Transcranial Magnetic Stimulation for Insomnia

Overseen By William Killgore, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Arizona

Must not be taking: Seizure medications

Disqualifiers: Metal implants, Sleep apnea, Seizures, Substance abuse, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 2-3 weeks

144 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants do not use certain prescription medications that can influence seizure threshold or neuroimaging findings. If you are taking such medications, you may need to stop them to participate.

What data supports the effectiveness of the treatment Transcranial Magnetic Stimulation (TMS) for insomnia?

Research suggests that repetitive transcranial magnetic stimulation (rTMS) can improve sleep quality in people with insomnia, as shown in studies where it helped with sleep issues related to depression and intractable insomnia. A systematic review and meta-analysis also indicate that rTMS might be a promising technique for treating insomnia. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Transcranial magnetic stimulation (TMS), including its variations like repetitive TMS (rTMS) and theta burst stimulation (TBS), is generally considered safe for humans, though there is a small risk of seizures, especially with high-frequency protocols. Most adverse events are mild, but caution and adherence to safety guidelines are recommended. ^{6 7 8 9 10}

How is Transcranial Magnetic Stimulation (TMS) different from other treatments for insomnia?

Transcranial Magnetic Stimulation (TMS) is unique because it uses magnetic fields to stimulate nerve cells in the brain, which can improve sleep quality by decreasing brain activity and remodeling brain connections. Unlike medications, TMS is a non-invasive treatment that does not involve taking drugs, and it may offer long-term benefits even after the treatment stops. ^{1 2 3 4 5}

What is the purpose of this trial?

The investigators propose to expand our previous work to test whether 10 repeated administrations of the cTBS procedure over a two-week period can lead to longer-term improvements in sleep, perhaps up to 3-months. For this 3-year study, 120 people with insomnia will be recruited to participate. There will be an initial screening, with the first consent form being for the screening questions, a psychological interview, and a one night at home sleep monitoring session with our equipment. If participants pass this first phase, they will reconsent for the main portion of the study. They will then undergo a physical examination, then a week-long at-home monitoring phase where they will wear a wristwatch sleep monitor as well as wear a portable brain wave monitor to bed each night to record sleep. Participants will continue to use this equipment throughout the treatment phase and for one week post treatment. After the first monitoring phase, each participant will be randomly assigned to one of four different conditions (i.e., 30 assigned to each group). Three of the conditions will involve cTBS focused on different brain locations (i.e., stimulation to the middle front, middle back, or side of the skull), while the fourth condition will provide inactive sham stimulation as a control. All participants will complete 10 treatment visits to the lab over two-to-three weeks, during which they will get a brief cTBS or sham stimulation each time. In addition, all participants will complete a brain scanning and cognitive testing session at the beginning and end of the two-to-three week treatment period. Participants will also complete 1-month and 3-month online follow-up assessments to examine long-term effects.

Eligibility Criteria

This trial is for individuals suffering from insomnia. Participants must pass an initial screening, including a psychological interview and at-home sleep monitoring. They should be willing to undergo physical exams, wear sleep monitors nightly, and attend 10 lab visits over two-to-three weeks for treatment sessions.

Inclusion Criteria

* Must score in the moderate or higher range on the Insomnia Severity Index (ISI ≥ 15)

* Must meet the criteria for DSM-5 insomnia disorder as determined by a clinical interview with a board-certified sleep medicine physician.

* Sex ratio will be set to \~50% males; \~50% females

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 virtual visit, 1 in-person visit

Pre-Intervention Monitoring

Participants undergo a week-long at-home monitoring phase with sleep and brain wave monitors

1 week

At-home monitoring

Treatment

Participants receive 10 sessions of cTBS or sham stimulation over 2-3 weeks, with cognitive testing and brain scanning

2-3 weeks

10 in-person visits

Post-Intervention Monitoring

Participants continue at-home monitoring for 7 nights and complete a final close-out visit

1 week

1 in-person visit, at-home monitoring

Follow-up

Participants complete online assessments and a psychological interview at 1-month and 3-months post-study

3 months

Online assessments

Treatment Details

Interventions

• Transcranial Magnetic Stimulation (TMS)

Trial Overview The study tests if transcranial magnetic stimulation (TMS) can improve sleep in insomniacs by administering it repeatedly over two weeks. It compares the effects of TMS on different brain areas versus sham (inactive) stimulation to see which leads to better long-term sleep improvements.

Participant Groups

Group I: Active Stimulation - Posterior Cingulate Cortex Active Control 1 Intervention

Active Stimulation targeted at the Posterior Cingulate Cortex

Group II: Active Stimulation - Inferior Parietal Lobule Active Control 1 Intervention

Active Stimulation targeted at the Inferior Parietal Lobule

Group III: Active Stimulation - Dorsomedial Prefrontal Cortex Active Control 1 Intervention

Active Stimulation targeted at the Dorsomedial Prefrontal Cortex

Group IV: Sham Stimulation Placebo Group 1 Intervention

The TMS device will be placed to the head but no energy will be emitted.

Transcranial Magnetic Stimulation (TMS) is already approved in United States, European Union for the following indications:

Approved in United States as Transcranial Magnetic Stimulation (TMS) for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Migraine Headache Symptoms

Approved in European Union as Transcranial Magnetic Stimulation (TMS) for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)

Who Is Running the Clinical Trial?

University of Arizona

Lead Sponsor

Trials

545

Recruited

161,000+

U.S. Army Medical Research Acquisition Activity

Collaborator

Trials

26

Recruited

10,500+

Findings from Research

In a study of 165 pediatric participants aged 6 to 18, theta-burst TMS (TBS) demonstrated a similar safety profile to single- and paired-pulse TMS (sp/ppTMS), with no severe adverse effects reported.

The overall rate of adverse effects was 10.5% for TBS and 12.4% for sp/ppTMS, with most effects rated as minimal or mild, indicating that TBS is a safe option for further investigation in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects. Hong, YH., Wu, SW., Pedapati, EV., et al.[2020]

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]

Theta burst stimulation (TBS) is a promising technique for altering brain excitability, with a review of studies showing that adverse events were mostly mild and occurred in only 5% of subjects, indicating a generally safe profile.

Despite its safety, TBS carries a theoretical higher risk of seizures compared to other stimulation methods, necessitating cautious application and further research into its dosing parameters to better understand seizure risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. Oberman, L., Edwards, D., Eldaief, M., et al.[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]

In a safety and efficacy study involving a 26-year-old man with severe traumatic brain injury (TBI), a 6-week rTMS protocol showed no adverse events, indicating it is a safe treatment option for individuals in a minimally conscious state.

The rTMS treatment was associated with a trend toward significant neurobehavioral improvements and enhanced neural conduction, suggesting its potential to facilitate recovery in patients with severe TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation-associated neurobehavioral gains during coma recovery. Louise-Bender Pape, T., Rosenow, J., Lewis, G., et al.[2016]

References

1. Poland pubmed.ncbi.nlm.nih.gov

The influence of the repetitive transcranial magnetic stimulation on sleep quality in depression. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

The long-term effect of repetitive transcranial magnetic stimulation in the treatment of intractable insomnia. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Altered response to repetitive transcranial magnetic stimulation in patients with chronic primary insomnia. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Electroencephalographic connectivity predicts clinical response to repetitive transcranial magnetic stimulation in patients with insomnia disorder. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

The effect of repetitive transcranial magnetic stimulation for insomnia: a systematic review and meta-analysis. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects. [2020]

7. 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]

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

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. [2022]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

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

Repetitive transcranial magnetic stimulation-associated neurobehavioral gains during coma recovery. [2016]