Gulf War Illness Inflammation Reduction Trial (GWIIRT)

The primary objective of this clinical trial is to determine if treatment with an anti-inflammatory drug (delayed-release prednisone) improves the health-related quality of life (HRQOL) of veterans with Gulf War Illness (GWI). The primary outcome measure is a change from baseline of HRQOL with respect to physical functioning and symptoms. Secondary outcomes measures include changes from baseline levels of GWI-associated biomarkers of inflammation in peripheral blood, GWI-associated symptoms (chronic pain, fatigue, and cognitive impairment), and HRQOL with respect to mental functioning.

Study Overview

• Status: Completed
• Conditions: Fatigue; Chronic Pain; Cognitive Impairment; Chronic Inflammation
• Intervention / Treatment: Drug: Modified-Release Prednisone; Drug: Placebo

Detailed Description

During Desert Shield and Desert Storm (Aug 2, 1990 to July 31,1991) 696,841 United States Military personnel were deployed to the Kuwaiti Theater of Operations. Today approximately one-third of those veterans are suffering from GWI, an unexplained chronic multi-symptom illness. Evidence of chronic inflammation in veterans with GWI has emerged from previous observational studies. The goal of this trial is to determine if reducing the GWI-associated chronic inflammation is an effective treatment for GWI. This is a randomized, two group, placebo controlled, double blind clinical trial. The treatment group will receive a low dose (2x5mg) once a day of delayed-release prednisone (Rayos) for 8 weeks. The placebo group will receive matching placebo (2x5mg) once a day for 8 weeks. The primary outcome measure for this clinical trial is a change from baseline of HRQOL with respect to physical functioning and symptoms. The secondary outcome measures include changes from baseline of peripheral blood levels of GWI-associated biomarkers of inflammation, changes from baseline of GWI-associated symptoms (chronic pain, fatigue, and cognitive impairment), and a change from baseline of HRQOL with respect to mental functioning.

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis Veterans Affairs Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Scores moderate-severe on at least 3 out of 6 domains from the Kansas GWI Case Definition
• Deployed, (and honorably discharged), from the Kuwaiti Theater of Operation (August 2, 1990-July 31, 1991)

Exclusion Criteria:

• Hospitalization anytime since 1990 for Alcohol or Drug Dependence, Depression, or PTSD
• Known hypersensitivity to Prednisone
• Liver, (active or recent Hepatitis B or C treatment with a completion date within the past 6 months, or alcohol liver disease), or Kidney Disease (Hep B and C ok if after 6 months of treatment)
• Treated Diabetes
• Females who are Pregnant or Nursing
• Female who refuses to use an accepted method of birth control
• Exclusionary Labs: C-Reactive Protein >25, Creatinine Clearance <30, EFGR ≥ 30, Hgb A1-C >7, Glucose >120, WBC >12, RBC >6.2, Hematocrit >60, Hemoglobin <11, Platelets <100, Liver Function Tests (2 x the upper limit of AST and ALT, 2 x the upper limit of Total Bilirubin, and Alkaline Phosphatase)
• Has Inflammatory Arthritis (RA, or Psoriatic Arthritis, Spondylitis, Polyarthritis)
• Reactive Arthritis, or IBD associated Arthritis
• Has any major inflammatory disease (acute Chronic Infections, Ulcerative Colitis, Crohn's Disease, Inflammatory lung diseases- COPD or Asthma requiring steroid treatment, Pericarditis, Vasculitis)
• Has an chronic/active infection
• Chronic use of Prednisone or Corticosteroids (occasional inhaled use of steroids acceptable)
• Active Gum Disease or Dental Infection
• Has been diagnosed with Lupus, Stroke, or Multiple Sclerosis. or any other diagnosis that produces symptoms of fatigue, cognitive impairment, or pain will be excluded based on the Kansas GWI Case definition
• Has a condition that may interfere with the ability to accurately report symptoms, (Severe Psychiatric Problems, Schizophrenia, Bipolar Disorder, Alcohol or Drug Dependence requiring hospitalization, or regular illegal drug use)
• Heart Disease (other than Hypertension), Heart Failure or Coronary Heart Disease requiring hospitalization within the past 12 months
• Cancer (other than basal cell skin cancer), requiring treatment within the past 12 months, or life expectancy of less than 1 year.
• Hospitalization within the past 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Modified-Release Prednisone; Take oral tablets as directed (2x5mg) with food each evening at bedtime- approximately 10:00 pm	Drug: Modified-Release Prednisone; Modified-Release Prednisone oral tablets (2x5mg) daily for 8 weeks; Other Names: Rayos
Placebo Comparator: Placebo; Take oral tablets as directed (2x5mg) with food each evening at bedtime-approximately 10:00 pm	Drug: Placebo; Placebo oral tablets (2x5mg) daily for 8 weeks; Other Names: sugar pill, inactive substance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline of Veterans RAND 36-Item Health Survey Physical Component Summary Score (PCS) Scores at 8 and 16 Weeks	The SF-36V is a modification of the well-established Medical Outcomes Study Short Form Health Survey (SF-36). It surveys eight concepts of health: physical functioning, role limitations because of physical problems, bodily pain, general health perceptions, energy/vitality, social functioning, role limitations due to emotional problems and mental health. From these concepts, two summary component scores are derived: a Physical Component Summary (PCS) and a Mental Component Summary (MCS). To calculate PCS, scales are standardized with a scoring algorithm or by the scoring software. Scores are standardized and range from 0 to 100, with a US population mean of 50 points and a SD of 10 points. The PCS and the MCS have been demonstrated to have excellent psychometric properties. SF-36V PCS is a measure of HRQOL with respect to physical functioning and symptoms. Higher scores indicate better health status,	0, 8, and 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline of McGill Pain Questionnaire-short Form (MPQ) Scores at 8 and 16 Weeks	MPQ asks questions about sensory pain, affective pain, pain now, and typical pain	0, 8, and 16 weeks
Change From Baseline of Multidimensional Fatigue Inventory (MFI) Scores at 8 and 16 Weeks	MFI asks questions about general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue.	0, 8, and 16 weeks
Change From Baseline of Cognitive Failures Questionnaire (CFQ) Scores at 8 and 16 Weeks	CFQ asks questions about cognitive symptoms such as attention, concentration, and memory	0, 8, and 16 weeks
Change From Baseline of Veterans RAND 36-Item Health Survey Mental Component Summary Score (MCS) Scores at 8 and 16 Weeks	SF-36V MCS is a measure of HRQOL with respect to mental functioning. The SF-36V is a modification of the well-established Medical Outcomes Study Short Form Health Survey (SF-36). It surveys eight concepts of health: physical functioning, role limitations because of physical problems, bodily pain, general health perceptions, energy/vitality, social functioning, role limitations due to emotional problems and mental health. From these concepts, two summary component scores are derived: a Physical Component Summary (PCS) and a Mental Component Summary (MCS). To calculate MCS, scales are standardized with a scoring algorithm or by the scoring software. Scores are standardized and range from 0 to 100, with a US population mean of 50 points and a SD of 10 points. The PCS and the MCS have been demonstrated to have excellent psychometric properties. SF-36V MCS is a measure of HRQOL with respect to mental functioning and symptoms. Higher scores indicate better health status,	0, 8, and 16 weeks
Change From Baseline of Gulf War Illness-associated Peripheral Blood Biomarkers	Peripheral blood biomarker levels are quantified by multi-analyte profiling (MAP) and complete blood count (CBC) analyses	0, 8, and 16 weeks

Collaborators and Investigators

• Sponsor: Minneapolis Veterans Affairs Medical Center
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Ronald R Bach, PhD, Minneapolis Veterans Affairs Medical Center

Publications and helpful links

General Publications

• Bach RR, Rudquist RR. Gulf war illness inflammation reduction trial: A phase 2 randomized controlled trial of low-dose prednisone chronotherapy, effects on health-related quality of life. PLoS One. 2023 Jun 15;18(6):e0286817. doi: 10.1371/journal.pone.0286817. eCollection 2023.

Helpful Links

• link to citation

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): October 19, 2023
• Study Completion (Actual): October 19, 2023

Study Registration Dates

• First Submitted: July 20, 2015
• First Submitted That Met QC Criteria: July 22, 2015
• First Posted (Estimated): July 23, 2015

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Gulf War Illness; Chronic Inflammation; Health-Related Quality of Life; Modified-Release Prednisone
• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Inflammation; Chronic Pain; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: 4554-A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After publication, all deidentified study data will be made available to other investigators upon request. Data sharing rule of the journal will apply.
• IPD Sharing Time Frame: After publication for as long as specified by the journal
• IPD Sharing Access Criteria: Established investigators with legitimate scientific credentials
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF