Understanding GWI: Integrative Modeling

Gulf War Illness Clinical Trial

Official title:

Understanding Gulf War Illness: An Integrative Modeling Approach

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04255498
• Other study ID #: 4987.84
• Status: Recruiting
• Phase: Phase 1
• Start date: October 30, 2017
• Est. completion date: August 30, 2020

Study information

• Verified date: January 2020
• Source: South Florida Veterans Affairs Foundation for Research and Education
• Contact: Fanny Collado, RN
• Phone: 305-575-7000
• Email: fanny.collado[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: August 30, 2020
• Est. primary completion date: August 15, 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Gulf War Illness
• Occupational Diseases
• Persian Gulf Syndrome

Intervention

Drug:
• Etanercept
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. Perform dynamic modeling studies before and after 5 weeks of therapy, repeating the method used previously, in order to document the response to exercise and better quantify the degree of recovery in treated subjects using an exercise challenge and 9 point in time with blood and saliva collections over 24 hours with genomic, cytokine, neuropeptide and cell population studies.
• Mifepristone
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. Perform dynamic modeling studies before and after 5 weeks of therapy, repeating the method used previously, in order to document the response to exercise and better quantify the degree of recovery in treated subjects using an exercise challenge and 9 point in time with blood and saliva collections over 24 hours with genomic, cytokine, neuropeptide and cell population studies.

Locations

Country	Name	City	State
United States	Miami VA Healthcare System	Miami	Florida

Sponsors (3)

Lead Sponsor	Collaborator
South Florida Veterans Affairs Foundation for Research and Education	Nova Southeastern University, United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biomarker response to therapy using Cytokine panel	Goal is decreased inflammation	Change from Baseline at 6 weeks and 16 weeks
Secondary	Biomarker response too therapy using VO2 exercise test	Goal is that both will prove safe for use in GWI patients	Change from Baseline at 6 weeks and 16 weeks]