Scientific objective and rationale: Gulf War veterans report more complaints of chronic fatigue, pain, and concentration difficulties compared to others who have served in the military. These symptoms are similar in nature to symptoms of chronic fatigue syndrome (CFS), another unexplained medical condition. Mitochondrial dysfunction (an inability of cells to produce adequate energy) is considered to be a cause of CFS and may also be one of the contributing factors to GWI. Therefore, it is highly likely that a treatment already shown to provide improvement to the fatigue and concentration disturbances associated with CFS may in fact be able to produce a similar level of improvement in patients with GWI. The proposed treatment (a currently available medication used to treat Attention Deficit Disorder co-administered with a highly potent nutritional supplement that supports cellular energy production) has been previously studied in a small number of patients with CFS. When given to people with CFS, noticeable improvement in fatigue and concentration occurred within 4 weeks of starting the medication, and this improvement continued for the 12-week duration of the study. The proposed study will provide this same treatment for 12 weeks to patients with GWI. If symptoms are improved, these medications could provide a readily available treatment for many veterans suffering from GWI.

Ultimate applicability of the research: If the proposed study finds that the combination of a currently available medication (generic Ritalin®) plus a highly potent nutritional supplement improves symptoms in GWI veterans, then a larger double-blind, placebo-controlled trial would be performed to generate statistically significant data. This would be the logical next step in the development of an FDA-approved treatment for GWI. Because both components of this treatment are currently available and FDA-approved, the development of a treatment for GWI veterans could be greatly accelerated and available within just a few years.

Types of patients it will help and how will it help them: Two of the symptoms that frequently cause distress and disability in GWI patients are fatigue (61%) and problems concentrating (34%). These symptoms have a profound effect on a GWI patient's ability to function and on their quality of life. For instance, severe fatigue can limit a person's ability to carry on normal daily activities and continue working. Decreased alertness and concentration prevent patients from thinking clearly, handling their finances, remembering important dates, and participating fully in life. Based on preliminary data from the CFS study described above, we expect that GWI veterans, who have many of the same symptoms as people with CFS will see a decrease in their fatigue, alertness problems, and concentration disturbances by approximately 30% to 40% while taking the study treatment.

Potential clinical applications, benefits, and risks: The benefits of this study would be an improvement in GWI patient symptoms (fatigue, alertness problems, and concentration disturbances) during the study period. It is highly likely that a treatment already shown to provide improvement in the fatigue and concentration disturbances associated with CFS may in fact be able to produce a similar level of improvement in patients with GWI. The primary risk associated with this study is that the study participants would not receive any benefit by taking the study treatment. In addition, there are some potential side effects from taking methylphenidate that may include, but are not limited to, headache, anxiety, and changes in blood pressure. There are no known side effects associated with the nutritional supplement when taken at the prescribed dosage.

Projected time it may take to achieve a patient-related outcome: Based on our experience with this treatment in CFS, study patients may experience improvement in their symptoms within a few days to a few weeks of starting the treatment and continue to experience improved well-being for the 12-week duration of the study. We expect it will take approximately 6 months to enroll all study patients and 18 months to complete all the aspects of this trial. If the results are positive, since both components of the study treatment are currently available, a safe and effective treatment for GWI veterans could become available within the next few years.

Likely contributions of this study in advancing a treatment for GWI: This study is designed to provide clear evidence of whether the treatment will decrease specific symptoms in GWI patients and improve certain blood test results that could be used in designing a next phase, larger trial. Should the proposed treatment demonstrate a positive effect on GWI symptoms and demonstrate improved cellular functioning utilizing the lab tests we propose, this would be an important advancement toward developing a treatment for GWI.