Gulf War Illness

Background: Gulf War illness (GWI) affects up to 210,000 U.S. veterans who served in the Middle East during the Gulf War in 1990-1991. Symptoms include fatigue, muscle and joint pain, forgetfulness, headaches, rashes, and sleep disturbances. Routine exams cannot determine the cause of GWI. Researchers need more information to understand this disease. Objective: This natural history study will look for differences in Gulf War veterans who experienced GWI and those who did not. Eligibility: Gulf War veterans with GWI. Healthy Gulf War veterans who do not have GWI are also needed. Design: Participants will stay in the NIH Clinical Center as an inpatient for 2 weeks. They will undergo many tests. Blood will be drawn many times throughout the study. Participants will also give urine, saliva, and stool samples. Scans to measure the brain, leg muscles, bone density and body mass will be done. They will have an exercise stress test and muscle strength tests. They will have a sleep study. They will have tests to look at how well the brain, heart and lungs are working. Participants will sleep in a specialized room that measures the amount of oxygen they use and the carbon dioxide they produce on four consecutive nights. A sample of fluid will be collected from inside the spine. Participants will take many surveys. Some will ask about their activities. Some will be about emotional and mental health. Some will be about thinking, memory, and behavior. Optional tests include other imaging scans and testing the autonomic nervous system. Samples of skin and muscle may be taken. After discharge, participants will wear activity monitors for 14 days. They will keep a diary of their symptoms, including fatigue, pain, and sleep, while wearing the monitors.

Gulf War Illness (GWI) affects an estimated 25-32% of the over 700,000 coalition troops deployed to the Persian Gulf as part of the First Gulf War. GWI causes a range of pain, fatigue, gastrointestinal, skin, neurologic, and respiratory symptoms. New treatments to reduce GWI-associated morbidity are critically needed. Research suggests a role for the gastrointestinal microbiome in mediating health, including through impacting metabolism and immunity. The disruption of this microbiome plays a role in multiple diseases, and preliminary data suggest that Veterans with GWI have altered gut microbiota. The investigators will evaluate the effectiveness of a dietary fiber prebiotic supplement intervention on improving the quality of life of Veterans with GWI.

The goal of this clinical trial is to create a machine learning algorithm to improve active repetitive transcranial magnetic stimulation (rTMS) treatments for veterans and/or active military personnel by alleviating Gulf War Illness related headaches and body pain (GWI-HAP). This study aims to develop and validate a Support Vector Machine (SVM) model that could replace the trial-and-error process by assessing functional connectivity provided by resting state functional magnetic resonance imaging (rs-fMRI) data to predict the most effective rTMS protocol for each person. All participants will be receiving active rTMS treatment. The main questions it intends to answer are: 1. Does the SVM model predict a more effective treatment response rate for predicted respondents undergoing active rTMS at the left dorsolateral prefrontal cortex (DLPFC) compared to predicted non-respondents? 2. Does the SVM model predict a more effective treatment response rate while undergoing active rTMS at the left dorsolateral prefrontal cortex (DLPFC) and left motor cortex (LMC) in predicted respondents compared to predicted non-respondents? Participants will undergo the following: 1. Receive a total of 13 active rTMS treatment sessions over 3-4 months. 2. Visit the clinic for a total of 15 visits for assessments, check ups, and treatments. 3. Keep a daily log of their headaches, muscle and joint pain throughout the study.

Many veterans with Gulf War Illness developed chronic gastrointestinal symptoms during their deployment to the Persian Gulf. The pathophysiologic mechanisms of these chronic gastrointestinal symptoms are not well understood but cause significant morbidity in veterans. Our proposed studies will provide an innovative and novel treatment trial for chronic gastrointestinal symptoms in veterans with Gulf War Illness that were deployed into war zones. Given that there are currently no specific treatments for these disorders, and that current symptomatic approaches are far from ideal, proof of principle of our trial would be an extremely important advance as it would not only have a beneficial impact on the health of many thousands of our veterans, but also it would substantially reduce the many negative economic effects of this ailment on the VA Health Care System.

The primary objective of this clinical trial is to determine if treatment with Butyrate formulation that consists of butyric acid as calcium and magnesium derivatives (Ca-Mg Butyrate) improves the physical function of men and women Veterans suffering from Gulf War Illness (GWI). The primary outcome measure is a change from baseline on the Short Form Health Survey 36-item (VSF-36), with respect to physical functioning and symptoms. The secondary outcome will focus on the drug's role in (a) restoring gut microbiome and virome, (b) decreasing gastrointestinal disturbances (constipation, diarrhea, pain), (c) decreasing chronic fatigue, (d) decreasing systemic inflammation, and (e) a decrease in cognitive deficits.

The investigators goals are to identify blood lipids/metabolites that correlate with cognitive decline in the presence of the APOE ε4 allele among veterans with GWI. To determine the effect of dietary, medical and biological factors that influence lipid and metabolites in blood from GW veterans. To identify blood lipid/metabolite profiles that correlate with bioenergetics deficits and glial activation in the brains of GWI. To validate blood biomarker signatures of GWI using APOE genotyping and blood lipids/metabolites that correlate with the CNS dysfunction in GWI.

In this multi-site trial, we will use a randomized, double-blind, placebo-controlled study design to test whether 300 mg of Nicotinamide Riboside (NR) can achieve the primary objective of increasing plasma NAD+ levels in participants with Gulf War Illness (GWI).

Gulf War Illness is a condition that affects multiple major organ systems, resulting in a diverse array of symptoms that include debilitating fatigue, memory and cognition difficulties, headaches, sleep disturbances, gastrointestinal problems, skin rashes, and musculoskeletal/joint pain. This phase II, double masked, randomized, placebo-controlled, two-arm study will evaluate cognitive function as evidence of efficacy of the nutraceutical intervention, Bacopa, on central nervous system symptom management of Gulf War Illness, along with assessments of safety of the intervention.

This clinical trial aims to confirm previous findings from a smaller study which demonstrated significant improvements in all symptoms among veterans with Gulf War Illness after one month on the dietary intervention. The main objectives of this study are: 1) to confirm previous findings of treatment response to the diet in a larger and more diverse group; 2) to examine how changes in the nervous system may be the reason for improvement; and 3) to identify markers which change in the blood after one month on the diet. Participants will have baseline measures collected and then will be randomized into the intervention or wait-listed control group, which they will follow for one month before being reassessed.