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

Schizophrenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03943537
• Other study ID #: 2019P000664
• Status: Recruiting
• Phase: Phase 2
• Start date: October 1, 2019
• Est. completion date: January 26, 2024

Study information

• Verified date: December 2023
• Source: Mclean Hospital
• Contact: Jacey Anderson
• Phone: 617-855-3988
• Email: janderson75[@]mclean.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: January 26, 2024
• Est. primary completion date: January 26, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Bipolar I Disorder
• Mental Disorders
• Mood Disorders
• Psychosis
• Psychotic Disorders
• Schizo Affective Disorder
• Schizophrenia

Intervention

Drug:
• Intranasal Insulin
40 units Novolin R administered intranasally using ViaNase device.

Locations

Country	Name	City	State
United States	McLean Hospital	Belmont	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Mclean Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in brain Gln, Glu and GSH	Changes in glutamine (Gln), glutamate (Glu), and glutathione (GSH) concentration as measured by in vivo proton magnetic resonance spectroscopy	6 hours, pre- and post- 40 IU intranasal insulin
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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.	6 hours, pre- and post- 40 IU intranasal insulin
Primary	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.	6 hours, pre- and post- 40 IU intranasal insulin
Secondary	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
Secondary	Changes in brain inorganic phosphate concentration.	Changes in inorganic phosphate (Pi) concentration as measured by in vivo 31P magnetic resonance spectroscopy	6 hours, pre- and post- 40 IU intranasal insulin
Secondary	Change in fasting blood glucose levels.	Safety outcome.	6 hours, pre- and post- 40 IU intranasal insulin
Secondary	Change in fasting blood insulin levels.	Safety outcome.	6 hours, pre- and post- 40 IU intranasal insulin