Gulf War Illness Inflammation Reduction Trial

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Gulf War Illness Inflammation Reduction Trial

Conditions
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Chronic Inflammation, Chronic Pain, Fatigue, Cognitive Impairment

Intervention / Treatment
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* Drug: Modified-Release Prednisone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gulf War Illness, Chronic Inflammation, Modified-Release Prednisone, Health-Related Quality of Life