Up to one third of the 700,000 U.S. military veterans of the 1990-91 Gulf War have Gulf War
Illness (GWI), a symptom complex characterized by a combination of chronic pain, cognitive
impairment, debilitating fatigue, gastrointestinal complications, and other persistent
symptoms. Epidemiologic studies of 1990-1991 Gulf War veterans have identified the short but
intense combined exposure to insecticides (e.g., organophosphates, DEET, permethrin), pills
with anti-nerve gas agent pyridostigmine bromide (PB), and low-level chemical nerve agents as
likely candidates of GWI. Animal models have shown that these neurotoxicants could induce
neuroinflammation which is marked by enhanced inflammatory cytokines, and activated microglia
and astrocytes. Inflammation has been linked to GWI. Secondary effects of neuroinflammation
and glia activation could be excessive glutamate-mediated neuronal activation. There is
currently no treatment for symptoms of GWI. Ketamine is an N-methyl-D-aspartate receptor
(NMDAR) antagonist. Besides blocking activation of NMDARs, a sub-anesthetic dose (0.5 mg/kg
over 40 minutes) of ketamine could be an anti-inflammatory agent, and could protect microglia
and astrocytes from being activated by inflammatory agents. This low dose of ketamine has
also been shown to improve fatigue within 24 hours after a single infusion, and to improve
inflammatory pain. This makes ketamine a feasible candidate for the treatment of
inflammation-associated symptoms of GWI. This pilot study will examine if GWI is related to
NMDAR functioning, testing effects of a single 40-minute intravenous infusion of 0.5 mg/kg of
ketamine on GWI symptom severity in 21 veterans of the 1990-1991 Gulf War who meet Kansas
case definition criteria of GWI.
Phase:
Early Phase 1
Details
Lead Sponsor:
Baylor College of Medicine
Collaborators:
Michael Debakey Veterans Affairs Medical Center Michael E. DeBakey VA Medical Center