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

Trial Summary

What is the purpose of this trial?

In this research study the investigators will work with 80-participants with opioid use disorder who are starting treatment with the medication buprenorphine and are trying to quit using opioids. The investigators are trying to learn two things: 1. Can an MRI brain marker be used to predict which participants will be successful in quitting opioids with buprenorphine? 2. Does adjunctive treatment with repetitive Transcranial Magnetic Stimulation (rTMS) help people quit using opioids more than a sham (placebo) version of rTMS? In order to complete the study the investigators will ask participants to: * Complete an MRI within 5-days of starting buprenorphine and again after they are on a full stable dose 1-3 weeks later. * Undergo study-treatment with 50-sessions of either real or placebo rTMS in as little as 1-week (10-sessions-per-day for five days) or as long as over 6-weeks. * Meet with the investigators once per week over the following 12-weeks to see if the participants have been able to quit using opioids over that time.

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 data supports the effectiveness of the treatment Repetitive Transcranial Magnetic Stimulation (rTMS) for opioid use disorder?

Research suggests that rTMS may help reduce cravings and improve symptoms like depression and impulse control in people with opioid use disorder, although it did not significantly reduce heroin use in one study. Additionally, rTMS has shown promise in reducing cravings for other substances like tobacco, alcohol, and cocaine, indicating its potential as a treatment for various addictions. ^{1 2 3 4 5}

Is repetitive transcranial magnetic stimulation (rTMS) safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe for humans, but it has been associated with some risks, such as seizures. Guidelines have been developed to ensure its safe use, including limits on stimulation parameters and monitoring of participants. ^{1 2 3 6 7}

How does rTMS treatment differ from other treatments for opioid use disorder?

Repetitive transcranial magnetic stimulation (rTMS) is a unique treatment for opioid use disorder because it is a non-invasive method that uses magnetic fields to stimulate specific areas of the brain, potentially reducing cravings and improving symptoms like depression and impulsivity. Unlike traditional medication-assisted treatments, rTMS targets brain circuits directly and may be used alongside existing therapies to enhance their effectiveness. ^{1 2 3 4 7}

Research Team

Gregory Sahlem, MD

Principal Investigator

Duke University

Eligibility Criteria

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

I have been diagnosed with bipolar disorder.

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

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

Timeline

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)

Treatment Details

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.

Participant Groups

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 50-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+

Findings from Research

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) 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) 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Add-on repetitive transcranial magnetic stimulation in patients with opioid use disorder undergoing methadone maintenance therapy. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Treating cocaine and opioid use disorder with transcranial magnetic stimulation: A path forward. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation and drug addiction. [2019]

4. England 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. [2020]

5. Ireland 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. [2022]

6. Ireland 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. [2022]

7. United States 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. [2021]