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Long Term Efficacy of Neuronavigation Guided rTMS in Alleviating Gulf War Illness Related Headaches and Pain Symptoms

Primary Purpose

Gulf War Syndrome, Gulf War Illness, Headache

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Transcranial Magnetic Stimulation
Sham Transcranial Magnetic Stimulation
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 rTMS, Transcranial Magnetic Stimulation, Gulf War Illness

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
  • Center for Disease Control (CDC) Criteria for Gulf War Illness (GWI)
  • Kansas Criteria for GWI
  • International Headache Society Criteria for Migraine Headache without aura Average Headache Exacerbation Intensity >3 on 0-10 a Numerical Pain Rating scale (NPS)
  • 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 3 times per week with the average intensity >3 on a 0-10 NPS, lasting > 4 hours in the past three months
  • Hamilton Rating Scale of Depression (HRSD) <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

Sites / Locations

  • VA Palo AltoRecruiting
  • VA San Diego Healthcare SystemRecruiting
  • VA AtlantaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Active rTMS at the LMC

Sham rTMS at the LMC

Arm Description

Subjects will receive the repetitive Transcranial Magnetic Stimulation (rTMS) study procedure at the left motor cortex (LMC)

Sham rTMS will appear the same as the active, with the same parameters, but will not receive the actual magnetic stimulation to the LMC.

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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").
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.
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."
Change from baseline to post treatment of neurobehavioral symptoms
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."
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.
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."

Secondary Outcome Measures

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
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 VA San Diego Healthcare System 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.
Explore changes in supraspinal resting state functional connectivity
The outcome measure will be assessed through functional magnetic imaging scans and subsequent processing.

Full Information

First Posted
November 27, 2019
Last Updated
August 7, 2023
Sponsor
Veterans Medical Research Foundation
Collaborators
United States Department of Defense
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1. Study Identification

Unique Protocol Identification Number
NCT04182659
Brief Title
Long Term Efficacy of Neuronavigation Guided rTMS in Alleviating Gulf War Illness Related Headaches and Pain Symptoms
Official Title
Long Term Efficacy of Neuronavigation Guided rTMS in Alleviating Gulf War Illness Related Headaches and Pain Symptoms
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2019 (Actual)
Primary Completion Date
September 30, 2023 (Anticipated)
Study Completion Date
September 30, 2023 (Anticipated)

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

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study aims to look at the long term efficacy of using repetitive transcranial magnetic stimulation (rTMS) in relieving Gulf War Illness related headaches and pain.
Detailed Description
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). 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 headaches, muscle, and joint pain symptoms of GWI.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
There are two groups: one will receive active rTMS and the other group will receive sham rTMS.
Masking
ParticipantCare ProviderInvestigator
Masking Description
This is a double-blinded study where only the statistician is aware of the randomization.
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active rTMS at the LMC
Arm Type
Active Comparator
Arm Description
Subjects will receive the repetitive Transcranial Magnetic Stimulation (rTMS) study procedure at the left motor cortex (LMC)
Arm Title
Sham rTMS at the LMC
Arm Type
Sham Comparator
Arm Description
Sham rTMS will appear the same as the active, with the same parameters, but will not receive the actual magnetic stimulation to the LMC.
Intervention Type
Device
Intervention Name(s)
Transcranial Magnetic Stimulation
Intervention Description
A non-invasive treatment that emits magnetic pulses to stimulate the brain.
Intervention Type
Device
Intervention Name(s)
Sham Transcranial Magnetic Stimulation
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change from baseline to post treatment of GWI-related pain and headaches
Description
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.
Time Frame
Baseline, 1-week, 1-month, 2-month, and 3-month
Title
Change from baseline to post treatment of sensory and affective aspects of pain
Description
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.
Time Frame
Baseline, 1-week, 1-month, 2-month, and 3-month
Title
Change from baseline to post treatment of headaches
Description
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.
Time Frame
Baseline, 1-week, 1-month, 2-month, and 3-month
Title
Change from baseline to post treatment of quality of life
Description
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.
Time Frame
Baseline, 1-week, 1-month, 2-month, and 3-month
Title
Change from baseline to post treatment of body pain
Description
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").
Time Frame
Baseline, 1-week, 1-month, 2-month, and 3-month
Title
Change from baseline to post treatment of muscle pain
Description
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.
Time Frame
Baseline, 1-week, 1-month, 2-month, and 3-month
Title
Change from baseline to post treatment of fibromyalgia
Description
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."
Time Frame
Baseline, 1-week, 1-month, 2-month, and 3-month
Title
Change from baseline to post treatment of neurobehavioral symptoms
Description
Baseline, 1-week, 1-month, 2-month, and 3-month
Time Frame
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.
Title
Change from baseline to post treatment of sleep quality
Description
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."
Time Frame
Baseline, 1-week, 1-month, 2-month, and 3-month
Title
Change from baseline to post treatment of sleep difficulties
Description
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.
Time Frame
Baseline, 1-week, 1-month, 2-month, and 3-month
Title
Change from baseline to post treatment of fatigue
Description
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."
Time Frame
Baseline, 1-week, 1-month, 2-month, and 3-month
Secondary Outcome Measure Information:
Title
Change from baseline to post treatment of PTSD symptoms
Description
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
Time Frame
Baseline, 1-week, 1-month, 2-month, and 3-month
Title
Change in opioid-based pain medication usage
Description
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 VA San Diego Healthcare System 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.
Time Frame
Baseline, 1-week, 1-month, 2-month, and 3-month
Title
Explore changes in supraspinal resting state functional connectivity
Description
The outcome measure will be assessed through functional magnetic imaging scans and subsequent processing.
Time Frame
Baseline and 1-week post treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 Center for Disease Control (CDC) Criteria for Gulf War Illness (GWI) Kansas Criteria for GWI International Headache Society Criteria for Migraine Headache without aura Average Headache Exacerbation Intensity >3 on 0-10 a Numerical Pain Rating scale (NPS) 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 3 times per week with the average intensity >3 on a 0-10 NPS, lasting > 4 hours in the past three months Hamilton Rating Scale of Depression (HRSD) <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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Caleb Lopez, BS
Phone
858-552-8585
Ext
2638
Email
caleb.lopez@va.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Albert Leung, M.D.
Organizational Affiliation
San Diego Veterans Healthcare System
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Palo Alto
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Valentino Basilio
Phone
650-514-6614
Email
Vbasilio@pavir.org
First Name & Middle Initial & Last Name & Degree
Maheen Adamson, PhD
Facility Name
VA San Diego Healthcare System
City
San Diego
State/Province
California
ZIP/Postal Code
92161
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caleb Lopez, BS
Phone
858-552-8585
Ext
2638
Email
caleb.lopez@va.gov
First Name & Middle Initial & Last Name & Degree
Albert Y Leung, MD
Facility Name
VA Atlanta
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carly Ragin, BS
Phone
404-321-6111
Ext
206566
Email
Carly.Ragin@va.gov
First Name & Middle Initial & Last Name & Degree
Anna Woodbury, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Long Term Efficacy of Neuronavigation Guided rTMS in Alleviating Gulf War Illness Related Headaches and Pain Symptoms

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