rTMS for Gulf War Syndrome

Recruiting at 2 trial locations

Overseen By Caleb T Lopez, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: Pregnancy, Pacemaker, Dementia, Seizure, 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: Unknown

Duration: 3 months

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This study aims to look at the effectiveness of using repetitive transcranial magnetic stimulation (rTMS) in relieving pain and other co-morbid symptoms of Gulf War Illness.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Repetitive transcranial magnetic stimulation (rTMS) has been studied for safety in both healthy individuals and those with various brain conditions. While generally considered safe, it can cause side effects like seizures, especially at high intensities, and temporary hearing changes. Safety guidelines have been developed to minimize risks, and these guidelines have been updated over the years to ensure safe use. ^{1 2 3 4 5}

How is the treatment rTMS unique for Gulf War Syndrome?

rTMS (Repetitive Transcranial Magnetic Stimulation) is unique for Gulf War Syndrome because it is a non-invasive treatment that uses magnetic fields to stimulate specific areas of the brain, which is different from traditional drug therapies. This method has been used for other conditions like depression and brain injury, offering a novel approach by directly targeting brain activity without medication. ^{4 6 7 8 9}

What data supports the effectiveness of the treatment rTMS for Gulf War Syndrome?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can help reduce symptoms in conditions like PTSD, depression, and chronic pain, which are similar to symptoms experienced in Gulf War Syndrome. For example, rTMS has been effective in reducing PTSD symptoms in veterans and improving depressive symptoms in military personnel. ^{10 11 12 13 14}

Research Team

Albert Yick Leung, MD

Principal Investigator

VA San Diego Healthcare System, San Diego, CA

Eligibility Criteria

This trial is for Gulf War veterans under 65 who experience weekly headaches, muscle and joint pain, meet specific GWI criteria, and have a certain level of depression. It's not for those with pacemakers, metal in their body that affects MRI scans, major psychiatric conditions, other chronic pain states, history of seizures or brain injury.

Inclusion Criteria

Kansas Criteria for GWVI (GWI)

CDC Criteria for GWVI (GWI)

I experience severe headaches weekly that last more than an hour.

Exclusion Criteria

I am currently receiving therapy for my memory/thinking or PTSD.

I suffer from chronic tension or cluster headaches.

Pending litigation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive repetitive transcranial magnetic stimulation (rTMS) to alleviate pain and co-morbid symptoms of Gulf War Illness

3 months

Weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Monthly visits

Treatment Details

Interventions

• rTMS
• Sham Transcranial Magnetic Stimulation

Trial Overview The study tests if repetitive transcranial magnetic stimulation (rTMS) can reduce pain and related symptoms in Gulf War Illness. Participants will receive either real rTMS or a sham (fake) treatment to compare effectiveness.

Participant Groups

Group I: Active rTMS at the LDLPFC Active Control 1 Intervention

Subjects will receive the repetitive Transcranial Magnetic Stimulation (rTMS) study procedure at the left dorsolateral prefrontal cortex (LDLPFC).

Group II: Active rTMS at the LMC Active Control 1 Intervention

Subjects will receive the repetitive Transcranial Magnetic Stimulation (rTMS) study procedure at the left motor cortex (LMC)

Group III: Sham rTMS at the LDLPFC Placebo Group 1 Intervention

Sham rTMS will appear the same as the active, with the same parameters, but will not receive the actual magnetic stimulation to the LDLPFC.

Group IV: Sham rTMS at the LMC Placebo Group 1 Intervention

Sham rTMS will appear the same as the active, with the same parameters, but will not receive the actual magnetic stimulation to the LMC.

rTMS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder
• Migraines
• Smoking cessation

Approved in European Union as rTMS for:

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

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

Repetitive transcranial magnetic stimulation (rTMS) has been found to be safe for military service members with concussions, showing no reports of seizures or increased adverse events compared to general rTMS studies.

However, the evidence supporting the effectiveness of rTMS in treating neuropsychiatric and neurocognitive symptoms following concussions is currently limited, indicating a need for more comprehensive research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Repetitive Transcranial Magnetic Stimulation in the Treatment of Neuropsychiatric and Neurocognitive Symptoms Associated With Concussion in Military Populations. Oberman, LM., Exley, S., Philip, NS., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) significantly reduced headache intensity in veterans with mild traumatic brain injury (MTBI), with a 56.3% reduction in the REAL group compared to 15.4% in the SHAM group after one week.

The treatment was clinically feasible and effective, with 58.3% of the REAL group experiencing at least a 50% reduction in headache intensity, and a significant decrease in overall headache-related disability observed at the four-week assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation in Managing Mild Traumatic Brain Injury-Related Headaches. Leung, A., Shukla, S., Fallah, A., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive treatment that can provide partial and temporary relief from severe chronic pain, particularly in conditions like neuropathic pain and fibromyalgia.

While rTMS effects are generally short-lived, daily sessions over several weeks can lead to longer-lasting pain relief, and for patients who respond but later relapse, surgical options like implanted electrodes may help maintain the benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of repetitive transcranial magnetic stimulation in pain relief. Lefaucheur, JP.[2022]

In a study of 61 active-duty service members with treatment-resistant depression who underwent at least 20 sessions of repetitive transcranial magnetic stimulation (rTMS), there was a statistically significant reduction in depressive symptoms, as indicated by a decrease in average PHQ-9 scores from 15.8 to 12.6 (P < 0.001).

Approximately 69% of participants experienced a reduction in their depressive ratings, with 20% achieving a level of improvement that placed them in the nondysfunctional range, suggesting that rTMS is a promising treatment option for major depression in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression in Active-Duty Service Members Improves Depressive Symptoms. Roach, AE., Hines, C., Stafford, J., et al.[2022]

In a case study of one Vietnam veteran with chronic PTSD, 20 minutes of repetitive transcranial magnetic stimulation (rTMS) at 1 Hz to the right prefrontal area significantly reduced the exaggerated P3a response to combat-related images, indicating a potential therapeutic effect.

The study provides electrophysiological evidence supporting the effectiveness of right frontal rTMS in alleviating hyperarousability to trauma-related stimuli, aligning with the patient's subjective reports of symptom improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation and threat memory: selective reduction of combat threat memory p300 response after right frontal-lobe stimulation. Tillman, GD., Kimbrell, TA., Calley, CS., et al.[2012]

Repetitive transcranial magnetic stimulation (rTMS) is generally safe for older adults with late-life depression, with only 12.4% reporting any adverse events and serious adverse events occurring in just 1.5% of cases, based on a review of 11 studies involving 353 patients.

The most common adverse events were mild, such as headaches (6.9%) and discomfort at the stimulation site (2.7%), although some serious adverse events, including psychiatric hospitalization and increased suicidal ideation, were noted in case reports, highlighting the need for further research to ensure safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. Overvliet, GM., Jansen, RAC., van Balkom, AJLM., et al.[2021]

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 study involving 9 normal volunteers, rapid-rate transcranial magnetic stimulation (rTMS) was found to be generally safe, but it caused temporary hearing threshold shifts in 3 subjects and a seizure in one subject at the highest intensity, indicating a potential risk for seizures.

The study also demonstrated that rTMS can increase cortical excitability in contralateral muscles, with the extent of this effect varying based on the intensity and frequency of the stimulation, suggesting a need for careful monitoring and guidelines to mitigate side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of rapid-rate transcranial magnetic stimulation in normal volunteers. Pascual-Leone, A., Houser, CM., Reese, K., et al.[2019]

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]

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]

This trial will evaluate whether a 1-week accelerated rTMS treatment is as effective as the standard 4-week treatment for depression, involving 60 patients over a 2-year period.

The study aims to determine if additional accelerated rTMS treatments can benefit patients who do not respond to initial therapy, potentially optimizing treatment strategies for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated transcranial magnetic stimulation (aTMS) to treat depression with treatment switching: study protocol of a pilot, randomized, delayed-start trial. Tan, XW., Abdin, E., Tor, PC.[2021]

In a study involving 62 patients with treatment-resistant depression, rTMS showed a response rate of 29.4% and a remission rate of 5.9% over 6 weeks, indicating its potential effectiveness in clinical practice.

The study found that early life stress may predict a better response to rTMS therapy, although the overall remission rates were lower compared to other recent studies, suggesting the need for further research to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A naturalistic, multi-site study of repetitive transcranial magnetic stimulation therapy for depression. Taylor, SF., Bhati, MT., Dubin, MJ., et al.[2019]

In a study of 16 stroke patients, low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) applied to the contralesional hemisphere showed a trend towards rebalancing cortical excitability between the affected and unaffected sides over 90 days, suggesting potential benefits for motor recovery.

At 45 days post-stroke, patients receiving real rTMS demonstrated better upper limb motor function recovery compared to the sham group, although this difference was not significant by 90 days, indicating that while rTMS may aid in early recovery, its long-term efficacy may require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-frequency rTMS in patients with subacute ischemic stroke: clinical evaluation of short and long-term outcomes and neurophysiological assessment of cortical excitability. Blesneag, AV., Slăvoacă, DF., Popa, L., et al.[2018]

Repetitive magnetic stimulation (rTMS) is a non-invasive and painless technique that can effectively activate specific areas of the brain, making it useful for studying language, memory, and visual perception.

rTMS shows potential therapeutic benefits for conditions like movement disorders and depression, but there are safety considerations regarding its potential to induce seizures, which are addressed in the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation. Possibilities, limits and safety aspects]. Brandt, SA., Ploner, CJ., Meyer, BU.[2019]

References

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

Use of Repetitive Transcranial Magnetic Stimulation in the Treatment of Neuropsychiatric and Neurocognitive Symptoms Associated With Concussion in Military Populations. [2022]

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

Repetitive Transcranial Magnetic Stimulation in Managing Mild Traumatic Brain Injury-Related Headaches. [2022]

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

Use of repetitive transcranial magnetic stimulation in pain relief. [2022]

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

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression in Active-Duty Service Members Improves Depressive Symptoms. [2022]

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

Repetitive transcranial magnetic stimulation and threat memory: selective reduction of combat threat memory p300 response after right frontal-lobe stimulation. [2012]

6. England pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. [2021]

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

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

8. Ireland pubmed.ncbi.nlm.nih.gov

Safety of rapid-rate transcranial magnetic stimulation in normal volunteers. [2019]

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

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

10. 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]

11. England pubmed.ncbi.nlm.nih.gov

Accelerated transcranial magnetic stimulation (aTMS) to treat depression with treatment switching: study protocol of a pilot, randomized, delayed-start trial. [2021]

12. Netherlands pubmed.ncbi.nlm.nih.gov

A naturalistic, multi-site study of repetitive transcranial magnetic stimulation therapy for depression. [2019]

13. Romania pubmed.ncbi.nlm.nih.gov

Low-frequency rTMS in patients with subacute ischemic stroke: clinical evaluation of short and long-term outcomes and neurophysiological assessment of cortical excitability. [2018]

14. Germany pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation. Possibilities, limits and safety aspects]. [2019]