Validating Gulf War Illness Blood Biomarkers

Study Overview
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Brief Summary
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The investigators goals are to identify blood lipids/metabolites that correlate with cognitive decline in the presence of the APOE ε4 allele among veterans with GWI. To determine the effect of dietary, medical and biological factors that influence lipid and metabolites in blood from GW veterans. To identify blood lipid/metabolite profiles that correlate with bioenergetics deficits and glial activation in the brains of GWI. To validate blood biomarker signatures of GWI using APOE genotyping and blood lipids/metabolites that correlate with the CNS dysfunction in GWI.

Detailed Description
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Nearly 30 years later, veterans with Gulf War Illness (GWI) continue to suffer from this persistent and debilitating illness, which remains difficult to diagnose due to the heterogeneity of clinical presentation and the complexity of biological responses to hazardous chemicals to which GW veterans were exposed during the 1990-1991 Gulf War (GW). Brain imaging studies of veterans with GWI and pre-clinical animal studies of rodents with GWI show that impaired bioenergetics and inflammation can be attributed to the atrophy of the axonal white matter tracts that link the cortical gray matter regions, and the alterations of lipid/metabolite levels. The investigators recent work shows that disturbed lipid profiles in the brain and blood after GW pesticide exposure in rodents accompany neurobehavioral and bioenergetics deficits and inflammation. The mechanisms of neurotoxicity after pesticide exposure include increases in the inactivation of lipid metabolizing enzymes. This may consequently result in accumulation of lipids in the body compartments that limit their availability for use as energy substrates, contributing to bioenergetic impairments and inflammation. These metabolic changes have also been linked to individuals who possess the apolipoprotein E (APOE) ε4 allele, a risk factor of aging related cognitive decline and neurodegenerative conditions, such as Alzheimer's disease (AD). Several studies have shown a correlation between lipid transport deficits and presence of the ε4 allele. The identification of specific lipids/metabolites and the APOE ε4 allele as important biomarkers of GWI would serve to objectively assess the brain pathology of GWI and identify subgroups of GWI based on symptom patterns and GW exposures.

Official Title
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Validating Blood Biomarkers of Brain Immune and Metabolic Dysfunction in Gulf War Illness

Conditions
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Gulf War Syndrome, Gulf War Illness

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 35 years or older. For GWI cases, served in the 1990-1991 Gulf War as active duty, national guard, or reserves and meet criteria for the CDC Chronic Multisymptom Illness (CMI) GWI definition or Kansas GWI definition. For controls, must be a veteran in the same age range as those veterans with GWI as defined above. Ability to understand written and spoken English or availability of a legal representative who can understand written or spoken English. Participants and caregiver/informants must be able to read, write and speak the language in which psychometric tests are provided with visual and auditory acuity (corrected) sufficient to allow for accurate testing. Exclusion Criteria: Diagnosed or being treated by a physician for any of the following (Steele et al, 2000) and deemed clinically significant per the discretion of the PI: Cancer (except for non-melanoma skin cancers) Chronic infectious disease Problems resulting from postwar injuries. Liver disease Lupus Multiple sclerosis Stroke Serious psychiatric condition (those associated with psychosis and/or for which the respondent had been hospitalized since 1991). Dementia or any type of Parkinson's disease (PD). Hospitalized in the last 5 years for alcohol or drug dependence, depression, or post-traumatic stress disorder (PTSD). Female subject is either pregnant or nursing.

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Case: GWI<br>This group includes participants who served in the Gulf War during 1990 -1991 and have Gulf War Illness based on either the Kansas or CDC symptom criteria. | |
| Control<br>This group includes participants who served in the Gulf War during 1990 -1991 and have no symptoms of Gulf War Illness based on both the Kansas and CDC symptom criteria. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Validate Blood Biomarkers | To validate blood biomarker signatures of GWI using APOE genotyping and blood lipids/metabolites that correlate with the CNS dysfunction in GWI. | 2022-2024 | 
| Identify Blood/Lipid Profiles | To identify blood lipid/metabolite profiles that correlate with bioenergetics deficits and glial activation in the brains of GWI. | 2022-2024 | 
| Effect of Dietary, Medical and Biological Factors | To determine the effect of dietary, medical and biological factors that influence lipid and metabolites in blood from GW veterans. | 2022-2024 | 
| Metabolites Correlating with Cognitive Decline | To identify blood lipids/metabolites that correlate with cognitive decline in the presence of the APOE ε4 allele among veterans with GWI. | 2022-2024 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gulf War, APOE