rTMS for Gulf War Syndrome

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether repetitive transcranial magnetic stimulation (rTMS) can reduce pain and other symptoms in people with Gulf War Illness. Participants are divided into groups: some receive real rTMS targeting specific brain areas, while others receive a sham version that mimics the process without delivering actual treatment. The trial is suitable for veterans of the Persian Gulf War who experience regular muscle or joint pain, weekly headaches, and some depression symptoms. As an unphased trial, it offers veterans the chance to contribute to groundbreaking research that could lead to new treatments for 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.

What prior data suggests that rTMS is safe for treating Gulf War Syndrome?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is generally safe. Past studies have used rTMS to treat conditions like chronic pain and depression. These studies indicate that while there is a very small risk of seizures, rTMS does not cause common side effects like weight gain.

Most people who have tried rTMS handle it well, with no reports of serious problems. This suggests that most people do not experience severe issues with this treatment. Therefore, evidence suggests that rTMS is a safe option for managing symptoms related to Gulf War Illness, such as pain and headaches. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using repetitive Transcranial Magnetic Stimulation (rTMS) for Gulf War Syndrome because it offers a non-invasive approach that directly targets brain activity. Traditional treatments often rely on medications like analgesics, antidepressants, or cognitive therapies, which can involve a range of side effects and may not address the neurological aspects of the condition. rTMS works by using magnetic fields to stimulate nerve cells in specific brain regions, such as the left dorsolateral prefrontal cortex (LDLPFC) and the left motor cortex (LMC), which could lead to improved symptoms without the need for medication. This method not only provides a new way to potentially alleviate symptoms but also expands our understanding of how brain stimulation can be used for complex conditions like Gulf War Syndrome.

What evidence suggests that rTMS might be an effective treatment for Gulf War Syndrome?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can help treat symptoms of Gulf War Illness. One study found that rTMS relieved chronic headaches, a common issue among affected veterans. Other research indicates that rTMS can also reduce pain and related symptoms such as fatigue and cognitive difficulties. This trial will compare different applications of rTMS, including active rTMS at the left dorsolateral prefrontal cortex (LDLPFC) and the left motor cortex (LMC), with sham rTMS at these same areas. Early findings suggest that targeting specific brain areas, like those involved in decision-making and movement on the left side, can improve symptoms for those with Gulf War Illness. ^{2 5 6 7 8}

Who Is on the Research Team?

Albert Yick Leung, MD

Principal Investigator

VA San Diego Healthcare System, San Diego, CA

Are You a Good Fit for This Trial?

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)

International Headache Society Criteria for Migraine Headache without aura

Exclusion Criteria

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

I suffer from chronic tension or cluster headaches.

Pending litigation

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Sham rTMS at the LMC Experimental Treatment 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.

Group II: Active rTMS at the LMC Experimental Treatment 1 Intervention

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

Group III: 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 IV: 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.

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04182659

Long Term Efficacy of Neuronavigation Guided rTMS in ... This study aims to look at the long term efficacy of using repetitive transcranial magnetic stimulation (rTMS) in relieving Gulf War Illness related headaches ...

2. withpower.com withpower.com/trial/rtms-for-gulf-war-syndrome-3da57

rTMS for Gulf War Syndrome · Info for Participants 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 ...

3. brainstimjrnl.com brainstimjrnl.com/article/S1935-861X(18)30235-3/fulltext

An exploratory fMRI study: rTMS in Gulf War Veterans with ... Recent studies support the use of rTMS as a promising non-invasive approach for treating chronic headache symptoms. As such, a select population of Gulf War ...

4. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT04046536

rTMS in Alleviating Pain and Co-Morbid Symptoms in Gulf ... 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 ...

5. nature.com nature.com/articles/s41598-020-75006-8

Diminished corticomotor excitability in Gulf War Illness ... Veterans with GWI related diffuse body pain demonstrated a state of diminished corticomotor excitability, suggesting a maladaptive supraspinal pain modulatory ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01608321

rTMS for the Treatment of Chronic Pain in GW1 Veterans This study was designed to evaluate the effect of repetitive Transcranial Magnetic Stimulation (rTMS) in the resolution of Chronic Pain.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0165032721011022

Prefrontal transcranial magnetic stimulation for depression ... Although there is a rare risk of seizure during stimulation, TMS has a favorable safety profile without systemic side effects (weight gain, ...

8. va.gov va.gov/RAC-GWVI/RTMSVA.pdf

Project Information - NIH REPORTER DESCRIPTION (provided by applicanty: This project will study 206 veterans with Gulf War Illness (GWI) whose symptoms include Chronic pain.