Intranasal Insulin and Olanzapine Study in Healthy Volunteers
Status:
Recruiting
Trial end date:
2022-09-30
Target enrollment:
Participant gender:
Summary
Antipsychotic (AP) medications are considered to be the gold standard treatment for psychotic
disorders including schizophrenia. However, APs have also been commonly associated with
serious metabolic adverse effects including weight gain and Type 2 Diabetes, with younger
populations disproportionately affected. In addition, young individuals treated with these
agents have also been found to be at high risk for glucose dysregulation, including higher
rates of prediabetes, with significant associations found between AP use and insulin
resistance. Due to the concerning prevalence of these AP metabolic effects, it becomes
important to further elucidate the mechanisms underlying AP effects on glucose metabolism,
which are still poorly understood. One potential underlying mechanism is insulin which has
been found to regulate hepatic (liver) glucose production through insulin receptors in the
brain. These insulin receptors also play a role in neuronal growth and memory, or more
broadly, cognition. Preliminary data in rat models has demonstrated that the AP olanzapine
(OLA) inhibits the ability of a central insulin stimulus (acting at the level of the brain)
to decrease endogenous glucose production (EGP), making this mechanism a prime target to
translate from rodent models to human research. Furthermore, intranasal insulin (INI)
administration (an analogous central insulin stimulus) has been repeatedly associated with
improved cognitive performance for verbal memory and visuospatial functions in humans. Given
these findings and with the goal of translational research, the present study will
investigate OLA's effects in healthy human volunteers including: (a) the ability of INI to
reduce EGP during a pancreatic euglycemic clamp (PEC; a glucose metabolism and insulin
procedure); and (b) the ability of INI to improve cognitive performance. More specifically,
the present study hypothesizes that:
1. INI will be associated with a decrease in EGP relative to intranasal placebo (INP) as
measured by the PEC. This effect will be inhibited if OLA is co-administered.
2. OLA administration will be associated with decrements in cognitive measures (i.e.,
visuospatial, and verbal memory) as compared to placebo (PL). Additionally, OLA
co-administration will block the beneficial effects of INI on cognition previously
supported by other studies.
3. INI will result in adaptive changes in neurochemical and neurohemodynamic measures as
studied using MRI imaging techniques.