Recruiting

rTMS

Sponsor:

Veterans Medical Research Foundation

Code:

NCT07325513

Conditions

Gulf War Illness

Headache

Muscle and Joint Pain

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

Active Repetitive Transcranial Magnetic Stimulation

Active Repetitive Transcranial Magnetic Stimulation

Active Repetitive Transcranial Magnetic Stimulation

Active Repetitive Transcranial Magnetic Stimulation

Study Details

Brief summary:

The goal of this clinical trial is to create a machine learning algorithm to improve active repetitive transcranial magnetic stimulation (rTMS) treatments for veterans and/or active military personnel by alleviating Gulf War Illness related headaches and body pain (GWI-HAP). This study aims to develop and validate a Support Vector Machine (SVM) model that could replace the trial-and-error process by assessing functional connectivity provided by resting state functional magnetic resonance imaging (rs-fMRI) data to predict the most effective rTMS protocol for each person. All participants will be receiving active rTMS treatment.

The main questions it intends to answer are:

1. Does the SVM model predict a more effective treatment response rate for predicted respondents undergoing active rTMS at the left dorsolateral prefrontal cortex (DLPFC) compared to predicted non-respondents?
2. Does the SVM model predict a more effective treatment response rate while undergoing active rTMS at the left dorsolateral prefrontal cortex (DLPFC) and left motor cortex (LMC) in predicted respondents compared to predicted non-respondents?

Participants will undergo the following:

1. Receive a total of 13 active rTMS treatment sessions over 3-4 months.
2. Visit the clinic for a total of 15 visits for assessments, check ups, and treatments.
3. Keep a daily log of their headaches, muscle and joint pain throughout the study.

Conditions

Gulf War Illness

Headache

Muscle and Joint Pain

Study ID

NCT07325513

Start date

Mar 25, 2026

Status verified date

Dec, 2025

Completion date

Oct, 2029

Anticipated

Primary completion date

Oct, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Male or female
  • Veteran or active military personnel
  • Between the ages of 18 and 65 years old
  • Served in the Persian Gulf region for at least 30 consecutive days between August 1, 1990, and July 31, 1991
  • Meets the CDC Criteria for GWVI (GWI), with symptoms starting during or after the 1990-1991 Persian Gulf deployment. Symptoms must be present for at least 6 months prior to enrollment in the study. Symptoms must be present in at least 2 of the 3 categories of fatigue, musculoskeletal, and mood cognitive.
  • Meets the Kansas Criteria for GWVI (GWI), with symptoms starting during or after the 1990-1991 Persian Gulf deployment. Symptoms must be present for at least 6 months prior to enrollment in the study. Qualifying symptoms must be at least moderate in severity and/or multiple symptoms must be present within at least 3 of 6 categories consisting of fatigue/sleep, neurological/cognitive/mood, pain, respiratory, gastroenterological, and dermatological symptomology.
  • Average Overall Daily Muscle Pain Intensity ≥3 on a 0-10 NPRS, present for at least 6 months
  • Average Overall Daily Extremities Joint Pain Intensity ≥3 on a 0-10 NPRS, present for at least 6 months
  • Average Headache Exacerbation Intensity ≥3 on a 0-10 NPRS, with headaches occurring for at least 6 months
  • Headache Exacerbation/attack ≥ 1 time per week with the average intensity ≥3 on a 0-10 NPS, lasting > 1 hour in the past three months
  • International Headache Society Criteria for Migraine Headache without aura

Exclusion Criteria:

  • Children under the age of 18
  • Pregnant women
  • Individuals with cognitive/decisional impairment
  • Non-English speaking individuals
  • Prisoners of War
  • Incarcerated individuals
  • VA employees - including VA paid, IPA, or WOC
  • Students of the institution or of the investigator
  • Patients with cancer
  • History of pacemaker implant
  • Presence of ferromagnetic material (e.g., bullet fragment, shrapnel, device implant) in the brain or body that will prohibit the patients from having a brain MRI
  • History of dementia, major psychiatric diseases, or life-threatening diseases
  • Presence of any other chronic neuropathic pain states such as Complex Regional Pain Syndrome or Painful Peripheral Neuropathy
  • Known diagnosis of moderate to severe osteoarthritis and/or rheumatologic joint pain prior to the GWI deployment
  • Low back pain with mechanical origins such as lumbar radiculopathy or radiculitis or lumbar facet arthropathy
  • Concurrent conditions, like lupus, that can produce symptoms compatible with GWVI
  • History of seizure
  • Pending litigation
  • History of Traumatic Brain Injury-related headaches
  • Chronic Tension or Cluster Headache. However, subjects with occasional tension headaches (less than once every three months and lasting no more than 24 hours) will not be excluded from the study.
  • Ongoing Cognitive Rehabilitation or Treatment of PTSD
  • Recent exacerbation of anxiety disorder symptoms, active substance dependence, and/or current psychotic symptoms
  • Ongoing suicidal/homicidal ideation or recent (in the past 6 months) suicidal attempts
  • Patients who receive any narcotic-based analgesic, topical analgesics over the affected site, steroid and local anesthetic injection, anticonvulsants, and antipsychotic medications less than 7 days prior to the pretreatment assessment
  • Patients who do not agree to avoid use of non-pharmacologic treatments, including but not limited to, transcutaneous electrical nerve stimulation unit (TENS), acupuncture, acupressure, and therapeutic massage during the entire study.
  • Patients who do not agree to use additional acetaminophen (up to a maximum total of 3g per day) as the only rescue medication
  • Patients who have received rTMS within the past 6 months

Study Design

Enrollment

140 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Group A: Predicted Respondent at LDLPFC

active comparator: Group B: Predicted Non-respondent at LDLPFC

active comparator: Group C: Predicted Respondent at LDLPFC and LMC

active comparator: Group D: Predicted Non-respondent at LDLPFC and LMC

Interventions

Active Repetitive Transcranial Magnetic Stimulation

rTMS will be administered to the LDLPFC with an active coil.

Active Repetitive Transcranial Magnetic Stimulation

rTMS will be administered to the LDLPFC with an active coil.

Active Repetitive Transcranial Magnetic Stimulation

rTMS will be administered to the LDLPFC and LMC with an active coil.

Active Repetitive Transcranial Magnetic Stimulation

rTMS will be administered to the LDLPFC and LMC with an active coil.

Primary outcome measure

  • Pain Intensity - Mechanical Visual Analogue Scale (M-VAS) [ Time Frame: From baseline to the end of treatment at 16 weeks ]
  • Headache and Pain Log [ Time Frame: From enrollment to the end of treatment at 16 weeks ]
  • Mood - Hamilton Rating Scale for Depression (HRSD) [ Time Frame: From baseline to end of treatment at 16 weeks ]
  • Pain Severity - Brief Pain Inventory-Short Form (BPI-sf) [ Time Frame: Baseline, 1-week, 1-month, 2-months ]
  • Pain Severity - Brief Pain Inventory-Short Form (BPI-sf) [ Time Frame: Baseline, 1-week, 1-month, 2-months ]
  • Pain Quality and Intensity - Short Form McGill Pain Questionnaire (SF-MPQ) [ Time Frame: Baseline, 1-week, 1-month, 2-months ]
  • Pain Quality and Intensity - Short Form McGill Pain Questionnaire (SF-MPQ) [ Time Frame: Baseline, 1-week, 1-month, 2-months ]
  • Functionality - Revised Fibromyalgia Impact Questionnaire [ Time Frame: Baseline, 1-week, 1-month, 2-months ]
  • Pain Intensity - New Clinical Fibromyalgia Diagnostic Criteria - Part 1 [ Time Frame: Baseline, 1-week, 1-month, 2-months ]
  • Pain Severity - Headache Impact Test (HIT-6) [ Time Frame: Baseline, 1-week, 1-month, 2-months ]
  • Pain Severity - Neurobehavioral Symptoms Inventory (NSI) [ Time Frame: Baseline, 1-week, 1-month, 2-months ]
  • Sleep Quality - Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: Baseline, 1-week, 1-month, 2-months ]
  • Sleep Severity - Insomnia Severity Index [ Time Frame: Baseline, 1-week, 1-month, 2-months ]
  • Quality of Life - Veteran RAND 36-item Health Survey (VR-36+PCS and MCS) [ Time Frame: Baseline, 1-week, 1-month, 2-months ]
  • Multidimensional Fatigue Inventory [ Time Frame: Baseline, 1-week, 1-month, 2-months ]
  • Chronic Fatigue Severity Scale [ Time Frame: Baseline, 1-week, 1-month, 2-months ]

Central Contacts and Locations

Central contacts

Albert Y Leung, MD

8585528585ayleung@health.ucsd.edu

Caleb Lopez, BS

8585528585caleb.lopez@va.gov

Locations

Jennifer Moreno Department of Veterans Affairs Medical Center

Recruiting

San Diego, California, United States, 92161

Contacts

Caleb Lopez, B.S.

8585528585caleb.lopez@va.gov

Principal Investigator:

Albert Leung, M.D.

More Information

Sponsor

Veterans Medical Research Foundation

Last update posted

Apr 13, 2026

Last verified

Dec, 2025

Keywords

  • Repetitive Transcranial Magnetic Stimulation (rTMS)
  • Support Vector Machine (SVM)
  • Headache
  • Machine Learning
  • Muscle and Joint Pain

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Veterans Medical Research Foundation on 2026-04-13.