Do Antipsychotics Block Insulin Action in the Brain: is it a Class Effect?

ConditionsBrain Insulin Sensitivity Healthy Controls Cognition

Trial statusRecruiting

Trial phasePhase 4

Trial typeInterventional

Biological sexAll

Age18-35

SponsorCentre for Addiction and Mental Health

About this trial

This study aimed at helping researchers understand how a medication called haloperidol can affect insulin action in the brain. Insulin is a hormone in the body that controls sugar levels in part by lowering the amount of glucose produced by the liver. After eating a meal, insulin levels go up in both the blood and the brain. Insulin in the brain has also been shown to affect the way the brain works and processes information (also known as "cognition"). Haloperidol, is an antipsychotic medication used to treat a variety of disorders such as schizophrenia spectrum disorders, bipolar disorder, and major depressive disorder, but long-term use can have metabolic side effects, like weight gain, type 2 diabetes, and cardiovascular disease. The purpose of this study is to investigate how antipsychotic medications, such as haloperidol, which carries the risk of metabolic changes, might interrupt the effect of insulin action in the brain. This will help researchers learn how to potentially reduce metabolic risk for people who take these kinds of medications in the future.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Must be deemed to have the capacity to provide informed consent

Must sign and date the informed consent form

Stated willingness to comply with all study procedures;

Age: 18-35

Disqualifiers

History of psychiatric illness, including any substance use (screened using the Mini International Neuropsychiatric Interview (MINI))

Pre-diabetes or diabetes (fasting glucose ≥6.0 mmol/L, HbA1c>6% or use of anti-diabetic drug),

Evidence of impaired insulin sensitivity, assessed using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥2.5

Family history of diabetes in a first degree relative (parent or sibling)

Trial design

Design model

Crossover

Treatments tested in this trial

Haloperidol
Drug
The oral investigational agent haloperidol (Generic Brand: TEVA-HALOPERIDOL) will be self-administered, at night, over 7 days. Haloperidol will be titrated up to 2 mg.
Placebo
Drug
Oral placebo, encapsulated and to be taken at an equivalent titration schedule to Haloperidol.
Insulin Lispro
Drug
A total of 160 IU of intransal insulin (=1.6 mL) will be administered on MRI scanning visits (80 IU = 0.8 mL delivered per nostril). Humalog; Eli Lilly Canada
Saline
Other intervention
A total of 1.6 mL of intranasal saline will be administered on each MRI scanning visit (0.8 mL delivered per nostril).

Treatment groups

35 Participants

are divided into 2 treatment groups

Group A: HaloperidolExperimental treatment 3 interventions

Group B: PlaceboPlacebo comparator 3 interventions

Trial outcomes

Primary outcomes

RsFC between the anterior cingulate cortex of the salience network and the lateral parietal cortex of the DMN

Resting state functional connectivity (rsFC) between the anterior cingulate cortex of the salience network and the lateral parietal cortex of the default mode network (DMN) will be assessed through a MRI-based assay. Calculated using the correlation between two brain regions' blood-oxygen-level-dependent (BOLD) signal times.

Time frame