Clinical trial NCT04255498: Understanding GWI: Integrative Modeling
Official title: Understanding Gulf War Illness: An Integrative Modeling Approach
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Gulf War Illness
Persian Gulf Syndrome
Occupational Diseases
Keywords: Anti-neuroinflammatory
Homeostatic regulation
HPA axis regulator
Lead sponsor: South Florida Veterans Affairs Foundation for Research and Education
Sponsor class: FED
Collaborators: name: Nova Southeastern University
name: United States Department of Defense
First posted: 2020-02-05
Enrollment: 20
Sex: MALE
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Perform Phase I study of etanercept (50 mg, once a week for 4 weeks), followed by mifepristone (300 mg, once a day for 7 days), followed by a 10 week observation period and assessment of safety, efficacy and biomarker response to therapy.
Primary purpose: TREATMENT

Brief summary: The investigator proposes to perform a Phase I study assessing safety, efficacy, and biomarker response to the therapeutic interventions of Etanercept followed by mifepristone for veterans with Gulf War Illness. The investigator will conduct and repeat the exercise challenge before treatment and on therapy to assess the impact of the interventions on homeostatic regulation and the dynamic model identified in prior studies.

Detailed description: In the Investigator's prior work, the investigator used an exercise stress model (rest, peak oxygen consumption oxygen uptake, and 7 follow-up sampling points) to measure the mediators of relapse in the context of their interactive homeostatic networks. The investigator surveyed the response of genes and blood-borne biomarkers in order to interrogate and map the regulation of neuro-endocrine-autonomic-immune function in these subjects as compared to GW era sedentary healthy controls. This study is the first to test in the GWI human system of the impact of interventions that hope to permanently re-set the key pathway(s) involved in maintaining a "sick" homeostatic network in Gulf War Illness, discovered in our prior CDMRP and VA funded projects. An open-label Phase I study will be performed with Etanercept (once a week for 4 weeks) followed by mifepristone (once a day for 7 days), followed by a 10-week observation to assess safety, efficacy and biomarker response to maximal exercise. The impact of the interventions will be measured on current computational modeling of dynamic response GWI illness mediators at onset, at 6 weeks (on completion of the medication regimen) and 4 months after baseline; using 20 GWI patients. The response during and after an exercise challenge will be assessed followed by map the homeostatic networks in play over the 24 hours post-exercise in subjects before treatment, after completing the second treatment (week 6) and 4 months after initiating treatment (week 16).

Eligibility criteria: Inclusion Criteria:

* Male Veterans who were deployed in 1990 -1991 Gulf War.
* Veterans who currently meet the Kansas Gulf War Study Case Definition for Gulf War Illness.
* Veterans who were in good health based on medical history prior to 1990.
* Veterans who are between 40 to 70 years old
* Veterans who currently do not have exclusionary diagnoses that could reasonably explain the symptoms of their fatiguing illness and their severity.

Exclusion Criteria:

* Major depression with psychotic or melancholic features
* Schizophrenia
* Bipolar disorder
* Delusional disorders
* Dementias of any type
* History or current alcohol abuse
* History or current drug abuse
* Organ failure
* Transplant
* Defined rheumatologic
* Inflammatory disorders
* HIV
* Hepatitis B and C
* Primary sleep disorders
* Steroids
* Immunosuppressives
* Medications that impact immune function such as Enbrel or Methotrexate
* Tuberculosis or past history of tuberculosis exposure, as documented by PPD positivity

Primary outcomes:
measure: Biomarker response to therapy using Cytokine panel
timeFrame: Change from Baseline at 6 weeks and 16 weeks
Secondary outcomes:
measure: Biomarker response too therapy using VO2 exercise test
timeFrame: Change from Baseline at 6 weeks and 16 weeks]
Other outcomes:
Locations:
city: Miami
country: United States
facility: Miami VA Healthcare System
state: Florida
Study officials:
affiliation: South Florida Veterans Affairs Foundation for Research and Education
name: Nancy Klimas, MD
role: PRINCIPAL_INVESTIGATOR
References: