Clinical trial NCT02506192: Gulf War Illness Inflammation Reduction Trial
Official title: Gulf War Illness Inflammation Reduction Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Inflammation
Chronic Pain
Fatigue
Cognitive Impairment
Keywords: Gulf War Illness
Chronic Inflammation
Modified-Release Prednisone
Health-Related Quality of Life
Lead sponsor: Minneapolis Veterans Affairs Medical Center
Sponsor class: FED
Collaborators: name: United States Department of Defense
First posted: 2015-07-23
Enrollment: 83
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline of Veterans RAND 36-Item Health Survey Physical Component Summary Score (PCS) Scores at 8 and 16 Weeks
timeFrame: 0, 8, and 16 weeks
Secondary outcomes:
measure: Change From Baseline of McGill Pain Questionnaire-short Form (MPQ) Scores at 8 and 16 Weeks
timeFrame: 0, 8, and 16 weeks
measure: Change From Baseline of Multidimensional Fatigue Inventory (MFI) Scores at 8 and 16 Weeks
timeFrame: 0, 8, and 16 weeks
measure: Change From Baseline of Cognitive Failures Questionnaire (CFQ) Scores at 8 and 16 Weeks
timeFrame: 0, 8, and 16 weeks
measure: Change From Baseline of Veterans RAND 36-Item Health Survey Mental Component Summary Score (MCS) Scores at 8 and 16 Weeks
timeFrame: 0, 8, and 16 weeks
measure: Change From Baseline of Gulf War Illness-associated Peripheral Blood Biomarkers
timeFrame: 0, 8, and 16 weeks
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Minneapolis Veterans Affairs Medical Center
state: Minnesota
Study officials:
affiliation: Minneapolis Veterans Affairs Medical Center
name: Ronald R Bach, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.