Ketamine in Veterans With Gulf War Illness

Recruitment for this study starts after protocol approval by the BCM IRB, MEDVAMC R\&D, and DoD HRPO. All study procedures are for research only.

Potential subjects will be recruited (i) from the Houston community with advertisements in local papers and social media, and with flyers at BCM and MEDVAMC; (ii) among veterans from the 1990-1991 Gulf War who participated in protocol H-40948 and who consented to be recontacted for future studies; (iii) among veterans from the 1990-1991 Gulf War who voluntarily registered in the Gulf War Registry (GWR) because of concerns of possible Gulf War Illness (GWI). Individuals under category (i) will contact us. Individuals under category (ii) will be contacted by phone or text. Individuals under category (iii) will be contacted by letter and, after a 10-day non-response, by phone. Before sending a letter, names in the GWR will be matched with those in CPRS. If in CRPS, medical information will be reviewed to determine study eligibility; if apparently eligible, the letter will be send. If an individual is not in CPRS, the letter will be send. The letter is uploaded in section S.

For the phone call, after providing verbal consent, veterans who are interested in the study, and who did not participate in protocol H-40948, will undergo an in-depth phone pre-screen to determine eligibility. The phone pre-screen inventories symptoms of Gulf War Illness and military history with the Gulf War Military and Health Questionnaire.

This study consists of 3 phases: screening, infusion of ketamine, telephone follow-up.

For phase 1, eligible subjects will provide a urine sample for drug and pregnancy testing, undergo blood pressure testing, will undergo an EKG, will have to provide a 20 ml (2 tsp) blood sample collected for clinical labs (an additional 10 ml (2 tsp) is optional and will be banked for future research), and will visit with a study physician for a medical examination. Finally, we will go over the Gulf War Military and Health Questionnaire assessed during the phone-screen. Total time of phase 1 is 4 to 5 hours.

If qualified for the study, subjects will be scheduled for phase 2: the administration of a single intravenous infusion of 0.5 mg/kg of ketamine. For phase 2, veterans will need to fast for at least 8 hours before the infusion; they can take their medications as prescribed. At arrival at the study site, subjects have to provide a urine sample for drug and pregnancy testing. We will go over their medical information collected in phase 1 to inventory changes, and they will undergo testing of vital signs. Before the infusion at 10 am, subjects will be asked to fill out Gulf War Military and Health Questionnaire (24 hours symptoms). A baseline of possible side effects is established with the CADSS which assess dissociative states. Finally, EEG is collected from the scalp using 4-minute resting EEG (eyes-open/eyes-closed) and 15-minute passive computer paradigm with auditory 85-dB click trains. The infusion of 0.5 mg/kg ketamine is prepared by the MEDVAMC Research Pharmacy. Ketamine is dissolved in 0.9% saline in a bag of saline with a total volume of 100 mL, and administered with an infusion pump at a constant rate. An anesthesiologist will place an indwelling catheter. We will first collect an 10 ml (2 tsp) sample of blood for pro-inflammatory cytokine. Next, the catheter is used for the infusion, which lasts 40 minutes. The EEG and blood collection is repeated at 35-minutes (the peak of ketamine concentration), and again one and two hours later. Subjects will not be discharged before four hours after the end of the infusion.

For phase 3, as part of the research procedures, subjects will be contacted by telephone or telehealth services at a pre-arranged time of mutual convenience on days 1, 2 and 7 after the infusion to inventory 24-hr symptoms with the Gulf War Military and Health Questionnaire. This procedure lasts about 45 minutes to complete