Clinical trial NCT05736146: Validating Gulf War Illness Blood Biomarkers
Official title: Validating Blood Biomarkers of Brain Immune and Metabolic Dysfunction in Gulf War Illness
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Gulf War Syndrome
Gulf War Illness
Keywords: Gulf War
APOE
Lead sponsor: Roskamp Institute Inc.
Sponsor class: OTHER
Collaborators: name: Boston University
name: Palo Alto Veterans Institute for Research
name: United States Department of Defense
First posted: 2023-02-21
Enrollment: 100
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Veterans who served in the Gulf War during 1990 to 1991.

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Age 35 years or older.
2. 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.
3. For controls, must be a veteran in the same age range as those veterans with GWI as defined above.
4. 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:

1. 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:

   1. Cancer (except for non-melanoma skin cancers)
   2. Chronic infectious disease
   3. Problems resulting from postwar injuries.
   4. Liver disease
   5. Lupus
   6. Multiple sclerosis
   7. Stroke
   8. Serious psychiatric condition (those associated with psychosis and/or for which the respondent had been hospitalized since 1991).
   9. Dementia or any type of Parkinson's disease (PD).
2. Hospitalized in the last 5 years for alcohol or drug dependence, depression, or post-traumatic stress disorder (PTSD).
3. Female subject is either pregnant or nursing.

Primary outcomes:
measure: Validate Blood Biomarkers
timeFrame: 2022-2024
measure: Identify Blood/Lipid Profiles
timeFrame: 2022-2024
measure: Effect of Dietary, Medical and Biological Factors
timeFrame: 2022-2024
measure: Metabolites Correlating with Cognitive Decline
timeFrame: 2022-2024
Secondary outcomes:
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Palto Alto Veterans Institute for Research
state: California
city: Sarasota
country: United States
facility: The Roskamp Institute
state: Florida
city: Boston
country: United States
facility: Boston University
state: Massachusetts
Study officials:
affiliation: The Roskamp Institute
name: Laila Abdullah, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Roskamp Institute
name: Michael Hoffmann, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston University
name: Kim Sullivan, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Palo Alto Veterans Institute of Research
name: Maheen Adamson, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: