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This clinical trial is a single center, single dose study of the acute effects of intranasal insulin on energy metabolism and cognitive function in patients with schizophrenia, schizoaffective and bipolar disorders, compared and healthy controls.
Psychotic disorders are common and severe psychiatric disorders. Despite advances in understanding the pathophysiology of these disorders, more effective and tolerable treatments are still needed. Evidence suggests that energy metabolism is altered in psychotic disorders. The investigators recently developed non-invasive MRI-based techniques to quantify redox balance and ATP generation in the brain. Targeting insulin pathways in the brain may allow for modulating abnormalities in energy metabolism. The investigators seek to examine whether intranasal insulin can modulate energy metabolism and improve cognition in patients with psychotic disorders. The study will use magnetic resonance spectroscopy (MRS) technology to measure in vivo energy metabolism processes in the brain, before and after the administration of intranasal insulin. Investigators will also measure changes in cognition with the administration of intranasal insulin.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intranasal Insulin (40 IU) | Experimental | 40 IU Novolin-R insulin will be administered one time using the ViaNase intranasal delivery device. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intranasal Insulin | Drug | 40 units Novolin R administered intranasally using ViaNase device. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Brain Redox State | Changes in brain NAD+/NADH ratio as measured by in vivo 31P magnetic resonance spectroscopy | 6 hours, pre- and post- 40 IU intranasal insulin |
| Changes in Brain ATP | Changes in ATP concentration as measured by in vivo 31P magnetic resonance spectroscopy | 6 hours, pre- and post- 40 IU intranasal insulin |
| Changes in Brain PCr | Changes in Phosphocreatine (PCr) concentration as measured by in vivo 31P magnetic resonance spectroscopy | 6 hours, pre- and post- 40 IU intranasal insulin |
| Changes in Brain CK | Changes in creatine kinase (CK) enzyme rate as measured by in vivo 31P magnetic resonance spectroscopy | 6 hours, pre- and post- 40 IU intranasal insulin |
| Changes in STROOP Color-word Interference Score | Changes in STROOP assessment color-word condition interference score. This score is calculated as follows, with C being the number of items answered correctly in the color condition, W being the number answered correctly in the word condition, and CW being the number of items answered correctly in the color-word condition: CW - (C x W)/(C+W). Higher scores indicate better cognitive function. | 6 hours, pre- and post- 40 IU intranasal insulin |
| Changes in BACS Digit Sequencing Score | Changes in BACS digit sequencing scores, ranging from 0 - 36. Higher scores indicate better cognitive function. | 6 hours, pre- and post- 40 IU intranasal insulin |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Brain pH. | Changes in pH as measured by in vivo 31P magnetic resonance spectroscopy | 6 hours, pre- and post- 40 IU intranasal insulin |
| Changes in Brain Inorganic Phosphate Concentration. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Virginie-Anne Chouinard, M.D. | Mclean Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| McLean Hospital | Belmont | Massachusetts | 02478 | United States |
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After phone screening, participants were asked to complete an in-person screening visit to confirm study eligibility. The visit included a structured clinical interview (SCID-5) to confirm psychiatric diagnosis, psychiatric scales, blood draw, and medical history interview. Based on the results of these assessments, participants were excluded if they had unstable or active medical problems, diabetes, active substance use disorder, pregnancy, or MRI contraindications.
Participants with schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features were recruited from a variety of McLean Hospital outpatient settings, the Registry of Research Participants for the Psychotic Disorders Division, and online advertising methods. A phone screening was conducted before enrollment to assess basic eligibility criteria. Healthy controls were recruited through online advertisements.
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| ID | Title | Description |
|---|---|---|
| FG000 | Patients | Patients with diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses of schizophrenia, schizoaffective disorder or bipolar disorder with psychotic features. All participants received 40 IU Novolin-R insulin administered one time using the ViaNase intranasal delivery device. |
| FG001 | Controls | Healthy Controls (no history of DSM psychiatric diagnoses, nor history of the same in first-degree relatives). All participants received 40 IU Novolin-R insulin administered one time using the ViaNase intranasal delivery device. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Patients | 21 patients with diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses of schizophrenia, schizoaffective disorder or bipolar disorder with psychotic features. All participants received 40 IU Novolin-R insulin administered one time using the ViaNase intranasal delivery device. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Changes in Brain Redox State | Changes in brain NAD+/NADH ratio as measured by in vivo 31P magnetic resonance spectroscopy | Posted | Mean | 95% Confidence Interval | ratio | 6 hours, pre- and post- 40 IU intranasal insulin |
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Adverse events data were collected on the day of the intervention visit with one-time intranasal insulin administration.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Patients | 21 patients with diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses of schizophrenia, schizoaffective disorder or bipolar disorder with psychotic features. All participants received 40 IU Novolin-R insulin administered one time using the ViaNase intranasal delivery device. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasal irritation | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Virginie-Anne Chouinard | McLean Hospital | 617-855-3034 | vchouinard@mclean.harvard.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 24, 2019 | Feb 18, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D011618 | Psychotic Disorders |
| D012559 | Schizophrenia |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
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| ID | Term |
|---|---|
| D007328 | Insulin |
| ID | Term |
|---|---|
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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| Changes in BACS Symbol Coding | Changes in BACS Symbol Coding test, with scores ranging from 0 - 110. Higher scores indicate better cognitive function. | 6 hours, pre- and post- 40 IU intranasal insulin |
| Changes in BACS Verbal Fluency Scores | Changes in BACS verbal fluency subscale z-scores, measured by number of words generated over 60-second trials. A z-score of 0 indicates the population mean. Higher scores indicate better cognitive function. | 6 hours, pre- and post- 40 IU intranasal insulin |
Changes in inorganic phosphate (Pi) concentration as measured by in vivo 31P magnetic resonance spectroscopy
| 6 hours, pre- and post- 40 IU intranasal insulin |
| Change in Fasting Blood Glucose Levels. | Safety outcome. | 6 hours, pre- and post- 40 IU intranasal insulin |
| Change in Fasting Blood Insulin Levels. | Safety outcome. | 6 hours, pre- and post- 40 IU intranasal insulin |
| Change in Brain Glutamate Concentration | Changes in glutamate (Glu) concentration as measured by in vivo proton magnetic resonance spectroscopy | 6 hours, pre- and post- 40 IU intranasal insulin |
| Changes in Brain Glutamine Concentration | Changes in glutamine (Gln) concentration as measured by in vivo proton magnetic resonance spectroscopy | 6 hours, pre- and post- 40 IU intranasal insulin |
| Changes in Brain Glutathione Concentration | Changes in glutathione (GSH) concentration as measured by in vivo proton magnetic resonance spectroscopy | 6 hours, pre- and post- 40 IU intranasal insulin |
| Controls |
18 healthy Controls (no history of DSM psychiatric diagnoses, nor history of the same in first-degree relatives). All participants received 40 IU Novolin-R insulin administered one time using the ViaNase intranasal delivery device. |
| BG002 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
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| Primary | Changes in Brain ATP | Changes in ATP concentration as measured by in vivo 31P magnetic resonance spectroscopy | Posted | Mean | 95% Confidence Interval | mM | 6 hours, pre- and post- 40 IU intranasal insulin |
|
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| Primary | Changes in Brain PCr | Changes in Phosphocreatine (PCr) concentration as measured by in vivo 31P magnetic resonance spectroscopy | Posted | Mean | 95% Confidence Interval | mM | 6 hours, pre- and post- 40 IU intranasal insulin |
|
|
|
| Primary | Changes in Brain CK | Changes in creatine kinase (CK) enzyme rate as measured by in vivo 31P magnetic resonance spectroscopy | Posted | Mean | 95% Confidence Interval | s^-1 | 6 hours, pre- and post- 40 IU intranasal insulin |
|
|
|
| Primary | Changes in STROOP Color-word Interference Score | Changes in STROOP assessment color-word condition interference score. This score is calculated as follows, with C being the number of items answered correctly in the color condition, W being the number answered correctly in the word condition, and CW being the number of items answered correctly in the color-word condition: CW - (C x W)/(C+W). Higher scores indicate better cognitive function. | Posted | Mean | 95% Confidence Interval | score on a scale | 6 hours, pre- and post- 40 IU intranasal insulin |
|
|
|
| Primary | Changes in BACS Digit Sequencing Score | Changes in BACS digit sequencing scores, ranging from 0 - 36. Higher scores indicate better cognitive function. | Posted | Mean | 95% Confidence Interval | score on a scale | 6 hours, pre- and post- 40 IU intranasal insulin |
|
|
|
| Primary | Changes in BACS Symbol Coding | Changes in BACS Symbol Coding test, with scores ranging from 0 - 110. Higher scores indicate better cognitive function. | Posted | Mean | 95% Confidence Interval | units on a scale | 6 hours, pre- and post- 40 IU intranasal insulin |
|
|
|
| Primary | Changes in BACS Verbal Fluency Scores | Changes in BACS verbal fluency subscale z-scores, measured by number of words generated over 60-second trials. A z-score of 0 indicates the population mean. Higher scores indicate better cognitive function. | Posted | Mean | 95% Confidence Interval | z-score | 6 hours, pre- and post- 40 IU intranasal insulin |
|
|
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| Secondary | Changes in Brain pH. | Changes in pH as measured by in vivo 31P magnetic resonance spectroscopy | Posted | Mean | 95% Confidence Interval | pH | 6 hours, pre- and post- 40 IU intranasal insulin |
|
|
|
| Secondary | Changes in Brain Inorganic Phosphate Concentration. | Changes in inorganic phosphate (Pi) concentration as measured by in vivo 31P magnetic resonance spectroscopy | Posted | Mean | 95% Confidence Interval | mM | 6 hours, pre- and post- 40 IU intranasal insulin |
|
|
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| Secondary | Change in Fasting Blood Glucose Levels. | Safety outcome. | Posted | Mean | 95% Confidence Interval | mg/dL | 6 hours, pre- and post- 40 IU intranasal insulin |
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| Secondary | Change in Fasting Blood Insulin Levels. | Safety outcome. | Posted | Mean | 95% Confidence Interval | uIU/mL | 6 hours, pre- and post- 40 IU intranasal insulin |
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| Secondary | Change in Brain Glutamate Concentration | Changes in glutamate (Glu) concentration as measured by in vivo proton magnetic resonance spectroscopy | Posted | Mean | 95% Confidence Interval | mM | 6 hours, pre- and post- 40 IU intranasal insulin |
|
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| Secondary | Changes in Brain Glutamine Concentration | Changes in glutamine (Gln) concentration as measured by in vivo proton magnetic resonance spectroscopy | Posted | Mean | 95% Confidence Interval | mM | 6 hours, pre- and post- 40 IU intranasal insulin |
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| Secondary | Changes in Brain Glutathione Concentration | Changes in glutathione (GSH) concentration as measured by in vivo proton magnetic resonance spectroscopy | Posted | Mean | 95% Confidence Interval | mM | 6 hours, pre- and post- 40 IU intranasal insulin |
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| 0 |
| 21 |
| 0 |
| 21 |
| 0 |
| 21 |
| EG001 | Controls | 18 healthy Controls (no history of DSM psychiatric diagnoses, nor history of the same in first-degree relatives). All participants received 40 IU Novolin-R insulin administered one time using the ViaNase intranasal delivery device. | 0 | 18 | 0 | 18 | 2 | 18 |
| Headache with nausea after insulin administration | Nervous system disorders | Non-systematic Assessment |
|
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| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |