Intranasal Insulin: A Novel Treatment for Gulf War Multisymptom Illness

Following their deployment to the 1991 Gulf War, many veterans (GWV) reported a constellation
of unexplained health symptoms; common among them were attention and memory difficulties,
fatigue, joint pain, headaches, gastrointestinal complaints, and mood and sleep problems.
Despite the passage of time, the symptom complex persists for many veterans. Indeed, it is
estimated that at least 25 percent of GWV (nearly 170,000 veterans) have a persistent form of
chronic multisymptom illness (CMI). GW deployed veterans are also developing significantly
more chronic diseases such as diabetes, hypertension, arthritis, and coronary heart disease
than their non-deployed veteran peers putting these individuals at risk for accelerated
aging-related diseases of the peripheral and central nervous system (CNS). Recent studies
have shown a slowing of response speed that affects mental flexibility across multiple
cognitive domains (memory, attention, visuospatial functions) especially on tests that were
timed and computerized and where small differences in cognitive reaction times could be
measured. Recent studies also have suggested that the response inhibition deficits shown in
GWV may reflect executive system dysfunction as reflected by slower motor responses across
multiple cognitive domains.

To date, there are no treatments that have been shown to improve the health or cognitive
difficulties of GW veterans; thus there is an urgent need to establish effective, safe, and
tolerable treatments for GW CMI. Previous studies in other cognitive disorders have found
that intranasal insulin improves memory, attention, and mood, reduces neuroinflammation, and
modulates cortisol levels; it has also been identified as a treatment that has the capacity
to alter many of the leading problems of GW CMI.

During this study there are 2 treatment groups and a placebo group that will last for 8
weeks. The treatment groups will self-administer their designated dosage of insulin through a
nasal pump twice a day, while the placebo group will administer saline through a nasal pump
twice a day. These doses have been shown to be effective and safe. The primary outcome
measure will assess improvements in verbal delayed memory using a specific list learning task
and on a measure of selective attention. The study will assess improvements in overall
physical health and mood by asking the participants to complete self report questionnaires.
Neuroendocrine measures will also be obtained in order to evaluate changes in glucose,
insulin, and cortisol levels and examine their impact on GW CMI.

Intranasal insulin has shown great promise in improving memory, attention, and mood in both
older adults with cognitive impairment as well as normal subjects. Thus, this proposal could
prove intranasal insulin to be an effective, safe, and affordable therapy for these ailing
veterans.