Brain Insulin SensitivityPhase 4NCT07109245
Do Antipsychotics Block Insulin Action in the Brain: is it a Class Effect?
A Phase 4 study testing Haloperidol, Insulin Lispro and Saline in people with Brain Insulin Sensitivity and Healthy Controls, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Brain Insulin Sensitivity, Healthy Controls, Cognition
- What is being tested?
- Haloperidol, Insulin Lispro and Saline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 1 siteCanada
- Study dates
- 11 Dec 2025to Dec 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
- Body Mass Index (BMI) 18.5-24.9 kg/m2
- Both sexes
Who cannot join
- 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)
- Use of weight reducing agents
- History of kidney or liver disease
Show all 17Show fewer
- History of cell blood disorders
- Irregular menstrual cycles (e.g., menstruation occurs less than 21 days or more than 35 days apart, or not having menstruated for three months (or 90 days), or conditions such as endometriosis or polycystic ovary syndrome (PCOS) or prior surgical interventions such as a hysterectomy or oophorectomy)
- Current use of hormonal birth control (e.g., pill, patch, hormonal intrauterine device [IUD], ring). Participants must have had at least 2 regular menstrual cycles following the discontinuation of hormonal birth control [50]
- Current use of progesterone, estrogen, testosterone, or fertility treatment.
- Pregnant, gave birth in the last year, or breastfeeding. Participants must have at least 3 regular menstrual cycles post-breastfeeding before beginning the study.
- Major medical or surgical event within the last 6 months
- Contraindications for MRI, including metal implants, pacemakers, cochlear implants, claustrophobia, weight >250 lbs
- Any contraindications to the investigational products as listed in the product monographs including known hypersensitivity to the drug or the excipients of the product (note: enzymatic lactose intolerance is NOT exclusionary),
- Any medications that increases risk of hypoglycemia or could contribute to hyperglycemia
- Any medical conditions that constitute as a warning/precaution for haloperidol, lorazepam, benztropine, or insulin.
- Use of any of the prohibited medications listed in the product monograph of haloperidol, lorazepam, benztropine, or insulin (Pheochromocytoma, barbiturates, and narcotics are exclusionary, any use of painkillers and antihistamines must be reviewed by PI but are not exclusionary
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Centre for Addiction and Mental Health
Toronto, Ontario, M6J 1H3
Mahavir Agarwal, MBBS, MD, PhD, 416-535-8501 ext. 30546, mahavir.agarwal@camh.ca
About this study
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.
- Conditions
- Brain Insulin Sensitivity, Healthy Controls, Cognition
- Being tested
- Haloperidol, Placebo, Insulin Lispro, Saline
- Keywords
- Brain Insulin Sensitivity, Healthy Control Study, Haloperidol, Cognition, MRI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HaloperidolDrug
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.
PlaceboDrug
Oral placebo, encapsulated and to be taken at an equivalent titration schedule to Haloperidol.
Insulin LisproDrug
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
SalineOther
A total of 1.6 mL of intranasal saline will be administered on each MRI scanning visit (0.8 mL delivered per nostril).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Haloperidol; Drug: Insulin Lispro; Other: Saline |
| Placebo | Placebo comparator | Placebo capsules, visually identical to those containing haloperidol, will be administered according to the same dosing schedule Receives: Drug: Placebo; Drug: Insulin Lispro; Other: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: From enrollment to the end of study will be up to 5 months
Secondary outcomes (7)
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.
Measured: From enrollment to the end of study will be up to 5 months
Antipsychotic Related Outcome: Stanford Sleepiness Scale
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From enrollment to the end of study will be up to 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2025
- Study start11 Dec 2025
- Primary completionAug 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain Insulin SensitivityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- The Physicians' Services Incorporated Foundation
- Responsible party
- Sponsor
- Investigators
- Mahavir Agarwal, MBBS, MD, PhD, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07109245
- Sponsor's protocol ID
- 2025/010
- Status last verified
- Mar 2026
- First submitted
- 17 Jul 2025
- Last updated
- 2 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Do Antipsychotics Block Insulin Action in the Brain: is it a Class Effect?
- ClinicalTrials.gov ID
- NCT07109245
- Acronym / sponsor ID
- 2025/010
- Conditions
- Brain Insulin Sensitivity, Healthy Controls, Cognition
- Keywords
- Brain Insulin Sensitivity, Healthy Control Study, Haloperidol, Cognition, MRI
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- The Physicians' Services Incorporated Foundation
- Study start
- 11 Dec 2025 (actual)
- Primary completion
- Aug 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 7 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Haloperidol | Experimental | Drug: Haloperidol, Drug: Insulin Lispro, Other: SalineThe 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 | Placebo comparator | Drug: Placebo, Drug: Insulin Lispro, Other: SalinePlacebo capsules, visually identical to those containing haloperidol, will be administered according to the same dosing schedule |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
- Body Mass Index (BMI) 18.5-24.9 kg/m2
Key exclusion criteria (17 listed)
- 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)
- Use of weight reducing agents
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HaloperidolThe 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. | Drug | Haloperidol |
| PlaceboOral placebo, encapsulated and to be taken at an equivalent titration schedule to Haloperidol. | Drug | Placebo |
| Insulin LisproA 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 | Drug | Haloperidol, Placebo |
| SalineA total of 1.6 mL of intranasal saline will be administered on each MRI scanning visit (0.8 mL delivered per nostril). | Other | Haloperidol, Placebo |
Primary outcome
RsFC between the anterior cingulate cortex of the salience network and the lateral parietal cortex of the DMN
Time frame: From enrollment to the end of study will be up to 5 months
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.
Metabolic Outcome: BMI
Time frame: From enrollment to the end of study will be up to 5 months
Weight (kg) and Height (cm) will be aggregated to BMI (kg/m^2) at screening and MRI scanning visits.
Metabolic Outcome: Waist Circumference
Time frame: From enrollment to the end of study will be up to 5 months
Waist Circumference (cm) collected at screening and MRI scanning visits.
Metabolic Outcome: Glucose
Time frame: From enrollment to the end of study will be up to 5 months
Glucose (mmol/L), will be measured at 2 time points on each MRI scanning day, pre- and post-intranasal insulin challenge.
Metabolic Outcome: Insulin
Time frame: From enrollment to the end of study will be up to 5 months
Insulin (uIU/mL), will be measured at screening and at 2 time points on each MRI scanning day, pre- and post-intranasal insulin challenge.
Metabolic Outcome: C-peptide
Time frame: From enrollment to the end of study will be up to 5 months
C-peptide (nmol/L), will be measured at screening and 2 time points on each MRI scanning day, pre- and post-intranasal insulin challenge.
Metabolic Outcome: HbA1c
Time frame: From enrollment to the end of study will be up to 5 months
HbA1c (mmol/mol), will be measured at screening and 2 time points on each MRI scanning day, pre- and post-intranasal insulin challenge
Metabolic Outcome: HOMA-IR (Homeostatic Model Assessment for Insulin Resistance)
Time frame: From enrollment to the end of study will be up to 5 months
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
7 secondary outcomes
Antipsychotic Related Outcome: Plasma antipsychotic (haloperidol) level
Time frame: From enrollment to the end of study will be up to 5 months
Antipsychotic Related Outcome: Stanford Sleepiness Scale
Time frame: From enrollment to the end of study will be up to 5 months
Antipsychotic Related Outcome: Digit Symbol Substitution Test
Time frame: From enrollment to the end of study will be up to 5 months
Antipsychotic Related Outcome: Barnes Akathisia Scale
Time frame: From enrollment to the end of study will be up to 5 months
Antipsychotic Related Outcome: Simpson-Angus Scale
Time frame: From enrollment to the end of study will be up to 5 months
Antipsychotic Related Outcome: Abnormal Involuntary Movement Scale
Time frame: From enrollment to the end of study will be up to 5 months
Antipsychotic Related Outcome: UKU Side Effect Rating Scale
Time frame: From enrollment to the end of study will be up to 5 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Brain Insulin Sensitivity
Not yet recruiting
Long-term Effects of Avocado Consumption on Health in Pre-diabetic Individuals
Prediabetes, Brain Insulin Sensitivity
Recruiting
Long-Term Effects of Walnut Consumption on Brain Function
Healthy, Brain Insulin Sensitivity
RecruitingPhase 2/3
Exercise and Intranasal Insulin in Type 2 Diabetes
Type 2 Diabetes, Insulin Sensitivity/Resistance
Not yet recruiting
The Importance of Insulin Action in the Brain for the Immune System During Physical Activity-Overweight
Insulin Sensitivity
Active, not recruiting
Relative Contribution of Brain Insulin Action for Postprandial Metabolism
Glucose Metabolism Disorders
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mahavir Agarwal, MBBS, MD, PhD principal investigator
Centre for Addiction and Mental Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Haloperidol, Insulin Lispro and Saline in people with Brain Insulin Sensitivity and Healthy Controls, run by Centre for Addiction and Mental Health at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mahavir Agarwal, MBBS, MD, PhD (416-535-8501 ext. 30546, mahavir.agarwal@camh.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
RsFC between the anterior cingulate cortex of the salience network and the lateral parietal cortex of the DMN (time frame: From enrollment to the end of study will be up to 5 months). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2026.