Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04638998 |
| Other study ID # |
IRB-3000004528 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
December 1, 2020 |
| Est. completion date |
December 31, 2023 |
Study information
| Verified date |
January 2024 |
| Source |
University of Alabama at Birmingham |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical 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 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.
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.
