rTMS for Stimulant Addiction

(VA-StARTS Trial)

Overseen By Jong H Yoon, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Must not be taking: Clozapine, Chlorpromazine, Clomipramine, Bupropion

Disqualifiers: Pregnancy, Seizures, Severe psychosis, others

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: 1

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called repetitive transcranial magnetic stimulation (rTMS) for Veterans dealing with stimulant addiction. The goal is to determine if rTMS can be an effective option, as no widely recognized treatments currently exist for this condition. Participants will receive either real rTMS or a sham (fake) treatment for comparison. Veterans diagnosed with severe stimulant use disorder, who have been off stimulants for more than a week but less than six weeks, might be suitable candidates. They must also have a stable living situation to attend clinic visits regularly. As an unphased trial, this study offers Veterans a unique opportunity to contribute to pioneering research in developing new treatment options for stimulant addiction.

Will I have to stop taking my current medications?

The trial requires that your medication regimen remains stable, meaning you should not change the dose or type of medications you are taking from two weeks before the study starts and throughout the treatment phase. However, if you are on certain medications that lower the seizure threshold or are direct dopaminergic agents, you may need to stop those.

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

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is generally a safe treatment. Studies have found that most patients tolerate rTMS well, with few reports of serious side effects. Some individuals might experience mild discomfort or headaches during the treatment, but these typically subside shortly after the session. The treatment uses magnetic fields to stimulate nerve cells in the brain. Despite sounding complex, it is a non-invasive procedure.

Although the results are promising, researchers continue to study the effectiveness of rTMS for treating stimulant use disorder. So far, the safety data is encouraging, suggesting it could be a viable option for those seeking help with addiction. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for stimulant addiction, which often rely on behavioral therapy and medications like naltrexone or bupropion, repetitive transcranial magnetic stimulation (rTMS) uses magnetic fields to stimulate nerve cells in the brain. This non-invasive technique is exciting to researchers because it directly targets brain areas involved in addiction, which could offer a new way to reduce cravings and improve self-control. Additionally, rTMS has the potential to provide benefits more quickly and with fewer side effects than traditional medication-based approaches.

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

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can help reduce cravings in people addicted to stimulants. Studies have found that rTMS significantly lowers cravings and risky behaviors related to substance use. In this trial, participants will be assigned to different treatment arms: some will receive active rTMS, which has shown a strong effect in reducing craving scores, while others will receive sham rTMS for comparison. Overall, rTMS appears to be a promising option for treating stimulant addiction by targeting the brain areas involved in cravings and self-control. ^{1 2 3 6 7}

Who Is on the Research Team?

Jong H. Yoon, MD

Principal Investigator

VA Palo Alto Health Care System, Palo Alto, CA

Are You a Good Fit for This Trial?

This trial is for Veterans with severe stimulant use disorder (SUD) who have not used stimulants for 1-6 weeks. Participants must be able to undergo cognitive tests, fMRI scans, and rTMS treatment without contraindications, have an IQ over 80, a stable medication regimen and living situation. Exclusions include incompatible implants or devices, unstable medical/psychiatric conditions, other active substance disorders (except PTSD), pregnancy/lactation, prior adverse reaction to TMS or medications lowering seizure threshold.

Inclusion Criteria

Stable social environment and housing to enable regular attendance at clinic visits

Stable medication regimen (no change in dose or agents between 2 weeks prior to the start of and throughout the treatment phase of the study)

Ability to undergo cognitive testing, fMRI scans, and rTMS (no contraindications)

Exclusion Criteria

Pregnant or lactating female

You have implants or medical devices that cannot be used with TMS (Transcranial Magnetic Stimulation).

You have had a bad reaction to TMS treatment in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either active or sham repetitive transcranial magnetic stimulation (rTMS) for stimulant use disorder

2 weeks

Daily visits for rTMS sessions

Follow-up

Participants are monitored for relapse rate, occupational functioning, and rest/activity cycles after rTMS treatment

3 months

Visits at 1 week, midpoint, and 3 months post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Repetitive transcranial magnetic stimulation (rTMS)

Trial Overview The study is testing repetitive transcranial magnetic stimulation (rTMS) as a potential new treatment for SUD in Veterans. It aims to establish the feasibility of rTMS application in this population and evaluate its effectiveness while identifying biomarkers that could predict which patients will benefit most from this therapy.

How Is the Trial Designed?

Group I: Active rTMS Experimental Treatment 1 Intervention

Receive active rTMS

Group II: Sham rTMS Placebo Group 1 Intervention

Receive sham rTMS

Repetitive transcranial magnetic stimulation (rTMS) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Migraine prevention

Approved in European Union as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder

Approved in Canada as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

A review of 18 clinical trials found that repetitive transcranial magnetic stimulation (rTMS) is effective in reducing cravings associated with various addictions, particularly in the short term.

Most studies used a Visual Analogue Scale to measure craving, highlighting the need for standardized assessment methods to improve the reliability of rTMS efficacy results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of repetitive transcranial magnetic stimulation for modulating craving and addictive behaviours: a critical literature review of efficacy, technical and methodological considerations. Grall-Bronnec, M., Sauvaget, A.[2015]

Repetitive transcranial magnetic stimulation (rTMS) shows promise as a non-invasive treatment for cocaine and methamphetamine use disorders by potentially inducing beneficial changes in brain circuits related to addiction, particularly affecting dopamine and glutamate systems.

Clinical studies indicate that rTMS can alter brain network connectivity, which may help reduce cravings in individuals with substance use disorders, suggesting a new avenue for effective treatment where no FDA-approved options currently exist.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders. Moretti, J., Poh, EZ., Rodger, J.[2020]

Transcranial magnetic stimulation (TMS) has been explored in 19 studies involving 316 adults for its potential to reduce drug cravings and use, particularly targeting the dorsolateral prefrontal cortex with high-frequency pulses.

While some studies showed promising results, such as decreased smoking and cocaine use, the treatment is still experimental, and the exact mechanisms and optimal parameters for rTMS in addiction treatment remain unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in the treatment of substance addiction. Gorelick, DA., Zangen, A., George, MS.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[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]

Low-frequency repetitive transcranial magnetic stimulation (rTMS) effectively blocked methamphetamine-induced conditioned place preference in rats, suggesting its potential to inhibit the development of methamphetamine addiction.

The mechanism behind this effect involves a downregulation of GABABR1 expression in the dorsolateral striatum, indicating a specific neurobiological target for rTMS in treating drug addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-frequency repetitive transcranial magnetic stimulation inhibits the development of methamphetamine-induced conditioned place preference. Wu, XQ., Zan, GY., Ju, YY., et al.[2019]

Repetitive Transcranial Magnetic Stimulation (rTMS) has shown promising efficacy in treating various addictions, with strong evidence for nicotine addiction (effective in 218 out of 289 subjects) and moderate evidence for alcohol and cocaine addictions, indicating its potential as a therapeutic tool.

Despite its effectiveness, the current evidence for rTMS in treating other addictions like heroin and methamphetamine is limited, highlighting the need for further research to understand its mechanisms and improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Repetitive Transcranial Magnetic Stimulation (rTMS) in Treatment of Addiction and Related Disorders: A Systematic Review. Makani, R., Pradhan, B., Shah, U., et al.[2018]

A multicenter double-blind RCT involving 262 chronic smokers showed that repetitive transcranial magnetic stimulation (rTMS) significantly increased the continuous quit rate (CQR) to 19.4% compared to 8.7% for the sham treatment, indicating its efficacy in promoting smoking cessation.

This study established a safe treatment protocol for rTMS, which has now received FDA clearance as an aid for smoking cessation, marking a significant advancement in addiction medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for smoking cessation: a pivotal multicenter double-blind randomized controlled trial. Zangen, A., Moshe, H., Martinez, D., et al.[2021]

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 study involving 10 treatment-seeking cocaine addicts, bilateral repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex did not show a statistically significant difference in cocaine intake compared to sham treatment over time.

However, exploratory analysis revealed a trend towards reduced cocaine consumption in the active rTMS group, with significant reductions observed at 3 months and at the end of treatment, suggesting potential long-term benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral Transcranial Magnetic Stimulation of the Prefrontal Cortex Reduces Cocaine Intake: A Pilot Study. Bolloni, C., Panella, R., Pedetti, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8836499/

Repetitive Transcranial Magnetic Stimulation (rTMS) as a ... Repetitive transcranial magnetic stimulation (rTMS) as a promising treatment for craving in stimulant drugs and behavioral addiction: a meta-analysis.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9197111/

Efficacy of Repetitive Transcranial Magnetic Stimulation in ... The positive SMD results indicated the improvement of clinical symptoms after the treatment with add-on rTMS. rTMS showed a more significant effect than the ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2451902225001259

Deep Transcranial Magnetic Stimulation Efficacy in ... The results showed a significant and large effect of real dTMS in reducing craving scores (SMCC = −1.26; 95% CI, −1.67 to −0.86; p < .001). High ...

4. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05940-z

Efficacy of repetitive transcranial magnetic stimulation (rTMS ... Several studies have observed a beneficial effect of rTMS on substance use disorders by reducing craving, impulsivity, and risk-taking behavior ...

5. 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)

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12060337/

Repetitive transcranial magnetic stimulation for stimulant use ... The study is a double-blind, sham-controlled trial seeking to recruit 160 participants with a current moderate to severe CcUD or MtUD diagnosis.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06960265

Effects of Repetitive Transcranial Magnetic Stimulations in ... The study aims to better understand how rTMS might help reduce amphetamine cravings and improve outcomes, potentially leading to new treatment ...