Gulf War (GW) Veterans continue to experience chronic health symptoms often called GW Illness (GWI) that impact fatigue, musculoskeletal function, mood, and cognition. Cognitive symptoms include poor attention/concentration and memory function and have proven to be some of the most troubling symptoms for ill GW Veterans. There are no current treatments that have been shown to substantially improve cognitive functioning or other chronic health symptoms of GW Veterans, and therefore there is an urgent need to identify effective and safe treatments for GWI. Previous studies in other cognitive disorders have found that treatment using d-cycloserine (DCS) medication can both improve memory, attention, and mood and can enhance the cognitive improvements when paired with cognitive-behavioral therapy by improving the memory pathways activated during new learning. DCS has also been shown to reduce neuroinflammation, regulate glutamate levels, and improve memory circuitry in the brain by improving synaptic functions in the hippocampus. DCS has a good safety record and is currently approved by the Food and Drug Administration (FDA) for the treatment of tuberculosis.

Chronic neuroinflammation is being studied as the mechanism for the chronic health problems of GW Veterans by Drs. Sullivan, Toomey, and other GWI investigators in a Gulf War Illness Research Program-funded consortium study called the "Gulf War Illness Consortium" (GWIC). The GWIC will provide the study participants for the currently proposed pilot clinical treatment trial for GWI that will now partner with a leading Boston area expert in the use of DCS in conjunction with cognitive behavioral therapy to facilitate treatment of a variety of anxiety disorders.

This treatment trial can make an important contribution because it seeks to evaluate a treatment for memory and attention, overall physical health and mood in GWI. It also seeks to compare symptoms common to GWI including fatigue, pain, sleep quality, and self-reported cognitive functioning. We predict that DCS will improve memory, attention, physical health, and mood as well as other symptoms common to GWI.

This study is a straightforward pilot study comparing a DCS treatment group and a placebo group for 4 weeks. The treatment groups will self-administer the DCS or placebo (sugar pill) capsules once per day. The dose has been shown to be effective and safe in cognitively impaired elderly and younger normal groups, as well as in a number of clinical samples. Several tests will be used to measure the effective of the DCS therapy. The primary outcome measures will be specific tests of verbal memory testing of word-pairs and tests of computerized focused or sustained attention and a test of more selective attention. Other outcomes will include self-report questionnaires of physical health and mood.

This GWI treatment study will bring leading GWI experts together with a leading expert in using DCS as a cognitive enhancer in another clinical disorder to identify a safe and effective treatment for ill GW Veterans. DCS is an FDA-approved therapy that has been shown to improve cognitive functioning and alter many of the leading areas thought to be associated with the physical causes of GWI including reducing neuroinflammation, normalizing glutamate levels, and improving hippocampal memory functions. This could result in significant improvements in memory and attention abilities and mood in GW Veterans with GWI. Providing Veterans even moderate relief from these chronic and debilitating symptoms could have a tremendous impact on improving their overall sense of well-being and quality of life. DCS could prove to be a safe and effective new treatment for ailing GW Veterans.