=rtms&viewType=Table&rank=1

Role of High Frequency RTMS in Management of Opioid ... This study aims to evaluate the role of repetitive Transcranial Magnetic Stimulation ( rTMS ) applied to the left dorsolateral prefrontal cortex (DLPFC) in ...

4. mdpi.com mdpi.com/2077-0383/11/3/624

Repetitive Transcranial Magnetic Stimulation (rTMS) as a ... This meta-analysis uses updated evidence to assess overall rTMS efficacy on craving, differential effects between addiction types clustered into three groups.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7037539/

A Case Report Illustrating the Effects of Repetitive ... The one published study on the use of repetitive TMS (rTMS) for OUD found that a single session of rTMS to the left DLPFC reduced cue-induced craving in long- ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK566938/

Evidence Brief: Transcranial Magnetic Stimulation (TMS) for ... The goal of this review is to synthesize important and recent evidence on TMS effectiveness and safety for treatment of chronic pain, PTSD, TBI, opioid ...

7. nature.com nature.com/articles/s41386-023-01776-0

A systematic review and meta-analysis of neuromodulation ... Ninety-four studies were identified that examined the effects of rTMS, tDCS, and DBS on substance use outcomes (eg, craving, consumption, and relapse)

8. hsrd.research.va.gov hsrd.research.va.gov/publications/management_briefs/default.cfm?ManagementBriefsMenu=eBrief-no180&eBriefTitle=Evidence+Brief%3A+Transcranial+Magnetic+Stimulation+%28TMS%29+for+Chronic+Pain%2C+PTSD%2C+TBI%2C+Opioid+Addiction%2C+and+Sexual+Trauma++

Transcranial Magnetic Stimulation (TMS) for Chronic Pain ... rTMS therapy may reduce symptoms in people with chronic pain, post-traumatic stress disorder (PTSD), traumatic brain injury (TBI), and opiate addiction.