Intranasal Insulin and Olanzapine Study in Healthy Volunteers (NCT03741478)
🩺 Plain-English Summary (8th-Grade Level)
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.
Who can join: To join this study, participants generally need to meet the listed inclusion criteria (2 items) and avoid the listed exclusions (12 items).
Location: University Health Network - Toronto General Hospital — Toronto, Ontario
📋 "Do I Qualify?" — 1-Minute Self Screener
Instant ChecklistCheck every box below. If you can check all of them, you may meet the study's basic screening requirements (final eligibility is confirmed by the site team).
Usually NOT eligible if any of the following apply:
- Exclusion Criteria:
- History of current or past psychiatric illness (according to the Mini International Neuropsychiatric Interview \[MINI\]).\[As an exception for the Metabolic Arm only, anxiety disorders will not be exclusionary (including, but not limited to: agoraphobia, social anxiety disorder, generalized anxiety disorder, and panic disorder)\].
- Left-handedness (only for the cognitive and MRI arm)
- Pre-diabetes or diabetes (fasting glucose ≥6.0mmol/L or use of anti-diabetic drug);
- Evidence of impaired glucose tolerance on screening OGTT
- Family history of diabetes
- Use of weight reducing agents or other medications based on the discretion of the PI
- History of liver disease or AST\> 2 times upper limit of normal
- History of kidney disease
- Major medical or surgical event within the last 6 months
- Any condition that interferes with safe acquisition of MRI data such as metal implants, pacemakers, cochlear implants, claustrophobia, etc. (only for the cognitive and MRI component)
- Pregnancy and/or breastfeeding
🔍 Extracted verbatim from the official NIH eligibility criteria. Always confirm with the study coordinator.
📍 All Participating Trial Locations (2 Sites)
- University Health Network - Toronto General Hospital — Toronto, Ontario
- Center for Addiction and Mental Health — Toronto, Ontario
💰 Cost, Insurance & Patient Rights
- 100% Free Items: The investigational treatment and protocol-required procedures are supplied at zero cost by the sponsor.
- Routine Patient Care: Under federal law (ACA § 2709) and many state statutes, routine care costs are covered during participation.
- Voluntary Participation: You may withdraw at any time without affecting your standard medical care.