Intranasal Insulin for Schizophrenia

Overseen By Laurie Hamel, MA

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must not be taking: Weight, lipid, antidiabetic, blood pressure

Disqualifiers: Diabetes, Liver disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates how nasal insulin delivery might impact thinking and memory issues in people with schizophrenia. Researchers believe insulin could aid both mental and physical health challenges associated with the condition. Participants will receive either intranasal insulin or a placebo and undergo a brain scan to assess their body's response. Individuals with schizophrenia and a body mass index (BMI) of 27 or less may qualify. Healthy individuals matched by age, sex, and BMI are also needed for comparison. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could enhance mental health treatments.

Do I have to stop taking my current medications for the trial?

The trial requires that you do not use weight, lipid, antidiabetic, or blood pressure medications, and you cannot take any medication that may interfere with the study or affect PET imaging results.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that administering insulin through the nose has been studied for its effects on schizophrenia and other mental health issues. In these studies, participants generally tolerated the treatment well. For example, one study on people with schizophrenia found that repeated nasal insulin administration did not cause significant side effects. Another study with a single dose also reported no major safety concerns.

Additionally, research has demonstrated that insulin can be safely delivered to the brain through the nose, with studies highlighting its potential positive effects. This suggests that this method is safe and can be used without causing harm. While more studies are needed to fully understand its long-term safety, current evidence supports the general safety of using insulin nasally for similar conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for schizophrenia, which often involve antipsychotic medications, intranasal insulin takes a completely different approach. This treatment is intriguing because it targets the brain directly through a nasal spray, potentially enhancing cognitive function without the side effects associated with traditional medications. Researchers are excited about its promise to improve symptoms swiftly and effectively, offering hope for a new way to manage schizophrenia.

What evidence suggests that intranasal insulin might be an effective treatment for schizophrenia?

This trial will compare the effects of intranasal insulin with a placebo in individuals with schizophrenia. Research has shown that using insulin through the nose as an additional treatment hasn't clearly improved thinking or memory in people with schizophrenia. Previous studies did not find significant improvements in mental health symptoms or metabolic processes with this treatment. Some trials also found no effect on memory or attention. Although it has potential, current evidence does not strongly support using intranasal insulin for cognitive issues in schizophrenia. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for right-handed individuals aged 17-45, who have been diagnosed with schizophrenia or related conditions and are either new to antipsychotic treatment or have had limited exposure. They should not be obese (BMI ≤27). The study also includes healthy subjects without these disorders.

Inclusion Criteria

You predominantly use your right hand for tasks.

I am between 17 and 45 years old.

I am between 17 and 45 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an intranasal insulin or placebo 15 minutes prior to the PET scan to measure [18F]-FDG brain uptake

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the PET scan

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Intranasal insulin
• Placebo

Trial Overview The study tests the effects of intranasal insulin on brain function in people with schizophrenia compared to healthy controls. It measures how the brain uses glucose after an insulin stimulus using a PET scan, aiming to understand cognitive and metabolic dysfunction in schizophrenia.

How Is the Trial Designed?

Group I: Schizophrenia Group Experimental Treatment 2 Interventions

Insulin (160IU) or placebo is administered intranasally 15 minutes prior to the PET scan.

Group II: Healthy Control Group Experimental Treatment 2 Interventions

Insulin (160 IU) or placebo is administered intranasally 15 minutes prior to the PET scan.

Intranasal insulin is already approved in United States, Canada, European Union, Japan, China, Switzerland for the following indications:

Approved in United States as Humulin for:

• Type 1 diabetes
• Type 2 diabetes

Approved in Canada as Novolin for:

• Type 1 diabetes
• Type 2 diabetes

Approved in European Union as Humalog for:

• Type 1 diabetes
• Type 2 diabetes

Approved in Japan as Novolog for:

• Type 1 diabetes
• Type 2 diabetes

Approved in China as Lantus for:

• Type 1 diabetes
• Type 2 diabetes

Approved in Switzerland as Levemir for:

• Type 1 diabetes
• Type 2 diabetes

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Published Research Related to This Trial

Intranasal insulin effectively reaches various brain regions, particularly the substantia nigra, where it binds to dopaminergic neurons and activates the Akt/PI3K survival signaling pathway, suggesting a potential neuroprotective mechanism against neurotoxicity.

Insulin levels peak in the brain at 15 minutes post-application and remain significantly elevated for up to 6 hours, indicating a sustained presence that could be beneficial for therapeutic interventions in neurodegenerative conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid transport of insulin to the brain following intranasal administration in rats. Fan, LW., Carter, K., Bhatt, A., et al.[2020]

In a study involving 35 participants with mild cognitive impairment or mild Alzheimer's disease, intranasal glulisine did not show significant improvements in cognitive function compared to a placebo over 3 and 6 months.

The treatment was generally safe and well-tolerated, with similar rates of adverse events between groups, although intranasal glulisine was associated with higher instances of nasal irritation and respiratory symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II, Single-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Therapeutic Efficacy of Intranasal Glulisine in Amnestic Mild Cognitive Impairment and Probable Mild Alzheimer's Disease. Rosenbloom, M., Barclay, TR., Kashyap, B., et al.[2022]

Intranasal insulin has shown promise as a rapid-acting treatment for smoking cessation by effectively reducing nicotine cravings through a unique 'nose-to-brain' delivery method that bypasses the blood-brain barrier, as supported by clinical trials.

The review also explores the potential of intranasal insulin to address other factors that contribute to smoking persistence, such as weight gain, impulsive behavior, and anhedonia, suggesting it may enhance overall smoking cessation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Mediators of Smoking Persistence with Intranasal Insulin. Hamidovic, A.[2020]

In a trial involving 60 adults with mild cognitive impairment (MCI) or Alzheimer's disease (AD), intranasal insulin detemir at a dose of 40 IU showed significant improvements in memory and working memory compared to placebo, particularly benefiting APOE-ε4 carriers.

The study found that higher baseline insulin resistance predicted greater cognitive improvement with the 40 IU dose, but no significant effects were observed on daily functioning or executive functioning, indicating a specific impact on cognitive aspects rather than overall daily activities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia. Claxton, A., Baker, LD., Hanson, A., et al.[2022]

In a study of 36 adults with mild cognitive impairment or Alzheimer's disease, regular insulin administered intranasally for four months significantly improved memory compared to placebo, while insulin detemir did not show similar benefits.

Regular insulin treatment also helped preserve brain volume and reduced certain Alzheimer's disease biomarkers, suggesting it may have a protective effect on brain health in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer's Disease Biomarkers: A Pilot Clinical Trial. Craft, S., Claxton, A., Baker, LD., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5366038/

No effect of adjunctive, repeated dose intranasal insulin ... The 8-week study did not show any beneficial effects of intranasal insulin treatment on psychopathology and cognition in patients with schizophrenia. ... data ...

2. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT00646581

Effect of Single Dose Intranasal Insulin On Cognitive ... The investigators propose a single dose, double-blinded, placebo-controlled trial of intranasal insulin in 40 subjects with schizophrenia or ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3622829/

No effect of adjunctive, repeated dose intranasal insulin ... In the present study, adjunctive therapy of intranasal insulin did not seem to improve body metabolism in patients with schizophrenia. The implications for ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0149763424003762

Central effects of acute intranasal insulin on neuroimaging ... No effect of single-dose intranasal insulin treatment on verbal memory and sustained attention in patients with schizophrenia. J. Clin. Psychopharmacol., 31 ...

5. mayo.edu mayo.edu/research/clinical-trials/cls-20148833

The Study of Nasal Insulin in the Fight Against ... ... psychosis, major depression, bipolar disorder, alcohol or substance abuse ... To examine the effects of intranasal insulin administration on cognition ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00646581?cond=%22Schizophrenia%22&intr=%22Insulin%22&viewType=Table&rank=2&tab=results

Effect of Single Dose Intranasal Insulin On Cognitive ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 ... Subjects who met DSM-IV criteria for schizophrenia or schizoaffective ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11153287/

Insulin Delivery to the Brain via the Nasal Route Recent trials have demonstrated the positive effects of nasal insulin in individuals with schizophrenia, bipolar disorder, depression ...