Patients suffering with Gulf War Illness (GWI) are negatively impacted by a myriad of symptoms that vary among patients and include tiredness, headaches, stomach issues, and loss of memory and reasoning. These symptoms may be of sufficient severity that they interfere with daily functioning and quality of life. Other symptoms include muscle pain, respiratory problems, and skin conditions. Currently, treatment is focused on ameliorating symptoms, as the cause and persistence of this chronic condition is poorly understood, despite researchers gaining insight into some potential mechanisms of disease activity. Clinical and basic science studies have shown that disturbances in energy production and immune function play a key role in disease progression. Therefore, the overall goal of the clinical trials outlined in this Consortium is to target treatment more effectively to improve outcomes and quality of life for those suffering with GWI.
Over the last 4 years, Dr. Klimas and her research team as well as Dr. Sullivan and her research team through their respective, previously funded GWI Consortia (GWIC) have identified markers of disease activity including but not limited to energy production, immune function, and inflammation. In addition, both research teams understand that GWI is a complex disease state comprising of contributions from different systems within the body, which is why they aim to collaborate within this proposed Consortium. Their research suggests that treatment will rely on combination approaches that have synergistic effects and/or single drugs with multiple mechanisms of action. In addition, due to the myriad of symptoms tied to GWI that vary among patients, treatments may be effective only for particular subsets of patients, which is why the clinical trials designed in this Consortium focus on similar targets of disease activity from different, well thought-out and validated approaches.
The studies proposed in this Consortium build on the findings from Dr. Klimas and Dr. Sullivan’s previously funded Consortia. There will be three Phase I clinical trials proposed, as well as two Phase II trials, that target mechanisms of energy production, inflammation, and immune function. Specifically, based on findings from Dr. Klimas’s GWIC, Study 1 and Study 2 will evaluate a combination approach that targets inflammation and energy production using entanercept, an injectable drug that has been used in Rheumatoid Arthritis and Psoriasis, and mifepristone, a synthetic steroid. Study 3 and 4 will be based on the findings from Dr. Sullivan’s GWIC and will determine the most effective antioxidant, CoQ10 or glutathione, in a Phase I study and then take the most effective antioxidant and combine it with intranasal insulin. Lastly, Study 5 will evaluate a nutraceutical, Bacopa, that has been shown to have multiple impacts on inflammation, immune function, and energy production. In addition, the clinical trials that are proposed in this Consortium allow testing and improvement as they are implemented. It is the responsibility of this Consortium to be responsive to new knowledge quickly, and not restrict the research efforts of this Consortium to the studies highlighted in this proposal. Thus, this Consortium will have a process in place to provide new research ideas with appropriate review, to set the priorities of the clinical trials group within the funding limits of this Consortium. The Consortium will use this structure to support additional studies through Congressionally Directed Medical Research Programs (CDMRP), Department of Veteran’s Affairs (VA), foundation, and pharmaceutical funding mechanisms. The infrastructure established in this proposal will facilitate a rapid and effective pathway for moving studies from Phase I to Phase III.
It is a key objective of this Consortium to quickly deliver treatments to patients suffering from this debilitating illness. Based on our early experiences with combination synergistic approaches, as well as single drugs with multiple mechanisms of action, we truly believe that the targets in this proposal will help to improve energy production, restore immune function, and reduce inflammation. They will provide a more targeted approach to improve patient outcomes, halt disease progression, and reset dysfunction tied to the disease, at least in a subset, if not in all, patients with GWI.