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| Name | Class |
|---|---|
| The Physicians' Services Incorporated Foundation | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Haloperidol | Experimental | 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. |
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| Placebo | Placebo Comparator | Placebo capsules, visually identical to those containing haloperidol, will be administered according to the same dosing schedule |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From enrollment to the end of study will be up to 5 months |
| Metabolic Outcome: BMI | Weight (kg) and Height (cm) will be aggregated to BMI (kg/m^2) at screening and MRI scanning visits. | From enrollment to the end of study will be up to 5 months |
| Metabolic Outcome: Waist Circumference | Waist Circumference (cm) collected at screening and MRI scanning visits. | From enrollment to the end of study will be up to 5 months |
| Metabolic Outcome: Glucose | Glucose (mmol/L), will be measured at 2 time points on each MRI scanning day, pre- and post-intranasal insulin challenge. | From enrollment to the end of study will be up to 5 months |
| Metabolic Outcome: Insulin | Insulin (uIU/mL), will be measured at screening and at 2 time points on each MRI scanning day, pre- and post-intranasal insulin challenge. | From enrollment to the end of study will be up to 5 months |
| Metabolic Outcome: C-peptide | C-peptide (nmol/L), will be measured at screening and 2 time points on each MRI scanning day, pre- and post-intranasal insulin challenge. |
| Measure | Description | Time Frame |
|---|---|---|
| Antipsychotic Related Outcome: Plasma antipsychotic (haloperidol) level | Plasma antipsychotic (haloperidol) levels will be measured with concentrations expressed in nanograms per millilitre (ng/mL). Collected on each MRI scanning day. | From enrollment to the end of study will be up to 5 months |
| Antipsychotic Related Outcome: Stanford Sleepiness Scale |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mahavir Agarwal, MBBS, MD, PhD | Contact | 416-535-8501 | 30546 | mahavir.agarwal@camh.ca |
| Maria Papoulias, MSc | Contact | 416-535-8501 | 39365 | maria.papoulias@camh.ca |
| Name | Affiliation | Role |
|---|---|---|
| Mahavir Agarwal, MBBS, MD, PhD | Centre for Addiction and Mental Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre for Addiction and Mental Health | Recruiting | Toronto | Ontario | M6J 1H3 | Canada |
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| ID | Term |
|---|---|
| D006220 | Haloperidol |
| D061268 | Insulin Lispro |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D002090 | Butyrophenones |
| D007659 | Ketones |
| D009930 | Organic Chemicals |
| D061266 | Insulin, Short-Acting |
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| 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 |
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| Saline | Other | A total of 1.6 mL of intranasal saline will be administered on each MRI scanning visit (0.8 mL delivered per nostril). |
|
| From enrollment to the end of study will be up to 5 months |
| Metabolic Outcome: HbA1c | HbA1c (mmol/mol), will be measured at screening and 2 time points on each MRI scanning day, pre- and post-intranasal insulin challenge | From enrollment to the end of study will be up to 5 months |
| Metabolic Outcome: HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) | HOMA-IR, will be measured at 2 time points on each MRI scanning day, pre- and post-intranasal insulin challenge. HOMA-IR = (Fasting Insulin (uIU/mL) * Fasting Glucose (mmol/L)) / 22.5 | From enrollment to the end of study will be up to 5 months |
The Stanford Sleepiness Scale (SSS), which is a self-reported scale (scale of 1-7), where higher scores indicate greater sedation. Administered on each MRI scanning visit. |
| From enrollment to the end of study will be up to 5 months |
| Antipsychotic Related Outcome: Digit Symbol Substitution Test | The Digit Symbol Substitution Test (DSST), which will be reported as the number of correct responses (count per 90 seconds), where lower scores reflect greater sedation or cognitive slowing. Administered on each MRI scanning day. | From enrollment to the end of study will be up to 5 months |
| Antipsychotic Related Outcome: Barnes Akathisia Scale | The Barnes Akathisia Scale (BAS) (scale of 0-14), with higher scores indicating more severe akathisia. Administered on each MRI scanning day. | From enrollment to the end of study will be up to 5 months |
| Antipsychotic Related Outcome: Simpson-Angus Scale | The Simpson-Angus Scale (SAS) (scale of 0-40), where higher values indicate more pronounced parkinsonian symptoms. Administered on each MRI scanning day. | From enrollment to the end of study will be up to 5 months |
| Antipsychotic Related Outcome: Abnormal Involuntary Movement Scale | Abnormal Involuntary Movement Scale (AIMS) (scale of 0-42), with higher scores corresponding to more severe involuntary movements. Administered on each MRI scanning day. | From enrollment to the end of study will be up to 5 months |
| Antipsychotic Related Outcome: UKU Side Effect Rating Scale | Side effects will be assessed using the UKU Side Effect Rating Scale, which will be reported as a scale score (scale of 0-144), where higher scores indicate a greater burden of side effects. Administered on each MRI scanning day. | From enrollment to the end of study will be up to 5 months |
| D061385 |
| Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |