Intranasal Insulin for Healthy Adults

(INI-CSF-MA Trial)

Overseen By Meghan E O'Brien

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: HealthPartners Institute

Disqualifiers: Chronic sinusitis, CNS disorders, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if insulin, a common diabetes medication, can reach the brain when administered as a nasal spray. Researchers believe intranasal insulin might improve memory and mood in individuals with brain-related conditions, but they must first confirm its ability to effectively target the brain. Participants will receive a low dose, high dose, or placebo to compare insulin levels in the brain. The study seeks healthy adults with normal body weight who can safely undergo a spinal tap. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to contribute to groundbreaking research.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using insulin through the nose is generally safe. Studies have found that severe side effects are rare, with no reports of low blood sugar or serious health problems. Some individuals have experienced mild side effects, such as temporary nasal irritation.

High doses of nasal insulin, up to 160 units, have been safely used in other situations, like during surgery. However, excessive absorption into the blood could pose a risk of low blood sugar.

Overall, research reports that nasal insulin is well-tolerated, with no major safety concerns. This suggests it is safe at the doses being studied in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about intranasal insulin because it offers a novel delivery method that bypasses the digestive system, allowing insulin to directly reach the brain. This is different from traditional insulin treatments, which are typically injected and target blood glucose levels. The intranasal route could potentially enhance cognitive functions by directly impacting brain insulin signaling. By testing both low and high doses, researchers aim to determine the most effective and safe dosage for influencing brain activity without affecting blood sugar control.

What evidence suggests that intranasal insulin could be effective for targeting the brain?

This trial will compare low and high doses of intranasal insulin with a placebo control. Research has shown that administering insulin through the nose might improve memory and mood in individuals with brain conditions like mild cognitive impairment and dementia. Studies have examined its effects on thinking skills in both patients and healthy individuals, yielding promising results. Evidence indicates that insulin can reach the brain when delivered intranasally, potentially enhancing brain function. Various studies have found this method safe, with no major safety concerns reported. Overall, while further research is necessary, early findings suggest that intranasal insulin could benefit brain health and function. ^{6 7 8 9 10}

Who Is on the Research Team?

Leah R Hanson, PhD

Principal Investigator

HealthPartners Institute

Kimberly Byrnes, PhD

Principal Investigator

Uniformed Services University of the Health Sciences

Are You a Good Fit for This Trial?

This trial is for healthy middle-aged adults. Participants must be willing to receive a nasal spray and undergo a lumbar puncture (spinal tap) to collect cerebrospinal fluid samples.

Inclusion Criteria

MOCA score ≥26

Subject must be proficient in speaking English to comply with instructions and measures for the study

Subject can provide written informed consent

Exclusion Criteria

Subject is pregnant or breast feeding

Subject has participated in a clinical trial investigation within 3 months of this study

I require insulin for my diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single intranasal dose of insulin or saline, followed by lumbar puncture and sample collection

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Intranasal Insulin

Trial Overview The study tests if insulin can reach the brain when given as a nasal spray. It compares the effects of two different doses of insulin with saline in 18 participants, who will have their cerebrospinal fluid and blood tested at several time points after dosing.

How Is the Trial Designed?

Group I: Low dose intranasal insulin Experimental Treatment 1 Intervention

One dose of 40 international units of regular insulin administered intranasally.

Group II: High dose Intranasal Insulin Experimental Treatment 1 Intervention

One dose of 80 international units of regular insulin administered intranasally.

Group III: Placebo Control Placebo Group 1 Intervention

One dose of 0.9% saline administered intranasally.

Intranasal Insulin is already approved in United States, European Union for the following indications:

Approved in United States as Intranasal insulin for:

• Diabetes

Approved in European Union as Intranasal insulin for:

• Diabetes

Who Is Running the Clinical Trial?

HealthPartners Institute

Lead Sponsor

Trials

196

Recruited

3,721,000+

Uniformed Services University of the Health Sciences

Collaborator

Trials

130

Recruited

91,100+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Department of Defense Congressionally Directed Medical Research Program

Collaborator

Trials

3

Recruited

640+

Published Research Related to This Trial

In a study involving 112 children and adolescents with type 1 diabetes, the combination of ultrashort acting insulin aspart with detemir or glargine showed a significant decrease in HbA1c levels, indicating improved blood sugar control over 12 and 24 weeks.

The use of detemir and glargine significantly reduced the risk of hypoglycemia compared to traditional NPH-insulin, while maintaining a stable body mass index in the detemir group, suggesting a safer and more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Basal insulin analogue versus traditional NPH insulin in basal bolus therapy of children and adolescents with type 1 diabetes]. Prikhodina, OA., Surikova, SV., Girsh, YV.[2020]

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]

The study demonstrated that administering intranasal insulin in a single nostril significantly enhances absorption, achieving higher maximum concentrations (C(max)) compared to dual nostril administration, with maximum levels reaching 96 µU/ml for a 75 U dose.

The enhanced absorption was attributed to the increased amount of insulin administered rather than the absorption enhancer CPE-215, indicating that higher doses of insulin can improve its effectiveness when delivered intranasally.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced absorption of Nasulin™, an ultrarapid-acting intranasal insulin formulation, using single nostril administration in normal subjects. Stote, R., Miller, M., Marbury, T., et al.[2021]

In a study involving 17 subjects with non-insulin dependent diabetes mellitus (NIDDM), nasally administered insulin significantly reduced post-meal blood sugar levels, with the most effective regimen achieving a 70% reduction in glucose levels over 240 minutes.

The nasal insulin was well-tolerated, with no cases of symptomatic hypoglycemia reported and only minor nasal irritation observed in a few instances, indicating it is a safe alternative for managing postprandial glucose levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal insulin: the effects of three dose regimens on postprandial glycaemic profiles in type II diabetic subjects. Coates, PA., Ismail, IS., Luzio, SD., et al.[2019]

The intranasal insulin formulation (Nasulin) was well tolerated in a study of 13 healthy male volunteers, showing a significant rise in serum insulin and a decrease in plasma glucose after administration.

Nasulin demonstrated a peak insulin absorption time of 10-20 minutes, with a relative absorption of 12.0% from the dominant nostril and 15.4% from the nondominant nostril, indicating it can be effectively administered regardless of nasal cycle.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of intranasal insulin spray (Nasulin) administered to healthy male volunteers: infuence of the nasal cycle. Leary, AC., Dowling, M., Cussen, K., et al.[2021]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11573730/

High‐dose intranasal insulin in an adaptive dose‐escalation ... These trials primarily focused on safety and feasibility, revealing that intranasal insulin was well‐tolerated and showed no safety concerns in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10306194/

Outcomes and clinical implications of intranasal insulin on ... The objective of this systematic review and meta-analysis is to evaluate the effects of INI on cognition in diverse patient populations and healthy individuals.

3. withpower.com withpower.com/trial/intranasal-insulin-for-healthy-adults-335b6

Intranasal Insulin for Healthy Adults · Info for Participants Intranasal insulin has been shown to improve memory and mood in patients with neurological diseases such as mild cognitive impairment and dementia, but more ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2451865425000833

Intranasal insulin for the treatment of alcohol use disorder The premise of this study is based on previous work showing that central insulin improved executive function [45], memory [46,47] and lowered impulsivity ...

5. ahajournals.org ahajournals.org/doi/10.1161/circ.146.suppl_1.105

Abstract 105: High-dose Intranasal Insulin In A ... We hypothesized that high-dose intranasal insulin can be safely delivered to healthy human subjects.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29508509/

Safety of intranasal human insulin: A review No cases of symptomatic hypoglycaemia or severe adverse events (AEs) were reported. Transient local side effects in the nasal area were frequently experienced ...

7. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/10.1111/cts.70071?af=R

High‐dose intranasal insulin in an adaptive dose‐escalation ... There are substantial clinical safety data for intranasal insulin in human trials, but there are no data suggesting the maximum tolerated dose.

8. sciencedirect.com sciencedirect.com/science/article/pii/S2666273623004175

Safety of intranasal insulin administration in patients ... The maximum safe dose during surgery is 160 IU. Higher doses can cause hypoglycemia due to absorption of insulin into the blood.

9. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2767376

Intranasal Insulin for the Treatment of Mild Cognitive ... This randomized clinical trial examines the safety, efficacy, and feasibility of intranasal insulin for the treatment of persons with mild ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT04292535

Safety and Efficacy of Combining Intranasal Insulin & Acute ... The safety of the protocol will be assessed using a symptom questionnaire assessing common symptoms of altered blood glucose and common side effects of ...