Trial Outcomes & Findings for Effects of Intranasal Insulin on Neuroimaging Markers and Cognition in Patients With Psychotic Disorders (NCT NCT03943537)

NCT ID: NCT03943537

Last Updated: 2025-04-15

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 87 participants
• Primary outcome timeframe: 6 hours, pre- and post- 40 IU intranasal insulin
• Results posted on: 2025-04-15

Participant Flow

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.

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.

Participant milestones

Measure	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.	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.
Overall Study STARTED	41	46
Overall Study COMPLETED	21	18
Overall Study NOT COMPLETED	20	28

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Patients n=21 Participants 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.	Controls n=18 Participants 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.	Total n=39 Participants Total of all reporting groups
Age, Continuous	25.47 Years STANDARD_DEVIATION 5.29 • n=5 Participants	25.40 Years STANDARD_DEVIATION 3.64 • n=7 Participants	25.44 Years STANDARD_DEVIATION 4.55 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants	12 Participants n=7 Participants	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 hours, pre- and post- 40 IU intranasal insulin

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

Outcome measures

Measure	Patients n=18 Participants 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.	Controls n=16 Participants 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.
Changes in Brain Redox State	-0.269 ratio Interval -0.769 to 0.231	-0.485 ratio Interval -1.077 to 0.107

PRIMARY outcome

Timeframe: 6 hours, pre- and post- 40 IU intranasal insulin

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

Outcome measures

Measure	Patients n=20 Participants 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.	Controls n=17 Participants 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.
Changes in Brain ATP	0.017 mM Interval -0.121 to 0.154	0.119 mM Interval -0.006 to 0.244

PRIMARY outcome

Timeframe: 6 hours, pre- and post- 40 IU intranasal insulin

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

Outcome measures

Measure	Patients n=20 Participants 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.	Controls n=17 Participants 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.
Changes in Brain PCr	0.013 mM Interval -0.03 to 0.056	-0.033 mM Interval -0.07 to 0.005

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	Patients n=20 Participants 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.	Controls n=16 Participants 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.
Changes in Brain CK	0.009 s^-1 Interval -0.012 to 0.029	0.006 s^-1 Interval -0.012 to 0.025

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Patients n=21 Participants 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.	Controls n=18 Participants 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.
Changes in STROOP Color-word Interference Score	1.11 score on a scale Interval -0.38 to 2.61	0.94 score on a scale Interval -0.14 to 2.01

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Patients n=21 Participants 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.	Controls n=18 Participants 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.
Changes in BACS Digit Sequencing Score	0.05 score on a scale Interval -0.35 to 0.45	0.16 score on a scale Interval -0.2 to 0.51

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Patients n=21 Participants 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.	Controls n=18 Participants 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.
Changes in BACS Symbol Coding	0.74 units on a scale Interval 0.37 to 1.11	0.83 units on a scale Interval 0.58 to 1.09

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Patients n=21 Participants 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.	Controls n=18 Participants 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.
Changes in BACS Verbal Fluency Scores	0.22 z-score Interval -0.07 to 0.5	0.43 z-score Interval 0.14 to 0.72

SECONDARY outcome

Timeframe: 6 hours, pre- and post- 40 IU intranasal insulin

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

Outcome measures

Measure	Patients n=20 Participants 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.	Controls n=17 Participants 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.
Changes in Brain pH.	0 pH Interval -0.007 to 0.007	-0.004 pH Interval -0.012 to 0.003

SECONDARY outcome

Timeframe: 6 hours, pre- and post- 40 IU intranasal insulin

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

Outcome measures

Measure	Patients n=20 Participants 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.	Controls n=17 Participants 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.
Changes in Brain Inorganic Phosphate Concentration.	-0.002 mM Interval -0.022 to 0.017	-0.020 mM Interval -0.044 to 0.005

SECONDARY outcome

Timeframe: 6 hours, pre- and post- 40 IU intranasal insulin

Safety outcome.

Outcome measures

Measure	Patients n=21 Participants 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.	Controls n=18 Participants 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.
Change in Fasting Blood Glucose Levels.	4.62 mg/dL Interval 1.35 to 7.89	2.17 mg/dL Interval 0.56 to 3.77

SECONDARY outcome

Timeframe: 6 hours, pre- and post- 40 IU intranasal insulin

Safety outcome.

Outcome measures

Measure	Patients n=21 Participants 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.	Controls n=18 Participants 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.
Change in Fasting Blood Insulin Levels.	0.110 uIU/mL Interval -0.634 to 0.854	-0.228 uIU/mL Interval -0.877 to 0.421

SECONDARY outcome

Timeframe: 6 hours, pre- and post- 40 IU intranasal insulin

Changes in glutamate (Glu) concentration as measured by in vivo proton magnetic resonance spectroscopy

Outcome measures

Measure	Patients n=21 Participants 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.	Controls n=18 Participants 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.
Change in Brain Glutamate Concentration	-0.382 mM Interval -0.959 to 0.195	0.475 mM Interval -0.171 to 1.121

SECONDARY outcome

Timeframe: 6 hours, pre- and post- 40 IU intranasal insulin

Changes in glutamine (Gln) concentration as measured by in vivo proton magnetic resonance spectroscopy

Outcome measures

Measure	Patients n=21 Participants 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.	Controls n=18 Participants 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.
Changes in Brain Glutamine Concentration	-0.110 mM Interval -0.296 to 0.075	0.105 mM Interval -0.132 to 0.342

SECONDARY outcome

Timeframe: 6 hours, pre- and post- 40 IU intranasal insulin

Changes in glutathione (GSH) concentration as measured by in vivo proton magnetic resonance spectroscopy

Outcome measures

Measure	Patients n=21 Participants 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.	Controls n=18 Participants 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.
Changes in Brain Glutathione Concentration	-0.029 mM Interval -0.091 to 0.032	0.148 mM Interval 0.032 to 0.263

Adverse Events

Patients

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Controls

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Patients n=21 participants at risk 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.	Controls n=18 participants at risk 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.
Skin and subcutaneous tissue disorders Nasal irritation	0.00% 0/21 • Adverse events data were collected on the day of the intervention visit with one-time intranasal insulin administration.	5.6% 1/18 • Adverse events data were collected on the day of the intervention visit with one-time intranasal insulin administration.
Nervous system disorders Headache with nausea after insulin administration	0.00% 0/21 • Adverse events data were collected on the day of the intervention visit with one-time intranasal insulin administration.	5.6% 1/18 • Adverse events data were collected on the day of the intervention visit with one-time intranasal insulin administration.

Additional Information

Virginie-Anne Chouinard

McLean Hospital

Phone: 617-855-3034

Email: vchouinard@mclean.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place