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

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to find out whether insulin, a drug approved by the FDA for the treatment of diabetes mellitus, reaches the brain and spinal cord when delivered as a nasal spray (intranasally). Intranasal insulin has been shown to improve memory and mood in patients with neurological diseases such as mild cognitive impairment and dementia, but more evidence is needed to support the ability to effectively target the brain through intranasal routes. 18 healthy middle-aged adults will be randomly assigned to receive a single intranasal dose of 40 units insulin ("low dose" group), 80 units insulin ("high dose" group), or saline (placebo, or control group). Participants will undergo an image-guided lumbar puncture (spinal tap) performed by a study clinician. Samples of cerebrospinal fluid (a fluid surrounding the brain and spinal cord) and blood will be collected at 5 timepoints during the lumbar puncture: once prior to the administration of intranasal insulin, and again at 10, 20, 30, and 40 minutes after the dose is given. Samples will be tested to determine the level of insulin detected in the cerebrospinal fluid and blood at each time point. Results of this study will provide essential information about the ability of insulin to reach the brain after intranasal administration.

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 intranasal insulin safe for healthy adults?

Intranasal insulin has been studied in healthy volunteers and other groups, showing good safety with no serious side effects reported. Some studies noted mild nasal irritation, but overall, it was well-tolerated. ^{1 2 3 4 5}

How is intranasal insulin different from other insulin treatments?

Intranasal insulin is unique because it is administered through the nose, allowing for rapid absorption directly into the bloodstream, which can be faster than traditional injections. This method also shows potential benefits for cognitive improvement in conditions like mild cognitive impairment or early-stage Alzheimer's disease. ^{1 2 4 6 7}

What data supports the effectiveness of the drug intranasal insulin for healthy adults?

Research shows that intranasal insulin, like Nasulin, can be absorbed effectively through the nasal passage, which suggests it could be a viable way to deliver insulin quickly. Additionally, insulin detemir, a component of the treatment, has been shown to effectively manage blood sugar levels in people with diabetes, indicating its potential effectiveness in other uses. ^{1 4 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+

Published Research Related to This Trial

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]

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 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 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]

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]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of intranasal insulin spray (Nasulin) administered to healthy male volunteers: infuence of the nasal cycle. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Enhanced absorption of Nasulin™, an ultrarapid-acting intranasal insulin formulation, using single nostril administration in normal subjects. [2021]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Basal insulin analogue versus traditional NPH insulin in basal bolus therapy of children and adolescents with type 1 diabetes]. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Insulin detemir is characterized by a consistent pharmacokinetic profile across age-groups in children, adolescents, and adults with type 1 diabetes. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Insulin analogues (insulin detemir and insulin aspart) versus traditional human insulins (NPH insulin and regular human insulin) in basal-bolus therapy for patients with type 1 diabetes. [2022]

6. 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]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

Intranasal insulin: the effects of three dose regimens on postprandial glycaemic profiles in type II diabetic subjects. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Nasal absorption of mixtures of fast-acting and long-acting insulins. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Intranasal insulin: from nose to brain. [2011]