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

Veterans Medical Research Foundation140 enrolled

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.

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.

Study Type

INTERVENTIONAL

Interventions

Active Repetitive Transcranial Magnetic StimulationDEVICE

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

Active Repetitive Transcranial Magnetic StimulationDEVICE

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

Active Repetitive Transcranial Magnetic StimulationDEVICE

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

Active Repetitive Transcranial Magnetic StimulationDEVICE

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Pain Intensity - Mechanical Visual Analogue Scale (M-VAS)

A scale that ranges from 0 to 10 ("No pain" to "Worst possible pain").

Time frame: From baseline to the end of treatment at 16 weeks

Headache and Pain Log

A personal daily log is used to track the subject's headaches, muscle and joint pain throughout the course of the study based on a range of 0 to 10, with higher scores indicating more severe pain.

Time frame: From enrollment to the end of treatment at 16 weeks

Mood - Hamilton Rating Scale for Depression (HRSD)

This scale is a well-established questionnaire which consists of twenty-one questions and rates the severity of symptoms observed in depression such as low mood, insomnia, agitation, anxiety and weight loss. Only the first 17 items are used for the overall scoring. A score between 14 and 18 represents a moderate form of depression and a score greater than 19 represents severe depression.

Time frame: From baseline to end of treatment at 16 weeks

Pain Severity - Brief Pain Inventory-Short Form (BPI-sf)

This is a self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during the 24-hour period prior to evaluation. The BPI-sf consists of five questions. Four items measure pain on 11-point response scales from 0 to 10 ("No Pain" to "Pain as bad as you can imagine"). Another item, containing 7 sub-questions, evaluates the level of pain interference with daily functioning on 11-point response scales from 0 to 10 ("Does not interfere" to "Completely interferes"). Items 3-6 are summed together for a total average pain severity score.