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

Primary Purpose

Psychosis, Schizophrenia, Schizo Affective Disorder

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Intranasal Insulin
Sponsored by
Mclean Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Psychosis focused on measuring Psychosis, Insulin, Brain Metabolism, Cognition

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

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, protease inhibitors, or NRTI's.
  • 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) within the last 6 months
  • BMI > 35 or body weight > 350 lbs or BMI <18
  • DSM diagnosis of substance use disorder in the past 3 months
  • For Healthy Controls:
  • Taking medication other than birth control

Sites / Locations

  • McLean HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intranasal Insulin (40 IU)

Arm Description

40 IU Novolin-R insulin will be administered one time using the ViaNase intranasal delivery device.

Outcomes

Primary Outcome Measures

Changes in brain redox state
Changes in brain NAD+/NADH ratio as measured by in vivo 31P magnetic resonance spectroscopy
Changes in brain ATP
Changes in ATP concentration as measured by in vivo 31P magnetic resonance spectroscopy
Changes in brain PCr
Changes in Phosphocreatine (PCr) concentration as measured by in vivo 31P magnetic resonance spectroscopy
Changes in brain CK
Changes in creatine kinase (CK) enzyme rate as measured by in vivo 31P magnetic resonance spectroscopy
Changes in cognitive function
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.
Changes in domain-specific cognitive function.
Changes in BACS domain subscale scores (domain, range): working memory, 0-36; attention, 0-110; and verbal fluency, number of words generated over 60-sec trials. Higher scores indicate better cognitive function.

Secondary Outcome Measures

Changes in brain pH.
Changes in pH as measured by in vivo 31P magnetic resonance spectroscopy
Changes in brain inorganic phosphate concentration.
Changes in inorganic phosphate (Pi) concentration as measured by in vivo 31P magnetic resonance spectroscopy
Change in fasting blood glucose levels.
Safety outcome.
Change in fasting blood insulin levels.
Safety outcome.

Full Information

First Posted
May 7, 2019
Last Updated
October 17, 2023
Sponsor
Mclean Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03943537
Brief Title
Effects of Intranasal Insulin on Neuroimaging Markers and Cognition in Patients With Psychotic Disorders
Official Title
Effects of Intranasal Insulin on Neuroimaging Markers and Cognition in Patients With Psychotic Disorders
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2019 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
November 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mclean Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Psychosis, Schizophrenia, Schizo Affective Disorder, Bipolar I Disorder
Keywords
Psychosis, Insulin, Brain Metabolism, Cognition

7. Study Design

Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intranasal Insulin (40 IU)
Arm Type
Experimental
Arm Description
40 IU Novolin-R insulin will be administered one time using the ViaNase intranasal delivery device.
Intervention Type
Drug
Intervention Name(s)
Intranasal Insulin
Other Intervention Name(s)
Novolin R
Intervention Description
40 units Novolin R administered intranasally using ViaNase device.
Primary Outcome Measure Information:
Title
Changes in brain redox state
Description
Changes in brain NAD+/NADH ratio as measured by in vivo 31P magnetic resonance spectroscopy
Time Frame
6 hours, pre- and post- 40 IU intranasal insulin
Title
Changes in brain ATP
Description
Changes in ATP concentration as measured by in vivo 31P magnetic resonance spectroscopy
Time Frame
6 hours, pre- and post- 40 IU intranasal insulin
Title
Changes in brain PCr
Description
Changes in Phosphocreatine (PCr) concentration as measured by in vivo 31P magnetic resonance spectroscopy
Time Frame
6 hours, pre- and post- 40 IU intranasal insulin
Title
Changes in brain CK
Description
Changes in creatine kinase (CK) enzyme rate as measured by in vivo 31P magnetic resonance spectroscopy
Time Frame
6 hours, pre- and post- 40 IU intranasal insulin
Title
Changes in cognitive function
Description
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.
Time Frame
6 hours, pre- and post- 40 IU intranasal insulin
Title
Changes in domain-specific cognitive function.
Description
Changes in BACS domain subscale scores (domain, range): working memory, 0-36; attention, 0-110; and verbal fluency, number of words generated over 60-sec trials. Higher scores indicate better cognitive function.
Time Frame
6 hours, pre- and post- 40 IU intranasal insulin
Secondary Outcome Measure Information:
Title
Changes in brain pH.
Description
Changes in pH as measured by in vivo 31P magnetic resonance spectroscopy
Time Frame
6 hours, pre- and post- 40 IU intranasal insulin
Title
Changes in brain inorganic phosphate concentration.
Description
Changes in inorganic phosphate (Pi) concentration as measured by in vivo 31P magnetic resonance spectroscopy
Time Frame
6 hours, pre- and post- 40 IU intranasal insulin
Title
Change in fasting blood glucose levels.
Description
Safety outcome.
Time Frame
6 hours, pre- and post- 40 IU intranasal insulin
Title
Change in fasting blood insulin levels.
Description
Safety outcome.
Time Frame
6 hours, pre- and post- 40 IU intranasal insulin
Other Pre-specified Outcome Measures:
Title
Changes in brain Gln, Glu and GSH
Description
Changes in glutamine (Gln), glutamate (Glu), and glutathione (GSH) concentration as measured by in vivo proton magnetic resonance spectroscopy
Time Frame
6 hours, pre- and post- 40 IU intranasal insulin

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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, protease inhibitors, or NRTI's. 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jacey Anderson
Phone
617-855-3988
Email
janderson75@mclean.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Virginie-Anne Chouinard, M.D.
Phone
617-855-3034
Email
vchouinard@mclean.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Virginie-Anne Chouinard, M.D.
Organizational Affiliation
Mclean Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
McLean Hospital
City
Belmont
State/Province
Massachusetts
ZIP/Postal Code
02478
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Virginie-Anne Chouinard, MD
First Name & Middle Initial & Last Name & Degree
Dost Ongur, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

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

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