rTMS in Alleviating Pain and Co-Morbid Symptoms in Gulf War Veterans Illness (GWVI)

Study Overview
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Brief Summary
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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.

Detailed Description
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Headaches (HA), muscle and joint pain, are some of the most common debilitating symptoms in military personnel served in the 1990-1991 Persian Gulf War (GW1). Migraine like HA and diffuse body pain were detected in 64% of Gulf War Veteran (GWV) diagnosed with Gulf War Illness (GWI). Likewise, depression carries a very high co-morbid rate (50%) in patients with chronic pain, and in GWV with GWI related chronic HA and body muscle and joint pain conditions (GWI-HAP). Unfortunately, conventional pharmacological treatments for GWI-related pain has not been shown to be effective and drugs such as narcotics contain many long term untoward psychosomatic and abusive side effects. This study is assessing the effectiveness of repetitive transcranial magnetic stimulation (rTMS), non-invasive treatment option, in alleviating pain and other co-morbid symptoms of GWI.

Official Title
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rTMS in Alleviating Pain and Co-morbid Symptoms in GWVI

Conditions
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Gulf War Illness, Depression

Intervention / Treatment
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* Device: Transcranial Magnetic Stimulation
* Device: Sham Transcranial Magnetic Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female under 65 years of age who served in the military for at least 30 consecutive days between August 1, 1990, and July 31, 1991 in the Persian Gulf War region CDC Criteria for GWVI (GWI) Kansas Criteria for GWVI (GWI) International Headache Society Criteria for Migraine Headache without aura Average Overall Daily Muscle Pain Intensity >3 on 0-10 a NPS Average Overall Daily Extremities Joint Pain Intensity >3 on 0-10 a NPS Headache Exacerbation/attack once a week with the average intensity >3 on a 0-10 NPS, lasting > 1 hour in the past three months Hamilton Rating Scale of Depression (HRSD) greater than or equal to 14 based on the sum of scores for the first 17 items Exclusion Criteria: Pregnancy History of pacemaker implant Any ferromagnetic (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 History of seizure Pending litigation Low back pain with mechanical origins such as lumbar radiculopathy or radiculitis or lumbar facet arthropathy Lack of ability to understand the experimental protocol and to adequately communicate in English History of Traumatic Brain injury Chronic Tension or Cluster Headache Ongoing Cognitive Rehabilitation or Treatment of PTSD

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: There will be two groups: one will receive active rTMS and the other group will receive sham rTMS.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active rTMS at the LDLPFC<br>Subjects will receive the repetitive Transcranial Magnetic Stimulation (rTMS) study procedure at the left dorsolateral prefrontal cortex (LDLPFC). | Device: Transcranial Magnetic Stimulation<br>* A non-invasive treatment that emits magnetic pulses to stimulate the brain.<br>|
| Sham Comparator: Sham rTMS at the LDLPFC<br>Sham rTMS will appear the same as the active, with the same parameters, but will not receive the actual magnetic stimulation to the LDLPFC. | Device: Sham Transcranial Magnetic Stimulation<br>* Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation due to the use of a double sided Active/Sham coil used specifically for research studies.<br>|
| Active Comparator: Active rTMS at the LMC<br>Subjects will receive the repetitive Transcranial Magnetic Stimulation (rTMS) study procedure at the left motor cortex (LMC) | Device: Transcranial Magnetic Stimulation<br>* A non-invasive treatment that emits magnetic pulses to stimulate the brain.<br>|
| Sham Comparator: Sham rTMS at the LMC<br>Sham rTMS will appear the same as the active, with the same parameters, but will not receive the actual magnetic stimulation to the LMC. | Device: Sham Transcranial Magnetic Stimulation<br>* Sham rTMS will consist of the same parameters as active, however, the subject will not receive the actual magnetic stimulation due to the use of a double sided Active/Sham coil used specifically for research studies.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to post treatment of GWI-related pain and headaches | This outcome will be measured through daily self-reporting logs that tracks headache, muscle, and joint pain. A numerical rating scale of 0, being no pain, to 10, being worst possible pain, will be used to report pain and headaches. | Baseline, 1-week, 1-month, 2-month, and 3-month | 
| Change from baseline to post treatment of sensory and affective aspects of pain | Short Form McGill Pain Questionnaire (SF-MPQ): This is a self-report questionnaire that allows individuals to describe the quality and intensity of pain they are experiencing. This will be used to assess the sensory and affective aspects of muscle and joint pain. | Baseline, 1-week, 1-month, 2-month, and 3-month | 
| Change from baseline to post treatment of headaches | The Headache Impact Test (HIT-6) will be used to measure how headaches affect the individual's ability to function in different domains. This 6-question form assesses the severity of headache pain and is scored with a range of 36-78, with higher scores indicating a larger impact of headaches on functionality. | Baseline, 1-week, 1-month, 2-month, and 3-month | 
| Change from baseline to post treatment of depression | The Hamilton Rating Scale for Depression (HRSD) questionnaire will be used to assess depression, which consists of 21 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. | Baseline, 1-week, 1-month, 2-month, and 3-month | 
| Change from baseline to post treatment of quality of life | The Short Form Health Survey-36 (SF-36) is a self-reported survey of patient health. It is a measure of health status and quality of life in regards to eight main areas: vitality, physical functioning, bodily pain, health perceptions, physical, emotional, and social role functioning and mental health. | Baseline, 1-week, 1-month, 2-month, and 3-month | 
| Change from baseline to post treatment of body pain | A Brief Pain Inventory-Short Form (BPI-SF) questionnaire will also be used to assess the severity of pain and the impact of pain on daily functions. 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). | Baseline, 1-week, 1-month, 2-month, and 3-month | 
| Change from baseline to post treatment of muscle pain | The New Clinical Fibromyalgia Diagnostic Criteria - Part 1 will be used to assess muscle pain. Patients will be asked to rate the average (over the past 24 hours) intensity of muscle pain for up to 12 locations of the body. | Baseline, 1-week, 1-month, 2-month, and 3-month | 
| Change from baseline to post treatment of fibromyalgia | A Revised Fibromyalgia Impact Questionnaire will be used to evaluate the function, overall impact and symptoms of Fibromyalgia. There are a total of 21 questions, each with a range of 0-10, with 10 being either very difficult or always. | Baseline, 1-week, 1-month, 2-month, and 3-month | 
| Change from baseline to post treatment of neurobehavioral symptoms | The Neurobehavioral Symptoms Inventory (NSI) is a self-report questionnaire on the severity of various behavioral symptoms and is measured using a 5-item scale. It asks the subjects to indicate the extent to which each symptom has disturbed them. | Baseline, 1-week, 1-month, 2-month, and 3-month | 
| Change from baseline to post treatment of sleep quality | The Pittsburgh Sleep Quality Index (PSQI) questionnaire has nineteen individual items which are used to generate seven composite scores on: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Questions are either free-response or have a range from 0-3, with 3 being more frequent or very bad. | Baseline, 1-week, 1-month, 2-month, and 3-month | 
| Change from baseline to post treatment of sleep difficulties | The Insomnia Severity Index measures the severity of an individual's sleep difficulties. All questions range from 0-4 and the sum of the answers would give the total score. The total score range from 0-28. | Baseline, 1-week, 1-month, 2-month, and 3-month | 
| Change from baseline to post treatment of fatigue | The Flinders Fatigue Scale measures daytime fatigue associated with insomnia through a 7-item questionnaire. The questions range from 1-5, with 5 being extremely or entirely. | Baseline, 1-week, 1-month, 2-month, and 3-month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to post treatment of PTSD symptoms | The Clinician-Administered PTSD Scale (CAPS-5), 30-item structured interview that can be used to diagnose PTSD and associated symptoms, will be used to assess PTSD symptoms | Baseline, 1-week, 1-month, 2-month, and 3-month | 
| Change in opioid-based pain medication usage | Medication assessment consists of daily chronic and breakthrough opioid usage for pain or headache. Average daily dosage will be converted to equal-potent oral Morphine Sulfate dosage based on the clinical opioid conversion table used by the VASDHS Pain Service and University of California, San Diego, Center for Pain Medicine. The study participants will be asked to remain on the same analgesic medication(s) during the study period but are allowed to titrate down their narcotic usage. | Baseline, 1-week, 1-month, 2-month, and 3-month | 
| Explore changes in supraspinal resting state functional connectivity | The outcome measure will be assessed through functional magnetic imaging scans and subsequent processing. | Baseline and 1-week post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rTMS, Transcranial Magnetic Stimulation, Gulf War Illness, Depression