NCT03943537

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

Completed Phase 2 Results posted Last updated 15 April 2025

What this trial tests

Phase 2 trial testing Intranasal Insulin in Psychosis in 87 participants. Completed in 23 February 2024.

Timeline

1 October 2019

Primary endpoint
23 February 2024

23 February 2024

Quick facts

Lead sponsor	Mclean Hospital
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	other
Enrollment	87
Start date	1 October 2019
Primary completion	23 February 2024
Estimated completion	23 February 2024
Sites	1 location across United States

Drugs / interventions tested

• Intranasal Insulin — full drug profile →

Conditions studied

• Psychosis — all drugs for Psychosis →
• Schizophrenia — all drugs for Schizophrenia →
• Schizo Affective Disorder — all drugs for Schizo Affective Disorder →
• Bipolar I Disorder — all drugs for Bipolar I Disorder →

Sponsor

Mclean Hospital

Who can join

Adults 18 to 40, any sex, with Psychosis or Schizophrenia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Changes in Brain Redox State Primary · 6 hours, pre- and post- 40 IU intranasal insulin

Changes in brain NAD+/NADH ratio as measured by in vivo 31P magnetic resonance spectroscopy

Group	Value	95% CI
Patients	-0.269	-0.769 – 0.231
Controls	-0.485	-1.077 – 0.107

Changes in Brain ATP Primary · 6 hours, pre- and post- 40 IU intranasal insulin

Changes in ATP concentration as measured by in vivo 31P magnetic resonance spectroscopy

Group	Value	95% CI
Patients	0.017	-0.121 – 0.154
Controls	0.119	-0.006 – 0.244

Changes in Brain PCr Primary · 6 hours, pre- and post- 40 IU intranasal insulin

Changes in Phosphocreatine (PCr) concentration as measured by in vivo 31P magnetic resonance spectroscopy

Group	Value	95% CI
Patients	0.013	-0.030 – 0.056
Controls	-0.033	-0.070 – 0.005

Changes in Brain CK Primary · 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

Group	Value	95% CI
Patients	0.009	-0.012 – 0.029
Controls	0.006	-0.012 – 0.025

Changes in STROOP Color-word Interference Score Primary · 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.

Group	Value	95% CI
Patients	1.11	-0.38 – 2.61
Controls	0.94	-0.14 – 2.01

Changes in BACS Digit Sequencing Score Primary · 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.

Group	Value	95% CI
Patients	0.05	-0.35 – 0.45
Controls	0.16	-0.20 – 0.51

Changes in BACS Symbol Coding Primary · 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.

Group	Value	95% CI
Patients	0.74	0.37 – 1.11
Controls	0.83	0.58 – 1.09

Changes in BACS Verbal Fluency Scores Primary · 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.

Group	Value	95% CI
Patients	0.22	-0.07 – 0.50
Controls	0.43	0.14 – 0.72

Changes in Brain pH. Secondary · 6 hours, pre- and post- 40 IU intranasal insulin

Changes in pH as measured by in vivo 31P magnetic resonance spectroscopy

Group	Value	95% CI
Patients	0	-0.007 – 0.007
Controls	-0.004	-0.012 – 0.003

Changes in Brain Inorganic Phosphate Concentration. Secondary · 6 hours, pre- and post- 40 IU intranasal insulin

Changes in inorganic phosphate (Pi) concentration as measured by in vivo 31P magnetic resonance spectroscopy

Group	Value	95% CI
Patients	-0.002	-0.022 – 0.017
Controls	-0.020	-0.044 – 0.005

Change in Fasting Blood Glucose Levels. Secondary · 6 hours, pre- and post- 40 IU intranasal insulin

Safety outcome.

Group	Value	95% CI
Patients	4.62	1.35 – 7.89
Controls	2.17	0.56 – 3.77

Change in Fasting Blood Insulin Levels. Secondary · 6 hours, pre- and post- 40 IU intranasal insulin

Safety outcome.

Group	Value	95% CI
Patients	0.110	-0.634 – 0.854
Controls	-0.228	-0.877 – 0.421

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events data were collected on the day of the intervention visit with one-time intranasal insulin administration.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Patients

Serious: 0/21 (0%)

Deaths: 0/21

Controls

Serious: 0/18 (0%)

Deaths: 0/18

Other adverse events (2 terms — click to expand)

Reaction	System	Patients	Controls
Nasal irritation	Skin and subcutaneous tissue disorders	—	—
Headache with nausea after insulin administration	Nervous system disorders	—	—

Data from ClinicalTrials.gov NCT03943537 adverse events section.

Sponsor's own description

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.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Non-Invasive Strategies for Nose-to-Brain Drug Delivery.
   Trevino JT, Quispe RC, Khan F, Novak V. · · 2020 · cited 59× · PMID 33505777
2. Recent Advances in Intranasal Administration for Brain-Targeting Delivery: A Comprehensive Review of Lipid-Based Nanoparticles and Stimuli-Responsive Gel Formulations.
   Koo J, Lim C, Oh KT. · · 2024 · cited 57× · PMID 38414526 · DOI 10.2147/ijn.s439181
3. Intranasal Insulin Increases Brain Glutathione and Enhances Antioxidant Capacity in Healthy Participants but Not in Those With Early Psychotic Disorders.
   Chouinard VA, Feizi W, Chen X, Ren B, et al · · 2025 · cited 2× · PMID 39617344 · DOI 10.1016/j.bpsc.2024.11.018
4. High-dose intranasal insulin in an adaptive dose-escalation study in healthy human participants.
   Schmitzberger F, Fowler J, Hsu CH, Pai MP, et al · · 2024 · cited 1× · PMID 39558506 · DOI 10.1111/cts.70071