An interventional study of Olanzapine 2.5Mg Oral Tablet and Placebo in Insulin Resistance, Menstrual Cycle and Type 2 Diabetes, sponsored by Centre for Addiction and Mental Health. Active, not recruiting at 1 site in Canada. Open to female participants aged 18 Years to 35 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-28.
Sponsored by Centre for Addiction and Mental Health · Not applicable, Interventional, and Basic science
Females treated with antipsychotics have higher rates of comorbid metabolic syndrome than males. Despite this, females have historically been excluded from many mechanistic studies due to confounding effects of menstrual cycles. Recent evidence suggests that brain insulin resistance may be an underlying mechanism through which antipsychotics may exert their metabolic side effects. This study seeks to investigate how brain insulin action differs in females according to their menstrual cycle phase, and how a high metabolic liability agent such as olanzapine might interrupt these differential insulin effects. Young healthy females will be given olanzapine and intranasal insulin to test how these treatment combinations change brain processes. Participants will be tested during both the first half of their menstrual cycle (follicular phase) and the second half of their cycle (luteal phase). The investigators predict that intranasal insulin will change MRI-based measures in females, in a comparable way to males, in the follicular phase only. Adding olanzapine will block these effects of insulin in females in the follicular phase. This investigation has the potential to generate new knowledge in an area of significant unmet need. Demonstrating that antipsychotics disrupt brain insulin action, evidenced by inhibition of recognized effects of insulin on neuroimaging measures, will provide novel insights into currently poorly understood mechanisms.
BACKGROUND: Antipsychotics (APs) cause serious metabolic adverse effects, including weight gain and type 2 diabetes. Females are disproportionally more affected by this problem than males. While the pathophysiology of these effects remain unclear, brain insulin resistance (IR) is posited to be an important determinant. Currently there are no direct methods to investigate brain IR, but physiological response to intranasal insulin (INI) can be used as a surrogate marker. INI reliably suppresses endogenous glucose production, modulates brain activity, and improves cognition. In a proof-of-concept neuroimaging study at CAMH, the investigators investigated AP-induced brain IR using an INI challenge. As expected, preliminary data show acute olanzapine (OLA) administration attenuates INI-induced changes in cerebral blood flow and resting state activity; however, the findings are only observed in males. It was recently suggested that brain insulin action differs between sexes, and this may relate to menstrual phases. Specifically, IR is physiologically induced in the luteal, but not follicular phase of the menstrual cycle. Hence, this study seeks to explore if the effects of APs on brain insulin action in females is modulated by menstrual stages.
HYPOTHESES: 1) INI, but not intranasal placebo (INP) will modulate resting state activity in the brain in females during the follicular phase of their menstrual cycle but not the luteal phase; 2) oral OLA will inhibit all INI-induced effects, relative to oral PL, during the follicular phase. OLA will have no apparent effect on females in the luteal phase given pre-existing brain IR.
APPROACH AND METHODOLOGY: Fifteen healthy normal weight (BMI \<25 kg/m2), normal cycling female volunteers between the ages of 18-35 years will be recruited to participate in the study. In a single blind, crossover design, each participant will receive 4 treatment conditions (INP/PL, INI/PL, INP/OLA or INI-OLA) twice on 4 separate occasions (two visits per cycle phase). Each of the study periods will involve administration of OLA 5 mg HS (or PL) on day 0, OLA 10 mg HS (or PL) on day 1, and cognitive testing and MRI scanning on day 2. On Day 2, fasting blood work (glucose, insulin, c-peptide, olanzapine measures) will be followed by an MRI-based protocol of brain insulin action. This includes two MRI scans; one with intranasal insulin challenge (160 IU) and one with intranasal placebo. Study visits will take place 2-6 weeks apart to ensure specific menstrual phase across the four visits. Participants will undergo two visits during the follicular phase of the menstrual cycle (they will be scanned between day 4-10 of their menstrual cycle), and another two visits during the luteal phase of their menstrual cycle (between day 16-22, or within 5 days of next expected menses depending on individual cycle duration). Menstrual cycles will be tracked by self-report of the last three menstruation onset dates. Average cycle duration will be calculated to determine cycle phases. Based on this, participants will be invited to complete the visits during the specific windows of their follicular and luteal phase; measurement of sex hormones (progesterone, estrogen, luteinizing hormone (LH) and follicular stimulating hormone (FSH)) will be done at each visit to confirm cycle phase.
SIGNIFICANCE: Females suffer the most from AP-related metabolic adverse effects. Brain insulin action is increasingly being recognized as a potential mediator of these side effects. Disappointingly, females are an underrepresented population in the field because of the complex confounding effects of monthly hormonal variations. This is the first study to explore the effect of menstrual cycle phases on the anti-insulin action of APs. Thus, this investigation has the potential to generate new knowledge in an area of significant unmet need. Demonstrating that APs disrupt brain insulin action, evidenced by inhibition of recognized effects of INI on neuroimaging measures, will provide novel insights into currently poorly understood mechanisms.
2,969 studies on the registry are indexed under Insulin Resistance; 338 are open to participants now.
This study's planned enrollment of 15 is below the median of 40 across 2,369 interventional studies indexed under Insulin Resistance.
Browse Insulin Resistance studies →Centre for Addiction and Mental Health is the lead sponsor of 339 studies on the registry; 51 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will undergo two visits during the follicular phase of the menstrual cycle (they will be scanned between day 4-10 of their menstrual cycle). Each of the study periods will involve administration of OLA 5 mg HS (or PL) on day 0, OLA 10 mg HS (or PL) on day 1, and cognitive testing and MRI scanning on day 2. MRI assessments will occur 15 minutes after administering 160 International Units (IU) INI/INP.
Drug: Olanzapine 2.5Mg Oral Tablet · Drug: Placebo · Drug: Insulin Lispro 100 UNT/ML · Drug: Saline
Participants will undergo two visits during the luteal phase of the menstrual cycle (they will be scanned between day 16-22, or within 5 days of next expected menses depending on individual cycle duration). Each of the study periods will involve administration of OLA 5 mg HS (or PL) on day 0, OLA 10 mg HS (or PL) on day 1, and cognitive testing and MRI scanning on day 2. MRI assessments will occur 15 minutes after administering 160 International Units (IU) INI/INP.
Drug: Olanzapine 2.5Mg Oral Tablet · Drug: Placebo · Drug: Insulin Lispro 100 UNT/ML · Drug: Saline
Olanzapine capsules (2.5mg) will be administered during one research visit for each menstrual cycle phase. The dosing schedule is as follows: 1. Day 0- 5mg 2. Day 1- 10mg
Also known as: Apo-Olanzapine
Placebo capsules visually identical to those containing olanzapine will be administered according to the same dosing schedule during one research visit of each menstrual cycle phase.
Also known as: Olanzapine Placebo
Drug page: Insulin
At each visit, participants will be given an intranasal insulin challenge (160 IU) to assess brain insulin signalling via MRI based assay.
Also known as: Intranasal Insulin
At each visit, participants will be given an intranasal saline placebo (1.6 mL) in order to establish baseline brain insulin signalling via MRI based assay.
Also known as: Intranasal Saline
Resting State Functional Connectivity (assessed through Functional MRI)
Participants will complete 4 MRI scans to assess changes in resting state functional connectivity and activity across menstrual cycle phases and randomization conditions.Changes in resting state functional connectivity following intranasal insulin or placebo challenges, compared between the follicular and luteal phases of the menstrual cycle.
Time frame: Visits 1-4 (5-6 months); 2 visits during follicular phase, 2 visits during luteal phase. At each visit, either oral olanzapine or placebo is given. MRI #1 occurs after intranasal challenge #1 and MRI #2 occurs after intranasal challenge #2.
Visuospatial Memory
Participants will complete the Brief Visuospatial Memory Test (BVMT) to assess visuospatial memory outcomes across the randomization conditions. BVMT Scoring: 0-36 (minimum 0, maximum 36)
Time frame: Visits 1-4 (5-6 months) during break between MRI scan #1 and #2.
Processing Speed
Participants will complete the Digit-Symbol Substitution Test (DSST) to assess processing speed across the randomization conditions. DSST Scoring: 0-110 (minimum 0, maximum 110)
Time frame: Visits 1-4 (5-6 months) during break between MRI scan #1 and #2.
Plan to share: No
Started Jun 2024 (actual). Primary completion is estimated for Dec 2026, 30 months after the start.
Of 714 non-industry interventional studies with no phase under Insulin Resistance, half reached primary completion within 22 months of starting (the median), counting those still running; a quarter within 10 and three quarters within 41. This study's planned 30 months is above that.
Counting every sponsor, half of 754 studies reached it within 21 months; a quarter within 9 and three quarters within 40.
Since we started tracking on Sep 25, 2026, the dates moved once, on Sep 28, 2026: primary completion Aug 2026 → Dec 2026 and completion Aug 2026 → Dec 2026.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is active, not recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Olanzapine · Insulin · Saline Solution
Centre for Addiction and Mental Health →