Pilot TMS for Methamphetamine Use Disorder

Overseen By Ryan Carnahan, PharmD, MS

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Iowa

Must not be taking: Clozapine, Stimulants

Disqualifiers: Epilepsy, Schizophrenia, Neurological disorder, others

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

Compensation: Varies

Number of Visits: 16

Duration: 4 weeks

19 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new magnetic pulse treatment for people struggling with methamphetamine addiction. The treatment targets specific brain areas to help reduce cravings and improve self-control. It aims to see if this method can be more effective than typical treatments.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically clozapine or stimulants, if you are currently on them.

What data supports the effectiveness of the treatment Dual Target Transcranial Magnetic Stimulation?

Research shows that transcranial magnetic stimulation (TMS), a non-invasive brain stimulation technique, can be effective in treating depression, including in cases where other treatments have failed. The effectiveness of TMS can depend on targeting specific brain circuits related to symptoms, which suggests that dual targeting might enhance its benefits. ^{1 2 3 4 5}

Is Dual Target Transcranial Magnetic Stimulation generally safe for humans?

Transcranial Magnetic Stimulation (TMS), including Dual Target TMS, is generally considered safe, but it can cause mild side effects like headaches and nausea. There is a small risk of seizures, and while long-term effects are not fully understood, most studies show a reassuring safety profile. ^{6 7 8 9 10}

How does Dual Target Transcranial Magnetic Stimulation differ from other treatments?

Dual Target Transcranial Magnetic Stimulation is unique because it uses magnetic pulses to stimulate two different brain areas simultaneously, allowing researchers to explore the interactions between these areas and potentially reshape brain connectivity. This approach is non-invasive and can be adjusted to target specific brain regions, offering a novel way to treat neurological and psychiatric conditions by enhancing or modifying brain activity. ^{5 11 12 13 14}

Research Team

Ryan Carnahan, PharmD, MS

Principal Investigator

University of Iowa

Alison C Lynch, MD, MS

Principal Investigator

University of Iowa

Eligibility Criteria

Inclusion Criteria

Diagnosed with an active methamphetamine use disorder

Is engaged in psychosocial treatment or articulates a plan to engage in psychosocial treatment for methamphetamine use disorder during the study period

Able to consent for treatment and research participation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dual target transcranial magnetic stimulation (TMS) daily for 2 weeks, followed by three times weekly for 2 weeks

4 weeks

16 sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of depressive symptoms, anxiety, sleep, craving, quality of life, and methamphetamine use

12 weeks

Monthly follow-up visits

Treatment Details

Interventions

• Dual Target Transcranial Magnetic Stimulation

Participant Groups

Group I: MPFC first Experimental Treatment 1 Intervention

Participants in this arm will undergo all study procedures including consent; pre-, during, and post-psychological assessments; pre- and post- MRI and fMRI; 16 treatments of dual target TMS over a 4-week period; and substance use-related assessments to include substance use, withdrawal symptoms, and cravings to use. This arm will receive the medial prefrontal cortex stimulation first.

Group II: DPFC first Experimental Treatment 1 Intervention

Participants in this arm will undergo all study procedures including consent; pre-, during, and post-psychological assessments; pre- and post- MRI and fMRI; 16 treatments of dual target TMS over a 4-week period; and substance use-related assessments to include substance use, withdrawal symptoms, and cravings to use. This arm will receive the dorsolateral prefrontal cortex stimulation first.

Who Is Running the Clinical Trial?

University of Iowa

Lead Sponsor

Trials

486

Recruited

934,000+

Ryan M. Carnahan

Lead Sponsor

Trials

2

Recruited

44,500+

University of New Mexico

Collaborator

Trials

393

Recruited

3,526,000+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

Findings from Research

In a study involving 49 patients with bipolar disorder and treatment-resistant depression, sequential bilateral repetitive transcranial magnetic stimulation (rTMS) did not show a significant difference in reducing depression scores compared to sham stimulation.

The findings suggest that active sequential bilateral rTMS may not be effective for treating bipolar depression, indicating a need for future research to explore unilateral rTMS approaches instead.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A negative double-blind controlled trial of sequential bilateral rTMS in the treatment of bipolar depression. Fitzgerald, PB., Hoy, KE., Elliot, D., et al.[2019]

Transcranial magnetic stimulation (TMS) is a non-invasive and painless method used since 1985 to stimulate the brain and cranial nerves, with applications in both diagnostics and treatment.

Repetitive TMS can modify the excitability of the cerebral cortex, making it a promising therapeutic tool for investigating neural circuitry and treating various neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in clinical practice. Alisauskiene, M., Truffert, A., Vaiciene, N., et al.[2018]

Mild adverse effects (MAEs) from transcranial magnetic stimulation (TMS) occur in about 5% of sessions, with most symptoms like headache and nausea reported after the sessions, particularly during initial treatments.

The study found no significant links between participant characteristics (age and gender) or TMS parameters (frequency and intensity) and the occurrence of MAEs, suggesting that initial participant anxiety may play a role in these reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative incidence rates of mild adverse effects to transcranial magnetic stimulation. Maizey, L., Allen, CP., Dervinis, M., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has not been thoroughly studied for side effects, with the main known risk being the acute production of seizures.

While tissue damage from rTMS is unlikely, there are concerns about potential cognitive effects and the possibility of long-term changes in brain function that have not yet been fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of repetitive transcranial magnetic stimulation. Wassermann, EM.[2005]

Transcranial magnetic stimulation (TMS) has a very low seizure risk, with only 0.08 seizures reported per 1,000 sessions, and less than 0.02 seizures per 1,000 sessions when guidelines are followed for individuals without known risk factors.

The study found that exceeding safety guidelines increases the risk of seizures, and seizures are more likely to occur during the first few TMS sessions, suggesting that TMS is generally safe when administered properly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. Lerner, AJ., Wassermann, EM., Tamir, DI.[2021]

In a meta-analysis of 93 randomized controlled trials involving repetitive transcranial magnetic stimulation (TMS), the overall incidence of adverse events (AEs) was found to be higher in the active TMS group (29.3%) compared to the placebo group (13.6%), indicating a 2.60 times greater risk of experiencing AEs with active treatment.

Despite the higher incidence of AEs, TMS is considered a safe and well-tolerated intervention, with common side effects including headache and dizziness, highlighting the importance of recognizing nocebo effects in both clinical trials and practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Nocebo Phenomena During Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Placebo-Controlled Clinical Trials. Zis, P., Shafique, F., Hadjivassiliou, M., et al.[2022]

In a study of 63 obese individuals undergoing a 5-week rTMS treatment for weight control, the treatment showed a reassuring safety profile with no unexpected adverse events reported up to one year after treatment.

The most common side effects were moderate headaches (40.4%) and local pain/discomfort (19.2%), particularly more frequent in the high-frequency rTMS group, but overall, rTMS was well tolerated in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of repeated sessions of deep transcranial magnetic stimulation in obesity. Ferrulli, A., Massarini, S., Macrì, C., et al.[2021]

The study introduces a novel electronic targeting method for transcranial magnetic stimulation (TMS) using a set of overlapping coils, allowing for faster and more precise stimulation of specific brain areas without the need for physical coil movement.

With just two coils, the device can adjust the stimulation location along a 30-mm line in the cortex, demonstrating a significant advancement in TMS technology that could enhance research and therapeutic applications in brain stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-locus transcranial magnetic stimulation-theory and implementation. Koponen, LM., Nieminen, JO., Ilmoniemi, RJ.[2019]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

A negative double-blind controlled trial of sequential bilateral rTMS in the treatment of bipolar depression. [2019]

2. Canada pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for the treatment of major depressive disorder: an evidence-based analysis. [2023]

3. Croatia pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Transcranial Magnetic Stimulation in Treatment-Resistant Bipolar Depression. [2022]

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

Targeting symptom-specific networks with TMS. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in clinical practice. [2018]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Comparative incidence rates of mild adverse effects to transcranial magnetic stimulation. [2022]

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

Side effects of repetitive transcranial magnetic stimulation. [2005]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. [2021]

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

Safety, Tolerability, and Nocebo Phenomena During Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Placebo-Controlled Clinical Trials. [2022]

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

Safety and tolerability of repeated sessions of deep transcranial magnetic stimulation in obesity. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Tickling the brain: studying visual sensation, perception and cognition by transcranial magnetic stimulation. [2019]

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

Multi-locus transcranial magnetic stimulation-theory and implementation. [2019]

13. Germany pubmed.ncbi.nlm.nih.gov

Cortico-cortical connectivity: the road from basic neurophysiological interactions to therapeutic applications. [2021]

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

Null results in TMS: from absence of evidence to evidence of absence. [2013]