Understanding GWI: Integrative Modeling

Understanding Gulf War Illness: An Integrative Modeling Approach

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.

Study Overview

• Status: Unknown
• Conditions: Occupational Diseases; Persian Gulf Syndrome; Gulf War Illness
• Intervention / Treatment: Drug: Etanercept; Drug: Mifepristone

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).

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Amanpreet Cheema, PhD; Phone Number: 954-262-2871; Email: acheema@nova.edu
• Study Contact Backup: Name: Fanny Collado, RN; Phone Number: 6706 305-575-7000; Email: fanny.collado@va.gov

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33125
      • Recruiting
      • Miami VA Healthcare System
      • Contact: Amanpreet Cheema, PhD; Phone Number: 954-262-2871; Email: acheema@nova.edu
      • Contact: Fanny Collado, RN; Phone Number: 6706 305-575-7000; Email: fanny.collado@va.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Etanercept; 50 MG/ML Prefilled Syringe (once a week for 4 weeks)	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.; Other Names: Enbrel
Experimental: Mifepristone; (300 mg once a day for 7 days) will follow the etanercept.	Drug: 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.; Other Names: Mifeprex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker response to therapy using Cytokine panel	Goal is decreased inflammation	Change from Baseline at 6 weeks and 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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]

Collaborators and Investigators

• Sponsor: South Florida Veterans Affairs Foundation for Research and Education
• Collaborators: United States Department of Defense; Nova Southeastern University
• Investigators: Principal Investigator: Nancy Klimas, MD, South Florida Veterans Affairs Foundation for Research and Education

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2017
• Primary Completion (Actual): August 15, 2019
• Study Completion (Anticipated): August 30, 2020

Study Registration Dates

• First Submitted: August 24, 2018
• First Submitted That Met QC Criteria: January 31, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: January 31, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Anti-neuroinflammatory; Homeostatic regulation; HPA axis regulator
• Additional Relevant MeSH Terms: Persian Gulf Syndrome; Occupational Diseases; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Abortifacient Agents; Luteolytic Agents; Abortifacient Agents, Steroidal; Contraceptives, Postcoital, Synthetic; Contraceptives, Postcoital; Menstruation-Inducing Agents; Etanercept; Mifepristone
• Other Study ID Numbers: 4987.84

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No