Gulf War SyndromeNCT04638998
Assessing Neuroinflammation in GWI Using MRS
An observational study of Gulf War Syndrome, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
The primary aim of this study is to determine if Gulf War Illness (GWI) likely involves neuroinflammation. The investigators hypothesize that GWI involves neuroinflammation. By assessing the five neuroinflammatory outcomes across the brain, the investigators can determine if there are focal or global signs of one or… Read more about this study
- Who is it for?
- Ages 46 to 70 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Gulf War Syndrome
- What is being tested?
- Magnetic Resonance Spectroscopic Imaging and Blood draw
- Type of treatment
- Surgery or procedure
- How many people
- 49 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2020to 31 Dec 2023
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 46 to 70 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Study population: This study requires the recruitment of Gulf War Veterans who were present in the Persian Gulf between 1990 and August 1991 and who were forward deployed to either Iraq or Kuwait. Of the approximate 650,000 service members who served in the Gulf War, only around 50,000 were women. As the number of female veterans who fit the study criteria wanes in comparison to that of the male veterans, it would prove extremely difficult to recruit both GWI and age-matched, healthy control female veterans. To circumvent this issue, the investigators chose to use only male Gulf War veterans for our study.
Who may be able to join
- Between the ages of 46 and 70
- Veterans who meet the Kansas inclusion criteria .The Kansas Inclusion Criteria are a set of the most frequently reported symptoms experienced by Gulf War veterans. This frequency and severity of the symptoms reported by the participant indicate whether the person has Gulf War Illness or not. The Kansas Inclusion Criteria is the gold standard for identifying veterans with GWI in the field. The criteria are attached.
- Present in Persian Gulf between 1990 and August 1991
- Forward deployed (in Iraq or Kuwait)
Who cannot join
- Usage of experimental medications, opioid analgesics, psychostimulants (except caffeine), or benzodiazepines
- Uncontrolled diabetes, autoimmune disorders, and thyroid disorders.
- Major cardiovascular illness, cancer, or have any contraindications for MRI (including metallic implants or claustrophobia)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35294
About this study
Official title: Assessing Neuroinflammation in Gulf War Illness With Whole-Brain Magnetic Resonance Spectroscopy
The primary aim of this study is to determine if Gulf War Illness (GWI) likely involves neuroinflammation. The investigators hypothesize that GWI involves neuroinflammation. By assessing the five neuroinflammatory outcomes across the brain, the investigators can determine if there are focal or global signs of one or more neuroinflammatory markers in the brains of individuals with GWI. This neuroimaging technique may allow investigators and others to detect cases of GWI neuroinflammation, which would improve treatment decisions as well as the development of new targeted therapies. It is an ideal diagnostic tool because it has low patient risk, is noninvasive, can be used repeatedly in longitudinal studies, provides whole-brain coverage, yields multiple independent markers of inflammation, and can be employed at most hospitals and research neuroimaging suites.
Read the detailed description
This proposal is for a Tier 1 (Discovery) study that uses a human, cross-sectional, observational neuroimaging approach to measure neuroinflammation in Gulf War Illness (GWI). A whole-brain magnetic resonance spectroscopic imaging (MRSI) scan will be used to detect multiple markers of neuroinflammation in 30 individuals with GWI and 30 healthy veteran controls. The investigators have fully tested the MRSI scan in several patient groups, and have found strong evidence of neuroinflammation in fibromyalgia and chronic fatigue syndrome - conditions the investigators believe involve abnormal central immune system processing. The investigators have not, however, performed the scan on individuals with GWI. The discovery study will allow investigators to transfer this existing technology to the GWI field. This project meets the core Special Interest of investigating dysregulation between the immune and neurological systems in the brain.
The investigators' central hypothesis is that GWI involves chronic neuroinflammation. The symptoms of GWI (e.g. fatigue, musculoskeletal pain, sleep disturbances, and cognitive dysfunction) overlap heavily with classic cytokine-induced sickness responses. In the case of GWI, microglial cells in the brain can be pushed into a hypersensitized state by toxins or abnormal immune challenges, leading to chronic overproduction of pro-inflammatory factors that result in the primary symptoms of GWI.
To test the central hypothesis, it is necessary to measure neuroinflammation in humans in vivo. However, most techniques are too invasive for use in living individuals. To address that problem, the investigators use an MRSI scan which provides metabolite concentrations in 4,000 separate voxels, giving whole-brain coverage. The scan yields measurements for: Myo-inositol (a marker of glial cell proliferation), lactate (a product of anaerobic metabolism), choline (a sign of cellular breakdown), and N-acetylaspartate (a marker of neuronal health). The scan also provides absolute brain temperature, which is shown to be elevated with severe neuroinflammation. The five main outcomes are as follows:
Myo-inositol (MI): Higher values represent greater microglia proliferation or gliosis.
Lactate (Lac): Higher values represent more severe inflammatory activity.
Choline (Cho): Higher values indicate greater cell turnover (inflammation, gliosis, or demyelination).
NAA: Lower values represent neurodegeneration.
Temperature: Higher values represent greater neuroinflammation. Metabolite and water-reference data will be analyzed using the MIDAS package and thermometry extension41. Absolute brain temperatures (in °C) within each voxel will be calculated by measuring the distance of the temperature-invariant NAA peak from the temperature-variant water peak using the formula: Tbrain = -102.76 × Δwater-NAA + 310.5°C, which has been validated in our scanner to produce reliable readings. Temperature will be expressed on absolute values in °C.
- Conditions
- Gulf War Syndrome
- Being tested
- Magnetic Resonance Spectroscopic Imaging, Blood draw
- Keywords
- neuroinflammation, Gulf War Illness
- Medical subject headings
- Persian Gulf Syndrome, Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic Resonance Spectroscopic ImagingProcedure or surgery
Also called MRSI
MRSI is a non invasive imaging technique used to detect neuroinflammation.
Blood drawProcedure or surgery
Blood will be drawn to assess systemic inflammation in Gulf War verterans.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Control | The healthy control group are men ages 46-70 who were present in the Persian Gulf War between 1990 and August 1991. This cohort do not experience any Gulf War Illness symptoms. Receives: Procedure: Magnetic Resonance Spectroscopic Imaging; Procedure: Blood draw | |
| Gulf War Illness | The GWI cohort are men ages 46-70 who were present in the Persian Gulf War between 1990 and August 1991. The men in this cohort will also meet the Kansas Inclusion Criteria for GWI. Receives: Procedure: Magnetic Resonance Spectroscopic Imaging; Procedure: Blood draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of Myoinositol in the Brain
The concentration of myoinositol will be measured in the brain using MRI as a measure of neuroinflammation. This will be measured in both the control and experimental groups.
Measured: 20 minutes
Concentration of Lactate in the Brain
The concentration of lactate will be measured in the brain using MRI as a measure of neuroinflammation. The concentration will be expressed in water-normed "Institutional Units". This will be measured in both the control and experimental groups. Values are expressed as metabolites averaged across the cortical lobes and cerebellum.
Measured: 20 minutes
Concentration of Choline in the Brain
The concentration of choline will be measured in the brain using MRI as a measure of neuroinflammation. This will be measured in both the control and experimental groups.
Measured: 20 minutes
Concentration of N-acetylaspartate in the Brain
The concentration of N-acetylaspartate will be measured in the brain using MRI as a measure of neuroinflammation. This will be measured in both the control and experimental groups.
Measured: 20 minutes
Temperature in the Brain
The temperature of the brain will be measured using MRI as a measure of neuroinflammation. This will be measured in both the control and experimental groups. An amplitude-weighted combination of NAA, creatine, and choline was used as the reference for temperature deviations.
Measured: 20 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2020
- Study start1 Dec 2020
- Primary completion29 Sep 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gulf War SyndromeStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Principal investigator, Jarred Younger, University of Alabama at Birmingham
- Investigators
- Jarred Younger, PhD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04638998
- Sponsor's protocol ID
- IRB-3000004528
- Other IDs
- W81XWH-19-1-0725
- Status last verified
- Nov 2024
- First submitted
- 16 Nov 2020
- Last updated
- 13 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Jones C, Haskin O, Younger J. Neurometabolite alterations in Gulf War Illness: a whole-brain magnetic resonance spectroscopy study. Exp Brain Res. 2025 Oct 25;243(11):237. doi: 10.1007/s00221-025-07174-w.
PubMed 41137912
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing Neuroinflammation in Gulf War Illness With Whole-Brain Magnetic Resonance Spectroscopy
- ClinicalTrials.gov ID
- NCT04638998
- Acronym / sponsor ID
- IRB-3000004528
- Conditions
- Gulf War Syndrome
- Keywords
- neuroinflammation, Gulf War Illness
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- 1 Dec 2020 (actual)
- Primary completion
- 29 Sep 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 20 Nov 2020 (actual)
- Results
- Posted 13 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary aim of this study is to determine if Gulf War Illness (GWI) likely involves neuroinflammation. The investigators hypothesize that GWI involves neuroinflammation. By assessing the five neuroinflammatory outcomes across the brain, the investigators can determine if there are focal or global signs of one or more neuroinflammatory markers in the brains of individuals with GWI. This neuroimaging technique may allow investigators and others to detect cases of GWI neuroinflammation, which would improve treatment decisions as well as the development of new targeted therapies. It is an ideal diagnostic tool because it has low patient risk, is noninvasive, can be used repeatedly in longitudinal studies, provides whole-brain coverage, yields multiple independent markers of inflammation, and can be employed at most hospitals and research neuroimaging suites.
Detailed description
This proposal is for a Tier 1 (Discovery) study that uses a human, cross-sectional, observational neuroimaging approach to measure neuroinflammation in Gulf War Illness (GWI). A whole-brain magnetic resonance spectroscopic imaging (MRSI) scan will be used to detect multiple markers of neuroinflammation in 30 individuals with GWI and 30 healthy veteran controls. The investigators have fully tested the MRSI scan in several patient groups, and have found strong evidence of neuroinflammation in fibromyalgia and chronic fatigue syndrome - conditions the investigators believe involve abnormal central immune system processing. The investigators have not, however, performed the scan on individuals with GWI. The discovery study will allow investigators to transfer this existing technology to the GWI field. This project meets the core Special Interest of investigating dysregulation between the immune and neurological systems in the brain.
The investigators' central hypothesis is that GWI involves chronic neuroinflammation. The symptoms of GWI (e.g. fatigue, musculoskeletal pain, sleep disturbances, and cognitive dysfunction) overlap heavily with classic cytokine-induced sickness responses. In the case of GWI, microglial cells in the brain can be pushed into a hypersensitized state by toxins or abnormal immune challenges, leading to chronic overproduction of pro-inflammatory factors that result in the primary symptoms of GWI.
To test the central hypothesis, it is necessary to measure neuroinflammation in humans in vivo. However, most techniques are too invasive for use in living individuals. To address that problem, the investigators use an MRSI scan which provides metabolite concentrations in 4,000 separate voxels, giving whole-brain coverage. The scan yields measurements for: Myo-inositol (a marker of glial cell proliferation), lactate (a product of anaerobic metabolism), choline (a sign of cellular breakdown), and N-acetylaspartate (a marker of neuronal health). The scan also provides absolute brain temperature, which is shown to be elevated with severe neuroinflammation. The five main outcomes are as follows:
Myo-inositol (MI): Higher values represent greater microglia proliferation or gliosis.
Lactate (Lac): Higher values represent more severe inflammatory activity.
Choline (Cho): Higher values indicate greater cell turnover (inflammation, gliosis, or demyelination).
NAA: Lower values represent neurodegeneration.
Temperature: Higher values represent greater neuroinflammation. Metabolite and water-reference data will be analyzed using the MIDAS package and thermometry extension41. Absolute brain temperatures (in °C) within each voxel will be calculated by measuring the distance of the temperature-invariant NAA peak from the temperature-variant water peak using the formula: Tbrain = -102.76 × Δwater-NAA + 310.5°C, which has been validated in our scanner to produce reliable readings. Temperature will be expressed on absolute values in °C.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy Control | – | Procedure: Magnetic Resonance Spectroscopic Imaging, Procedure: Blood drawThe healthy control group are men ages 46-70 who were present in the Persian Gulf War between 1990 and August 1991. This cohort do not experience any Gulf War Illness symptoms. |
| Gulf War Illness | – | Procedure: Magnetic Resonance Spectroscopic Imaging, Procedure: Blood drawThe GWI cohort are men ages 46-70 who were present in the Persian Gulf War between 1990 and August 1991. The men in this cohort will also meet the Kansas Inclusion Criteria for GWI. |
Who may qualify
- Ages
- 46 to 70 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- This study requires the recruitment of Gulf War Veterans who were present in the Persian Gulf between 1990 and August 1991 and who were forward deployed to either Iraq or Kuwait. Of the approximate 650,000 service members who served in the Gulf War, only around 50,000 were women. As the number of female veterans who fit the study criteria wanes in comparison to that of the male veterans, it would prove extremely difficult to recruit both GWI and age-matched, healthy control female veterans. To circumvent this issue, the investigators chose to use only male Gulf War veterans for our study.
Key inclusion criteria (4 listed)
- Between the ages of 46 and 70
- Veterans who meet the Kansas inclusion criteria .The Kansas Inclusion Criteria are a set of the most frequently reported symptoms experienced by Gulf War veterans. This frequency and severity of the symptoms reported by the participant indicate whether the person has Gulf War Illness or not. The Kansas Inclusion Criteria is the gold standard for identifying veterans with GWI in the field. The criteria are attached.
- Present in Persian Gulf between 1990 and August 1991
- Forward deployed (in Iraq or Kuwait)
Key exclusion criteria (3 listed)
- Usage of experimental medications, opioid analgesics, psychostimulants (except caffeine), or benzodiazepines
- Uncontrolled diabetes, autoimmune disorders, and thyroid disorders.
- Major cardiovascular illness, cancer, or have any contraindications for MRI (including metallic implants or claustrophobia)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Magnetic Resonance Spectroscopic ImagingAlso: MRSIMRSI is a non invasive imaging technique used to detect neuroinflammation. | Procedure or surgery | Gulf War Illness, Healthy Control |
| Blood drawBlood will be drawn to assess systemic inflammation in Gulf War verterans. | Procedure or surgery | Gulf War Illness, Healthy Control |
Primary outcome
Concentration of Myoinositol in the Brain
Time frame: 20 minutes
The concentration of myoinositol will be measured in the brain using MRI as a measure of neuroinflammation. This will be measured in both the control and experimental groups.
Concentration of Lactate in the Brain
Time frame: 20 minutes
The concentration of lactate will be measured in the brain using MRI as a measure of neuroinflammation. The concentration will be expressed in water-normed "Institutional Units". This will be measured in both the control and experimental groups. Values are expressed as metabolites averaged across the cortical lobes and cerebellum.
Concentration of Choline in the Brain
Time frame: 20 minutes
The concentration of choline will be measured in the brain using MRI as a measure of neuroinflammation. This will be measured in both the control and experimental groups.
Concentration of N-acetylaspartate in the Brain
Time frame: 20 minutes
The concentration of N-acetylaspartate will be measured in the brain using MRI as a measure of neuroinflammation. This will be measured in both the control and experimental groups.
Temperature in the Brain
Time frame: 20 minutes
The temperature of the brain will be measured using MRI as a measure of neuroinflammation. This will be measured in both the control and experimental groups. An amplitude-weighted combination of NAA, creatine, and choline was used as the reference for temperature deviations.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41137912Jones C, Haskin O, Younger J. Neurometabolite alterations in Gulf War Illness: a whole-brain magnetic resonance spectroscopy study. Exp Brain Res. 2025 Oct 25;243(11):237. doi: 10.1007/s00221-025-07174-w.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jarred Younger, PhD principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Gulf War Syndrome, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentration of Myoinositol in the Brain (time frame: 20 minutes). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04638998, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2025.