Machine Learning in Guiding rTMS Treatment for GWI-Related Headaches and Body Pain

Overview

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.

Detailed description

This study aims to enroll a total of 140 veterans and/or active military personnel over the 4-year study period at the VA San Diego Healthcare System (VASDHS). Participants will be randomized into receiving treatments at the left DLPFC or left DLPFC and LMC, then placed into predicted respondent or non-respondent groups. They will be assigned to 1 of 4 groups:

Group A: Predicted Respondent at Left DLPFC Group B: Predicted Non-respondent at Left DLPFC Group C: Predicted Respondent at Left DLPFC and LMC Group D: Predicted Non-respondent at Left DLPFC and LMC

Participation in this study will require 15 total visits to the VASDHS over the course of 3-4 months. The visits will be separated in the following phases:

1. Pre-Treatment Assessments Phase (Weeks 1-2): Visit 1 (Screening) and Visit 2 (Baseline Assessments) 2. Induction Treatment Phase (Weeks 2-4): Visits 3-12 (Weekday active rTMS sessions at \>24 hours and \<72 hours apart) 3. Follow-Up and Maintenance Phase (Weeks 5-10): Visit 13 (1 week follow-up); Visit 14 (1 month follow-up); Visit 15 (2 months follow-up); All maintenance visits follow the final treatment of the induction phase.

Interventions

• Device Active Repetitive Transcranial Magnetic Stimulation
  rTMS will be administered to the LDLPFC with an active coil.
• Device Active Repetitive Transcranial Magnetic Stimulation
  rTMS will be administered to the LDLPFC with an active coil.
• Device Active Repetitive Transcranial Magnetic Stimulation
  rTMS will be administered to the LDLPFC and LMC with an active coil.
• Device Active Repetitive Transcranial Magnetic Stimulation
  rTMS will be administered to the LDLPFC and LMC with an active coil.

Primary outcome measures

• 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]

Secondary outcome measures (1)

• Opiate/Medication Assessment [Time frame: From the baseline to the end of treatment at 16 weeks]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Jennifer Moreno Department of Veterans Affairs Medical Center — San Diego

Identifiers

NCT: NCT07325513 · H2500180 · CDMRP-TX240370

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗