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

Ronald R Bach, Rebecca R Rudquist, Ronald R Bach, Rebecca R Rudquist

Abstract

Background: 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.

Objectives: 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.

Rct design and methods: 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.

Results: 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.

Conclusions: 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.

Conflict of interest statement

The authors have declared that no competing interests exist

Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Figures

Fig 1. Consort flow diagram.
Fig 1. Consort flow diagram.
Fig 2. Linear correlation between baseline KSS…
Fig 2. Linear correlation between baseline KSS and baseline PCS.

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