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Alleviating Headache and Pain in GWI With Neuronavigation Guided rTMS

Primary Purpose

Gulf War Syndrome, Headache

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Repetitive transcranial magnetic stimulation
Repetitive transcranial magnetic stimulation (sham)
Sponsored by
Veterans Medical Research Foundation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gulf War Syndrome focused on measuring Gulf War Illness, Headache, Muscle Pain, Joint Pain, TMS

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Naval Medical Center San Diego
  • Veteran Affairs Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Repetitive TMS

No (blocked) repetitive TMS

Arm Description

Subjects will receive the repetitive transcranial magnetic stimulation study procedure.

Subjects will not receive the repetitive transcranial magnetic stimulation study procedure by blocking the stimulation between the coil and the head, but the audiovisual conditions will be mimicked.

Outcomes

Primary Outcome Measures

Daily Headache and Pain Log
This is a daily self-reporting log that tracks headache, muscle pain, and joint pain levels. The pain levels are scored from 0-10 with 10 being the worst possible pain.
Headache Impact Test 6 (HIT-6)
This 6-question form assesses the severity of headache pain and is scored with a range of 36-78. The higher score, the higher the impact of headaches on functional ability.
2 months for each subject (11 visits)
This assessment has 9 questions about pain level, relief, and interference. Pain level and interference questions range from 0-10, with 10 being the worst. Level of relief has a range of 0-100%, with 100% being complete relief.
Opioid Medication Assessment
This is a self-reporting log that tracks opioid medication usage. Average daily dosages are converted to equal-potent oral Morphine Sulfate dosage and reported in milligrams.
Mechanical-Visual Analogue Scale
This scale measures the level of headache, muscle, and joint pain at each visit. This ranges from 0-100, with 100 being the worst possible pain.

Secondary Outcome Measures

Neurobehavioral Symptom Inventory (NSI)
This is a 22-question self-report assessment that tracks symptoms over time. Each question ranges from 0-4, with 4 being very severe. The total NSI score ranges from 0-88.
Short-Form McGill Pain Questionnaire (SF-MPQ)
This self-reporting survey contains 15 questions that describe the type of pain. Each descriptor is scored between 0-3, with 3 being severe pain. The total score then ranges from 0-45. This questionnaire is filled out one each for joint pain and one for muscle pain.
New Clinical Fibromyalgia Diagnostic Criteria
This form contains a checklist of 19 possible areas for muscle pain. The checkmarks are tallied to give the Widespread Pain Index score, which ranges from 0-19. A score of 19 would suggest muscle pain in all 19 possible locations.
Revised Fibromyalgia Impact Questionnaire (FIQR)
This 3-part questionnaire measures the level of interference the pain causes, the overall impact of the pain, and intensity of the symptoms. There are a total of 21 questions, each with a range of 0-10, with 10 being either "very difficult" or "always." The FIQR total has a range of 0-210.
Conners Continuous Performance Test 2 (CPT2)
This is a 15-minute attention task administered on a laptop. The subject is prompted to press the spacebar as quickly as possible after every letter that appears on the screen except for the letter X. The exam is automatically scored by the program and reports omission rate and response latency. The attentional cognitive function is tracked by their change in these scores over time.
Hopkins Verbal Learning Test (HVLT)
This is a memory and recall task that requires the subject to memorize a list of 10 words and recall them. There are 3 trials and they are scored just by the number of words that can be recalled each time, which can be from 0-10 for a total range of 0-30 words. The second part of this test rates their recognition discrimination index by asking if certain words were on the original list. This is scored by taking the number of true positives and subtracting the false positives. The range for this is from 0-12, with 12 indicative of better discrimination within memory.
Trailmaking Test A&B
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.
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.
This is an administered IQ test that is designed to measure intelligence and cognitive ability in adults and older adolescents. There are several parts to the test, with each response being scored from 0-2 or 0-4 based on the quality of the answer or the completion time. The raw scores are then converted to scaled scores and summed to give the Full Scale score. The higher the Full Scale score, the higher the IQ classification.
Hamilton Rating Scale for Depression
This questionnaire rates the severity of depression in 21 questions. Each question either ranges from 0-2 or 0-4. The sum of the scores would give the total score, where a higher score would mean more severe depression.
36-Item Short Form Survey Instrument (SF-36)
This is a 38-question survey that assesses physical function, physical health limitations, emotional problem limitations, fatigue, emotional well-being, social functioning, pain, and general health. The scoring follows the official guidelines by RAND, where certain questions determine each health aspect. The questions are rated from 1-5, and then scored from 0-100. Each health aspect will have a range of 0-100, with 100 suggesting a more favorable health state.
Sleep Quality Assessment (PSQI)
This is self-reporting survey has 9 questions and determines the quality and patterns of sleep. Questions are either free-response or have a range from 0-3, with 3 being "more frequent" or "very bad." The responses will be scored based on the guidelines at the bottom of the page. The global PSQI score then has a range of 0-21, with 21 indicative of poor sleep quality.
Insomnia Severity Index
This survey has 7 questions that rate the severity of insomnia problems. All questions range from 0-4 and the sum of the answers would give the total score. The total score range from 0-28, with 28 being severe clinical insomnia.
Flinders Fatigue Scale
This questionnaire contains 7 questions in order to determine the level of fatigue one is experiencing. The questions range from 1-5, with 5 being "extremely" or "entirely." The higher one scores, the more severe the fatigue.

Full Information

First Posted
January 4, 2017
Last Updated
January 13, 2020
Sponsor
Veterans Medical Research Foundation
Collaborators
United States Department of Defense
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1. Study Identification

Unique Protocol Identification Number
NCT03030794
Brief Title
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

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
December 2016 (undefined)
Primary Completion Date
June 2019 (Actual)
Study Completion Date
June 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Veterans Medical Research Foundation
Collaborators
United States Department of Defense

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gulf War Syndrome, Headache
Keywords
Gulf War Illness, Headache, Muscle Pain, Joint Pain, TMS

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
90 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Repetitive TMS
Arm Type
Active Comparator
Arm Description
Subjects will receive the repetitive transcranial magnetic stimulation study procedure.
Arm Title
No (blocked) repetitive TMS
Arm Type
Placebo Comparator
Arm Description
Subjects will not receive the repetitive transcranial magnetic stimulation study procedure by blocking the stimulation between the coil and the head, but the audiovisual conditions will be mimicked.
Intervention Type
Device
Intervention Name(s)
Repetitive transcranial magnetic stimulation
Intervention Description
A non-invasive method of brain stimulation that emits a magnetic pulse.
Intervention Type
Device
Intervention Name(s)
Repetitive transcranial magnetic stimulation (sham)
Intervention Description
No brain stimulation will be administered.
Primary Outcome Measure Information:
Title
Daily Headache and Pain Log
Description
This is a daily self-reporting log that tracks headache, muscle pain, and joint pain levels. The pain levels are scored from 0-10 with 10 being the worst possible pain.
Time Frame
2 months for each subject (11 visits)
Title
Headache Impact Test 6 (HIT-6)
Description
This 6-question form assesses the severity of headache pain and is scored with a range of 36-78. The higher score, the higher the impact of headaches on functional ability.
Time Frame
2 months for each subject (11 visits)
Title
2 months for each subject (11 visits)
Description
This assessment has 9 questions about pain level, relief, and interference. Pain level and interference questions range from 0-10, with 10 being the worst. Level of relief has a range of 0-100%, with 100% being complete relief.
Time Frame
2 months for each subject (11 visits)
Title
Opioid Medication Assessment
Description
This is a self-reporting log that tracks opioid medication usage. Average daily dosages are converted to equal-potent oral Morphine Sulfate dosage and reported in milligrams.
Time Frame
2 months for each subject (11 visits)
Title
Mechanical-Visual Analogue Scale
Description
This scale measures the level of headache, muscle, and joint pain at each visit. This ranges from 0-100, with 100 being the worst possible pain.
Time Frame
2 months for each subject (11 visits)
Secondary Outcome Measure Information:
Title
Neurobehavioral Symptom Inventory (NSI)
Description
This is a 22-question self-report assessment that tracks symptoms over time. Each question ranges from 0-4, with 4 being very severe. The total NSI score ranges from 0-88.
Time Frame
2 months for each subject (11 visits)
Title
Short-Form McGill Pain Questionnaire (SF-MPQ)
Description
This self-reporting survey contains 15 questions that describe the type of pain. Each descriptor is scored between 0-3, with 3 being severe pain. The total score then ranges from 0-45. This questionnaire is filled out one each for joint pain and one for muscle pain.
Time Frame
2 months for each subject (11 visits)
Title
New Clinical Fibromyalgia Diagnostic Criteria
Description
This form contains a checklist of 19 possible areas for muscle pain. The checkmarks are tallied to give the Widespread Pain Index score, which ranges from 0-19. A score of 19 would suggest muscle pain in all 19 possible locations.
Time Frame
2 months for each subject (11 visits)
Title
Revised Fibromyalgia Impact Questionnaire (FIQR)
Description
This 3-part questionnaire measures the level of interference the pain causes, the overall impact of the pain, and intensity of the symptoms. There are a total of 21 questions, each with a range of 0-10, with 10 being either "very difficult" or "always." The FIQR total has a range of 0-210.
Time Frame
2 months for each subject (11 visits)
Title
Conners Continuous Performance Test 2 (CPT2)
Description
This is a 15-minute attention task administered on a laptop. The subject is prompted to press the spacebar as quickly as possible after every letter that appears on the screen except for the letter X. The exam is automatically scored by the program and reports omission rate and response latency. The attentional cognitive function is tracked by their change in these scores over time.
Time Frame
2 months for each subject (11 visits)
Title
Hopkins Verbal Learning Test (HVLT)
Description
This is a memory and recall task that requires the subject to memorize a list of 10 words and recall them. There are 3 trials and they are scored just by the number of words that can be recalled each time, which can be from 0-10 for a total range of 0-30 words. The second part of this test rates their recognition discrimination index by asking if certain words were on the original list. This is scored by taking the number of true positives and subtracting the false positives. The range for this is from 0-12, with 12 indicative of better discrimination within memory.
Time Frame
2 months for each subject (11 visits)
Title
Trailmaking Test A&B
Description
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.
Time Frame
2 months for each subject (11 visits)
Title
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.
Description
This is an administered IQ test that is designed to measure intelligence and cognitive ability in adults and older adolescents. There are several parts to the test, with each response being scored from 0-2 or 0-4 based on the quality of the answer or the completion time. The raw scores are then converted to scaled scores and summed to give the Full Scale score. The higher the Full Scale score, the higher the IQ classification.
Time Frame
2 months for each subject (11 visits)
Title
Hamilton Rating Scale for Depression
Description
This questionnaire rates the severity of depression in 21 questions. Each question either ranges from 0-2 or 0-4. The sum of the scores would give the total score, where a higher score would mean more severe depression.
Time Frame
2 months for each subject (11 visits)
Title
36-Item Short Form Survey Instrument (SF-36)
Description
This is a 38-question survey that assesses physical function, physical health limitations, emotional problem limitations, fatigue, emotional well-being, social functioning, pain, and general health. The scoring follows the official guidelines by RAND, where certain questions determine each health aspect. The questions are rated from 1-5, and then scored from 0-100. Each health aspect will have a range of 0-100, with 100 suggesting a more favorable health state.
Time Frame
2 months for each subject (11 visits)
Title
Sleep Quality Assessment (PSQI)
Description
This is self-reporting survey has 9 questions and determines the quality and patterns of sleep. Questions are either free-response or have a range from 0-3, with 3 being "more frequent" or "very bad." The responses will be scored based on the guidelines at the bottom of the page. The global PSQI score then has a range of 0-21, with 21 indicative of poor sleep quality.
Time Frame
2 months for each subject (11 visits)
Title
Insomnia Severity Index
Description
This survey has 7 questions that rate the severity of insomnia problems. All questions range from 0-4 and the sum of the answers would give the total score. The total score range from 0-28, with 28 being severe clinical insomnia.
Time Frame
2 months for each subject (11 visits)
Title
Flinders Fatigue Scale
Description
This questionnaire contains 7 questions in order to determine the level of fatigue one is experiencing. The questions range from 1-5, with 5 being "extremely" or "entirely." The higher one scores, the more severe the fatigue.
Time Frame
2 months for each subject (11 visits)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Albert Leung, M.D.
Organizational Affiliation
VA San Diego Health Care System
Official's Role
Principal Investigator
Facility Information:
Facility Name
Naval Medical Center San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92134
Country
United States
Facility Name
Veteran Affairs Hospital
City
San Diego
State/Province
California
ZIP/Postal Code
92161
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
19464959
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.
Results Reference
background
PubMed Identifier
26555886
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.
Results Reference
background
PubMed Identifier
33116195
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.
Results Reference
derived

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Alleviating Headache and Pain in GWI With Neuronavigation Guided rTMS

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