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

Trial Summary

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.

How is intranasal insulin different from other drugs for schizophrenia?

Intranasal insulin is unique because it is delivered through the nose, allowing it to reach the brain directly and potentially improve brain function, unlike traditional schizophrenia treatments that often target neurotransmitter imbalances. This method bypasses the blood-brain barrier, which is a challenge for many drugs, and has shown promise in improving cognitive functions in other conditions like Alzheimer's disease. ^{1 2 3 4 5}

What is the purpose of this trial?

Cognitive impairment (such as challenges in thinking and memory) is a core aspect of schizophrenia (SCZ), contributing to disability and poor functional outcomes. Additionally, almost half of the patients with SCZ are obese, the prevalence of type 2 diabetes is 3-6 times higher, and life expectancy is lower by 15-20 years compared to the general population. This is relevant as metabolic syndrome and diabetes are both associated with worse cognition among SCZ patients. Recent work studying the relationships between metabolic health and cognition has encouraged a new way of thinking about SCZ as both a metabolic and cognitive disorder. Brain insulin is involved in several processes relevant to SCZ, and abnormal brain insulin action may help explain both cognitive and metabolic abnormalities in patients with SCZ, but this has not been examined previously. Glucose uptake in several brain regions relevant to SCZ has been shown to be partially dependent on insulin. Therefore, in this study, the researchers will measure glucose uptake in the brain using an 18F-fluorodeoxyglucose (\[18F\]-FDG) positron emission tomography (PET) scan after an intranasal insulin stimulus, and will compare this measure between patients with SCZ and healthy controls.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. New Zealand 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. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

3. Netherlands 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. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer's Disease Biomarkers: A Pilot Clinical Trial. [2022]

5. India pubmed.ncbi.nlm.nih.gov

Rapid transport of insulin to the brain following intranasal administration in rats. [2020]