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NCT Number: NCT05736146

Validating Gulf War Illness Blood Biomarkers

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.

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Key information

Age range

35 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Palto Alto Veterans Institute for Research, Palo Alto, California, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Primary outcomes

  1. Validate Blood Biomarkers

    Time frame: 2022-2024

    To validate blood biomarker signatures of GWI using APOE genotyping and blood lipids/metabolites that correlate with the CNS dysfunction in GWI.

  2. Identify Blood/Lipid Profiles

    Time frame: 2022-2024

    To identify blood lipid/metabolite profiles that correlate with bioenergetics deficits and glial activation in the brains of GWI.

  3. Effect of Dietary, Medical and Biological Factors

    Time frame: 2022-2024

    To determine the effect of dietary, medical and biological factors that influence lipid and metabolites in blood from GW veterans.

  4. Metabolites Correlating with Cognitive Decline

    Time frame: 2022-2024

    To identify blood lipids/metabolites that correlate with cognitive decline in the presence of the APOE ε4 allele among veterans with GWI.

Study contacts

Contact information is provided by the study sponsor or research team.

Dakota Helgager, B.S

CONTACT

[email protected]

(941) - 256 - 8019 ext. 3008

Sponsors and collaborators

Lead sponsor

Roskamp Institute Inc.

Other

Collaborators

  • Boston University
  • Palo Alto Veterans Institute for Research
  • United States Department of Defense

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2025
Study completion
2026
First posted
Feb 21, 2023
Registry last updated
Jul 24, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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