An observational study in Gulf War Syndrome, sponsored by University of Alabama at Birmingham. Completed at 1 site in United States. Open to male participants aged 46 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-01-13.
Sponsored by University of Alabama at Birmingham · Observational
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.
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.
39 studies on the registry are indexed under Persian Gulf Syndrome; 10 are open to participants now.
Browse Persian Gulf Syndrome studies →University of Alabama at Birmingham is the lead sponsor of 1,416 studies on the registry; 278 are open to participants now.
Of its 160 completed or terminated interventional studies of FDA-regulated products, 128 (80%) have results posted.
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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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
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.
Procedure: Magnetic Resonance Spectroscopic Imaging · Procedure: Blood draw
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.
Procedure: Magnetic Resonance Spectroscopic Imaging · Procedure: Blood draw
MRSI is a non invasive imaging technique used to detect neuroinflammation.
Also known as: MRSI
Blood will be drawn to assess systemic inflammation in Gulf War verterans.
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 20 minutes
| Milestone | Healthy Control | Gulf War Illness |
|---|---|---|
| Started | 21 | 28 |
| Completed | 20 | 25 |
| Not completed | 1 | 3 |
| Withdrew: Withdrawal by subject | 1 | 3 |
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.
| Institutional Units (IU) | Healthy Control | Gulf War Illness |
|---|---|---|
| Concentration of Myoinositol in the Brain | 0.001260 ± 0.0002362 | 0.001205 ± 0.0001699 |
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.
| Institutional Units (IU) | Healthy Control | Gulf War Illness |
|---|---|---|
| Concentration of Lactate in the Brain | 0.0003886 ± 0.0001629 | 0.0005388 ± 0.000365 |
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.
| Institutional Units (IU) | Healthy Control | Gulf War Illness |
|---|---|---|
| Concentration of Choline in the Brain | 0.0003838 ± 0.000051446 | 0.0003499 ± 0.000034982 |
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.
| Institutional Units (IU) | Healthy Control | Gulf War Illness |
|---|---|---|
| Concentration of N-acetylaspartate in the Brain | 0.0023191 ± 0.0001821 | 0.0022186 ± 0.0001721 |
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.
| degrees Celsius | Healthy Control | Gulf War Illness |
|---|---|---|
| Temperature in the Brain | 36.622 ± 0.322 | 36.826 ± 0.331 |
Collected over 24 hours. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Healthy Control | 0/21 (0%) | 0/21 (0%) | 0/21 (0%) |
| Gulf War Illness | 0/28 (0%) | 0/28 (0%) | 0/28 (0%) |
| Age, Categorical(Participants) | Healthy Control | Gulf War Illness | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 21 | 28 | 49 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Healthy Control | Gulf War Illness | Total |
|---|---|---|---|
| Female | 0 | 0 | 0 |
| Male | 21 | 28 | 49 |
| Race (NIH/OMB)(Participants) | Healthy Control | Gulf War Illness | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 1 | 1 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 1 | 1 |
| Black or African American | 1 | 2 | 3 |
| White | 19 | 23 | 42 |
| More than one race | 1 | 1 | 2 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Healthy Control | Gulf War Illness | Total |
|---|---|---|---|
| United States | 21 | 28 | 49 |
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