Effects of Intranasal Insulin on Neuroimaging Markers and Cognition in Patients With Psychotic Disorders

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03943537

Enrollment

Registered

2019-05-09

Start date

2019-10-01

Completion date

2024-02-23

Last updated

2026-09-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Bipolar I Disorder, Psychosis, Schizo Affective Disorder, Schizophrenia

Keywords

Psychosis, Insulin, Brain Metabolism, Cognition

Brief summary

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.

Detailed description

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.

Interventions

DRUGIntranasal Insulin

40 units Novolin R administered intranasally using ViaNase device.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 40 Years

Healthy volunteers

Yes

Inclusion criteria

* Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses of schizophrenia, schizoaffective disorder or bipolar disorder with psychotic features OR * Healthy Controls (no history of DSM psychiatric diagnoses, nor history of the same in first-degree relatives)

Exclusion criteria

* Psychiatric hospitalization within the last 4 weeks * Unstable/active disease or potential contraindications, such as liver disease, kidney disease, uncontrolled hypertension, significant or unstable medical illness * Currently prescribed: antidiabetic agents, including oral antidiabetic medications and insulin, intranasal medication, steroids, weight loss agents * Pregnant or breast-feeding, not using an effective form of contraception for at least 3 months, and/or not abstinent for 1 month prior to enrollment * History of significant head injury * Contraindication to MRI scans (claustrophobia, cardiac pacemakers, metal clips and stents on blood vessels, artificial heart valves, artificial arms, hands, legs, etc., brain stimulator devices, implanted drug pumps, ear implants, eye implants or known metal fragments in eyes, exposure to shrapnel or metal filings, other metallic surgical hardware in vital areas, certain tattoos with metallic ink, certain transdermal patches, metal-containing IUDs). * Medical conditions preventing blood draws * History of electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) within the last 3 months * BMI \> 35 or body weight \> 350 lbs or BMI \<18 * DSM diagnosis of substance use disorder in the past month * For Healthy Controls: * Taking medication other than birth control

Design outcomes

Primary

Measure	Time frame	Description
Changes in BACS Digit Sequencing Score	6 hours, pre- and post- 40 IU intranasal insulin	Changes in BACS digit sequencing scores, ranging from 0 - 36. Higher scores indicate better cognitive function.
Changes in BACS Symbol Coding	6 hours, pre- and post- 40 IU intranasal insulin	Changes in BACS Symbol Coding test, with scores ranging from 0 - 110. Higher scores indicate better cognitive function.
Changes in BACS Verbal Fluency Scores	6 hours, pre- and post- 40 IU intranasal insulin	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.
Changes in Brain Redox State	6 hours, pre- and post- 40 IU intranasal insulin	Changes in brain NAD+/NADH ratio as measured by in vivo 31P magnetic resonance spectroscopy
Changes in Brain ATP	6 hours, pre- and post- 40 IU intranasal insulin	Changes in ATP concentration as measured by in vivo 31P magnetic resonance spectroscopy
Changes in Brain PCr	6 hours, pre- and post- 40 IU intranasal insulin	Changes in Phosphocreatine (PCr) concentration as measured by in vivo 31P magnetic resonance spectroscopy
Changes in Brain CK	6 hours, pre- and post- 40 IU intranasal insulin	Changes in creatine kinase (CK) enzyme rate as measured by in vivo 31P magnetic resonance spectroscopy
Changes in STROOP Color-word Interference Score	6 hours, pre- and post- 40 IU intranasal insulin	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.

Secondary

Measure	Time frame	Description
Change in Fasting Blood Insulin Levels.	6 hours, pre- and post- 40 IU intranasal insulin	Safety outcome.
Changes in Brain Glutathione Concentration	6 hours, pre- and post- 40 IU intranasal insulin	Changes in glutathione (GSH) concentration as measured by in vivo proton magnetic resonance spectroscopy
Change in Brain Glutamate Concentration	6 hours, pre- and post- 40 IU intranasal insulin	Changes in glutamate (Glu) concentration as measured by in vivo proton magnetic resonance spectroscopy
Changes in Brain pH.	6 hours, pre- and post- 40 IU intranasal insulin	Changes in pH as measured by in vivo 31P magnetic resonance spectroscopy
Changes in Brain Inorganic Phosphate Concentration.	6 hours, pre- and post- 40 IU intranasal insulin	Changes in inorganic phosphate (Pi) concentration as measured by in vivo 31P magnetic resonance spectroscopy
Change in Fasting Blood Glucose Levels.	6 hours, pre- and post- 40 IU intranasal insulin	Safety outcome.
Changes in Brain Glutamine Concentration	6 hours, pre- and post- 40 IU intranasal insulin	Changes in glutamine (Gln) concentration as measured by in vivo proton magnetic resonance spectroscopy

Countries

United States

Contacts

PRINCIPAL_INVESTIGATORVirginie-Anne Chouinard, M.D.

Mclean Hospital

Participant flow

Recruitment details

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.

Pre-assignment details

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 by arm

Arm	Count
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.	21
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.	18
Total	39

Baseline characteristics

Characteristic	Controls	Total	Patients
Age, Continuous	25.40 Years STANDARD_DEVIATION 3.64	25.44 Years STANDARD_DEVIATION 4.55	25.47 Years STANDARD_DEVIATION 5.29
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants	9 Participants	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants	30 Participants	18 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	2 Participants	8 Participants	6 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	2 Participants	4 Participants	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	14 Participants	27 Participants	13 Participants
Sex: Female, Male Female	10 Participants	20 Participants	10 Participants
Sex: Female, Male Male	8 Participants	19 Participants	11 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 21	0 / 18
other Total, other adverse events	0 / 21	2 / 18
serious Total, serious adverse events	0 / 21	0 / 18

Outcome results

Primary

Changes in BACS Digit Sequencing Score

Changes in BACS digit sequencing scores, ranging from 0 - 36. Higher scores indicate better cognitive function.