Clinical trial NCT03030794: Alleviating Headache and Pain in GWI With Neuronavigation Guided rTMS
Official title: Alleviating Headache and Pain in GWI With Neuronavigation Guided rTMS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gulf War Syndrome
Headache
Keywords: Gulf War Illness
Headache
Muscle Pain
Joint Pain
TMS
Lead sponsor: Veterans Medical Research Foundation
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2017-01-25
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to assess the effect of repetitive transcranial magnetic stimulation (rTMS) on Gulf War illness related headaches and pain.

Detailed description: Headaches (HA) and wide spread pain are some of the most common debilitating symptoms in Gulf War Veterans (GWV) with Gulf War Illness (GWI). Migraine like HA and diffuse body pain were detected in 64% of GWV with GWI. This high prevalence of chronic HA and diffuse body pain conditions are often associated with neuropsychological dysfunction in mood, attention, memory and other systemic symptoms, which cast a profound negative impact on patients' quality of life. Unfortunately, conventional pharmacological treatments for GWI related headaches and pain (GWI-HAP) has not been shown to be effective and drugs such as narcotics contain many long term untoward psychosomatic and abusive side effects. Therefore, developing and validating non-invasive and low risk innovative treatment for this patient population is warranted. Transcranial Magnetic Stimulation (TMS) is currently a US FDA approved treatment for major depression and migraine HA.

Eligibility criteria: Criteria for veterans with Gulf War Illness headaches and pain:

Inclusion Criteria:

* Male or female between ages 18-65
* CDC Criteria for GWI
* Kansas Criteria for GWI
* International Headache Society Criteria for Migraine HA w/o aura
* Average Headache Exacerbation Intensity \>3 on 0-10 NPRS
* Average Overall Daily Muscle Pain Intensity \>3 on 0-10 NPRS
* Average Overall Daily Extremities Joint Pain Intensity \>3 on 0-10 NPRS
* Headache Exacerbation/Attack ≥ 3 times/week, lasting \>4 hrs in past 3 months

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

Criteria for healthy veterans without Gulf War Illness headaches and pain:

Inclusion Criteria:

* Male or female between ages 18-65
* Served at least 30 consecutive days in the Persian Gulf between 8/90-7/91

Exclusion Criteria:

* CDC Criteria for GWI
* Kansas Criteria for GWI
* International Headache Society Criteria for Migraine HA w/o aura
* Average Headache Exacerbation Intensity \>3 on 0-10 NPRS
* Average Overall Daily Muscle Pain Intensity \>3 on 0-10 NPRS
* Average Overall Daily Extremities Joint Pain Intensity \>3 on 0-10 NPRS
* Headache Exacerbation/Attack ≥ 3 times/week, lasting \>4 hrs in past 3 months
* 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

Primary outcomes:
measure: Daily Headache and Pain Log
timeFrame: 2 months for each subject (11 visits)
measure: Headache Impact Test 6 (HIT-6)
timeFrame: 2 months for each subject (11 visits)
measure: 2 months for each subject (11 visits)
timeFrame: 2 months for each subject (11 visits)
measure: Opioid Medication Assessment
timeFrame: 2 months for each subject (11 visits)
measure: Mechanical-Visual Analogue Scale
timeFrame: 2 months for each subject (11 visits)
Secondary outcomes:
measure: Neurobehavioral Symptom Inventory (NSI)
timeFrame: 2 months for each subject (11 visits)
measure: Short-Form McGill Pain Questionnaire (SF-MPQ)
timeFrame: 2 months for each subject (11 visits)
measure: New Clinical Fibromyalgia Diagnostic Criteria
timeFrame: 2 months for each subject (11 visits)
measure: Revised Fibromyalgia Impact Questionnaire (FIQR)
timeFrame: 2 months for each subject (11 visits)
measure: Conners Continuous Performance Test 2 (CPT2)
timeFrame: 2 months for each subject (11 visits)
measure: Hopkins Verbal Learning Test (HVLT)
timeFrame: 2 months for each subject (11 visits)
measure: Trailmaking Test A&B
timeFrame: 2 months for each subject (11 visits)
measure: This is a timed test that is administered to assess executive function. Both tests have a series of numbers or numbers and letters that are to be connected in sequential order. The faster the completion time, the better the executive function.
timeFrame: 2 months for each subject (11 visits)
measure: Hamilton Rating Scale for Depression
timeFrame: 2 months for each subject (11 visits)
measure: 36-Item Short Form Survey Instrument (SF-36)
timeFrame: 2 months for each subject (11 visits)
measure: Sleep Quality Assessment (PSQI)
timeFrame: 2 months for each subject (11 visits)
measure: Insomnia Severity Index
timeFrame: 2 months for each subject (11 visits)
measure: Flinders Fatigue Scale
timeFrame: 2 months for each subject (11 visits)
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Naval Medical Center San Diego
state: California
city: San Diego
country: United States
facility: Veteran Affairs Hospital
state: California
Study officials:
affiliation: VA San Diego Health Care System
name: Albert Leung, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leung A, Donohue M, Xu R, Lee R, Lefaucheur JP, Khedr EM, Saitoh Y, Andre-Obadia N, Rollnik J, Wallace M, Chen R. rTMS for suppressing neuropathic pain: a meta-analysis. J Pain. 2009 Dec;10(12):1205-16. doi: 10.1016/j.jpain.2009.03.010. Epub 2009 May 23.
citation: Leung A, Shukla S, Fallah A, Song D, Lin L, Golshan S, Tsai A, Jak A, Polston G, Lee R. Repetitive Transcranial Magnetic Stimulation in Managing Mild Traumatic Brain Injury-Related Headaches. Neuromodulation. 2016 Feb;19(2):133-41. doi: 10.1111/ner.12364. Epub 2015 Nov 10.
citation: Lei K, Kunnel A, Metzger-Smith V, Golshan S, Javors J, Wei J, Lee R, Vaninetti M, Rutledge T, Leung A. Diminished corticomotor excitability in Gulf War Illness related chronic pain symptoms; evidence from TMS study. Sci Rep. 2020 Oct 28;10(1):18520. doi: 10.1038/s41598-020-75006-8.