Subgroup analysis of MCS changes from baseline.

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.

研究背景
海湾战争综合征（Gulf War Illness, GWI）是一类与军事部署相关的慢性多症状疾病，严重影响1990至1991年海湾战争退伍美军的健康相关生活质量（Health-related Quality of Life, HRQOL）。本团队在针对GWI的初始研究中，发现了一类促炎性血液生物标志物特征，由此提出假说：慢性炎症是GWI病理生理学机制的组成部分。

研究目标
本项二期随机对照试验（Phase 2 Randomized Controlled Trial, RCT）旨在验证GWI炎症假说，通过评估抗炎药物与安慰剂对GWI退伍军人健康相关生活质量的影响开展研究。本试验已在ClinicalTrials.gov平台完成注册，登记号为NCT02506192。

随机对照试验设计与方法
符合堪萨斯GWI病例判定标准的海湾战争退伍军人被随机分配接受10mg缓释泼尼松或匹配安慰剂。本研究采用退伍军人兰德36项健康调查（Veterans RAND 36-Item Health Survey）评估受试者的健康相关生活质量。主要结局指标为躯体成分总结（Physical Component Summary, PCS）评分相较于基线的变化值，该评分用于衡量躯体功能与症状水平；PCS评分升高提示躯体健康相关生活质量得到改善。

研究结果
对于基线PCS评分低于40的受试者，服用缓释泼尼松8周后，其平均PCS评分从基线的32.9±6.0升高15.2%至37.9±9.0。配对t检验分析显示，该评分变化具有统计学显著性（p=0.004）。而在停药8周后，受试者的平均PCS评分回落至32.7±5.8。

研究结论
泼尼松相关的躯体健康相关生活质量改善，为GWI炎症假说提供了支持证据。明确泼尼松用于治疗GWI的临床疗效，需开展三期随机对照试验。