Gulf war illness inflammation reduction trial: A phase 2 randomized controlled trial of low-dose prednisone chronotherapy, effects on health-related quality of life

• Published in: PloS one Vol. 18; no. 6; p. e0286817
• Main Authors: Bach, Ronald R., Rudquist, Rebecca R.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.06.2023; Public Library of Science (PLoS)
• Subjects: Alcohol; Analysis; Anti-inflammatory agents; Biology and Life Sciences; Biomarkers; Cardiovascular disease; Chronotherapy; Circadian rhythm; Clinical trials; Cognitive ability; Complications and side effects; Corticosteroids; Diseases; Dosage and administration; Drug dosages; Fatigue; Gulf War; Gulf War syndrome; Health; Health aspects; Hemoglobin; Hospitalization; Humans; Hypotheses; Illnesses; Inflammation; Inflammation - drug therapy; Inflammatory bowel disease; Liver diseases; Medicine and Health Sciences; Military; Military personnel; Pathophysiology; Patient outcomes; Persian Gulf Syndrome - drug therapy; Persian Gulf War; Persian Gulf War veterans; Placebos; Prednisone; Prednisone - therapeutic use; Product development; Quality of life; Questionnaires; R&D; Research & development; Research and Analysis Methods; Rheumatoid arthritis; Social Sciences; Statistical analysis; Uranium; Veterans; War; United States; Kansas; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0286817

Gulf War illness (GWI) is a deployment-related chronic multisymptom illness impacting the health-related quality of life (HRQOL) of many U.S. Military Veterans of the 1990-91 Gulf War. A proinflammatory blood biomarker fingerprint was discovered in our initial study of GWI. This led to the hypothesis that chronic inflammation is a component of GWI pathophysiology. The GWI inflammation hypothesis was tested in this Phase 2 randomized controlled trial (RCT) by measuring the effects of an anti-inflammatory drug and placebo on the HRQOL of Veterans with GWI. The trial is registered at ClinicalTrials.gov, Identifier: NCT02506192. Gulf War Veterans meeting the Kansas case definition for GWI were randomized to receive either 10 mg modified-release prednisone or matching placebo. The Veterans RAND 36-Item Health Survey was used to assess HRQOL. The primary outcome was a change from baseline in the physical component summary (PCS) score, a measure of physical functioning and symptoms. A PCS increase indicates improved physical HRQOL. For subjects with a baseline PCS <40, there was a 15.2% increase in the mean PCS score from 32.9±6.0 at baseline to 37.9±9.0 after 8 weeks on modified-release prednisone. Paired t-test analysis determined the change was statistically significant (p = 0.004). Eight weeks after cessation of the treatment, the mean PCS score declined to 32.7±5.8. The prednisone-associated improvement in physical HRQOL supports the GWI inflammation hypothesis. Determining the efficacy of prednisone as a treatment for GWI will require a Phase 3 RCT.