The proposed Phase III study follows a promising Phase I/II double-blind, placebo-controlled crossover study of CoQ10 in 46 veterans with Gulf War illness (GWI) who met both the Kansas and CDC case definitions who were treated with 100mg or 300mg of a high bioavailability CoQ10 (ubiquinone) product or placebo. The study, performed by Dr. Beatrice Golomb and her team at the San Diego VA, found a significant improvement in men with GWI vs. placebo using their selected primary outcome variable, the general self-rated health, in a sex-stratified analysi which showed a response in men with GWI, but less so in the 7 women included in the study. The investigators concluded that CoQ10 conferred benefit to physical function and symptoms in Veterans with GWI and that examination in a larger sample was warranted. Since there is currently little to offer GWI that is evidence based, it is a stated VA research priority to move promising Phase II work to Phase III study; thus, initiating a Phase III treatment trial of CoQ10 a this time is of the utmost importance to providing some relief to ailing GW Veterans. A double-blind, placebo-controlled 4-site trial with 200 Veterans with GWI is proposed with sufficient men and women in the sample to perform sex stratification analyses. The clinical and laboratory testing will be performed without knowledge of the subjects' group membership, drug or placebo condition, and will remain blinded throughout the study until its conclusion. The subject schedule includes 5 on-site assessments which include the screening visit with informed consent, the drug initiation visit, an 8 week visit and 16 and 24 week visits, with collection of blood, saliva, and urine and neurocognitive testing. In addition, there is a web-based self-report assessment given every 4 weeks throughout the treatment period and at 4 weeks after completion of the study drug. Subjects will also utilize an activity monitor device to assess activity and sleep throughout the study period through 7 months. The primary analysis to evaluating the efficacy of CoQ10 in GWI will compare treatment groups on SF-36 physical function score over time in a repeated measures setting using a two-sided 0.05 level of significance. Other clinical efficacy end points will be the self-report assessment measures across the domains of fatigue, pain, sleep, and the SF36 subscales of function and severity. Objective measures will include neurocognitive testing, activity data, and laboratory data that could reasonably be considered a surrogate for illness severity (e.g. measures of immune activation, inflammation, and cell function). In addition to the primary objective (efficacy and safety of ubiquinol in GWI), this stuy will offer a platform for the much needed analysis of outcome variables in a well characterized longitudinal cohort, both biomarkers and clinical measures will be analyzed for their utility in future studies. We will also have developed the framework of a much needed clinical trials group for future studies of GWI. If the study proves efficacy, the clinical trials group will work with the VHA to add ubiquinol to the national formulary and update GWI care guidelines. Research findings will be disseminated to key decision-makers, including both the clinical and research leadership of the VA. The medical, academic, and research communities will be reached directly through traditional means of dissemination through publication in peer-reviewed journals, presentations at national conferences as well as updates to Veteran groups and to policymakers who have an interest in the health of GW Veterans.
The primary objective of this Phase III double-blind, placebo-controlled study is to determine the efficacy and safety of ubiquinol in men and women suffering from Gulf War illness. This study will also offer a platform for the much-needed analysis of outcome variables in a well-characterized longitudinal cohort, both biomarkers and clinical measures will be analyzed for their utility in future studies. In the process, we will also have developed the framework of a much-needed clinical trials group for future studies of GWI.