Intranasal Insulin for Insulin Resistance

Overseen By Jacqueline K Limberg, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Missouri-Columbia

Must not be taking: Metabolic, cardiovascular drugs

Disqualifiers: Diabetes, Hypertension, Cancer, others

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

Approved in 3 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 explores how insulin delivered through the nose affects insulin resistance by examining its impact on the brain and blood flow. Researchers aim to understand how this method could influence the body's nervous system and circulation. Participants will receive human insulin, known as intranasal insulin therapy, through a special nasal device. The trial seeks healthy adults aged 18-45 who do not smoke, use nicotine products, or take certain medications. As an Early Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants a chance to contribute to groundbreaking medical knowledge.

Will I have to stop taking my current medications?

The trial requires that you do not take any medications that affect metabolic, respiratory, cardiovascular, or autonomic functions. If your current medications fall into these categories, you may need to stop taking them to participate.

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

Research has shown that using human insulin as a nasal spray is generally safe. Studies have found that the dose used in this trial, 160 IU, is safe. At this amount, no major safety problems have been reported, although higher doses can cause low blood sugar if too much insulin enters the bloodstream. In other studies, participants using the nasal spray did not experience more side effects than those using a placebo, indicating it is well-tolerated. Overall, while more research is needed, current evidence supports the safety of nasal insulin at the tested dose. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for insulin resistance, which usually involve oral medications or lifestyle changes, this new approach delivers human insulin directly through the nose. This intranasal delivery method is unique because it allows insulin to bypass the digestive system and directly enter the brain, potentially improving insulin sensitivity more effectively. Researchers are excited about this because it could offer a faster and more targeted way to tackle insulin resistance, possibly enhancing brain health and overall metabolic control.

What evidence suggests that this trial's treatments could be effective for insulin resistance?

Research shows that using insulin through a nasal spray can enhance brain function. For example, studies have found it can boost memory and decision-making in people with diabetes. In this trial, participants in the insulin arms will receive human insulin administered intranasally. A specific dose of this treatment has changed brain activity, matching the amount used in the current trial. Importantly, this method of insulin delivery is safe and does not cause low blood sugar at the tested doses. These findings suggest that nasal insulin might help with insulin resistance by affecting brain function and blood flow. ^{2 6 7 8 9}

Who Is on the Research Team?

Jacqueline K Limberg, Ph.D.

Principal Investigator

University of Missouri-Columbia

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 18-45, with a BMI of 18-30 kg/m2 who don't smoke or use nicotine and are not pregnant or breastfeeding. It's not suitable for those with respiratory, metabolic, cardiovascular, autonomic diseases, autoimmune disorders, bleeding/clotting issues, stroke/neurovascular disease history, substance abuse problems including alcoholism and smoking history.

Inclusion Criteria

Non-pregnant/non-breastfeeding

Your body mass index (BMI) is between 18 and 30.

You have a body mass index (BMI) higher than 18 kg/m2.

Exclusion Criteria

I have a history of diabetes.

I am not on medications that affect my metabolism, breathing, heart, or involuntary functions.

I have a history of bleeding or clotting disorders.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive human insulin (160 IU) administered as a bolus using an intra-nasal device

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in muscle sympathetic nerve activity and cerebral blood flow

15 minutes

What Are the Treatments Tested in This Trial?

Interventions

• Carbon dioxide breathing
• Human insulin
• Neurovascular Coupling

Trial Overview The study investigates the effects of increased brain insulin on sympathetic nervous system activity and blood flow in the body and brain. Participants will undergo carbon dioxide breathing tests to assess neurovascular coupling after receiving human insulin intranasally.

How Is the Trial Designed?

Group I: Time Control (Doppler) Experimental Treatment 2 Interventions

Time control only

Group II: Insulin (MRI) Experimental Treatment 2 Interventions

Human insulin (160 IU) will be administered as a bolus using an intra-nasal device.

Group III: Insulin (Doppler) Experimental Treatment 3 Interventions

Human insulin (160 IU) will be administered as a bolus using an intra-nasal device.

Human insulin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Humulin R for:

• Type 1 diabetes
• Type 2 diabetes
• Gestational diabetes
• Diabetic ketoacidosis
• Hyperosmolar hyperglycemic states

Approved in United States as Humulin R for:

• Type 1 diabetes
• Type 2 diabetes
• Gestational diabetes
• Diabetic ketoacidosis
• Hyperosmolar hyperglycemic states

Approved in Canada as Humulin R for:

• Type 1 diabetes
• Type 2 diabetes
• Gestational diabetes
• Diabetic ketoacidosis
• Hyperosmolar hyperglycemic states

Who Is Running the Clinical Trial?

University of Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

Published Research Related to This Trial

Mixing human soluble insulin with newly developed crystalline zinc-suspension formulations significantly reduced the rise in free insulin levels and delayed the onset of action of the short-acting insulins in both normal and diabetic subjects.

This loss of solubility when mixing these insulins may limit their effectiveness in controlling blood sugar levels after meals, suggesting that careful consideration is needed when preparing insulin for injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of mixing human soluble and human crystalline zinc-suspension insulin: plasma insulin and blood glucose profiles after subcutaneous injection. Francis, AJ., Hanning, I., Alberti, KG.[2019]

In a study involving 56 participants with type 1 diabetes, the experimental regular insulin produced by Bioton S.A. showed bioequivalence to Humulin® R, indicating similar pharmacokinetic and pharmacodynamic effects.

The findings suggest that introducing affordable biosimilar regular insulins could significantly enhance access to insulin for socioeconomically disadvantaged patients, improving diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized pharmacokinetic and pharmacodynamic trial of two regular human insulins demonstrates bioequivalence in type 1 diabetes and availability of biosimilar insulin may improve access to this medication. Vencio, S., Caiado-Vencio, R., Caixeta, LF., et al.[2023]

In a study of 101 new patients with diabetes, human insulin treatment led to significant reductions in serum glucose and glycohemoglobin levels over 6 months, with no cases of insulin lipoatrophy or allergy reported, indicating its safety and efficacy.

In a transfer study involving 243 patients, switching from animal insulin to human insulin resulted in a slight increase in fasting serum glucose and ketonuria, but did not change insulin dosage or complication rates, suggesting that while human insulin may be slightly shorter acting, it remains a safe and effective alternative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The U.S. "new patient" and "transfer" studies. Galloway, JA., Peck, FB., Fineberg, SE., et al.[2019]

Intranasal insulin (INI) has been shown to improve global cognition in patients with Alzheimer's disease and mild cognitive impairment, based on a meta-analysis of 29 studies involving 1,726 participants.

However, INI did not demonstrate significant cognitive benefits in healthy individuals or other patient populations, indicating that its effects may be specific to certain cognitive disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes and clinical implications of intranasal insulin on cognition in humans: A systematic review and meta-analysis. Wu, S., Stogios, N., Hahn, M., et al.[2023]

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 37 individuals with type 2 diabetes, both Gansulin and Humulin N® effectively reduced HbA1c levels, indicating similar efficacy in glycemic control.

There were no significant differences in fasting plasma glucose, bedtime plasma glucose, or hypoglycemic events between the two insulin formulations, suggesting that Gansulin is as safe as Humulin N® for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study between two recombinant human NPH insulin formulations for the treatment of type 2 diabetes mellitus. Rassi, N., Moraes, SM., Alves, AG., et al.[2023]

In a study of 10 client-owned dogs with well-regulated diabetes mellitus, Humulin N effectively suppressed blood glucose levels by an average of 49.9%, indicating its efficacy as a treatment.

The duration of insulin action varied between 4 to 10 hours, and some dogs experienced an initial rise in blood glucose after insulin administration, highlighting the need for careful monitoring of postprandial glucose levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An investigation of the action of Neutral Protamine Hagedorn human analogue insulin in dogs with naturally occurring diabetes mellitus. Palm, CA., Boston, RC., Refsal, KR., et al.[2016]

In a clinical trial involving 211 diabetic patients over 12 weeks, both Yousilin R and Novolin R significantly reduced glycosylated hemoglobin A1c (HbA1c) levels, indicating effective blood sugar control, with no significant difference between the two treatments.

The safety profiles of Yousilin R and Novolin R were comparable, with similar rates of hypoglycemic events and other adverse effects, suggesting that Yousilin R is a safe alternative to Novolin R for diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy and safety of recombinant human insulin injection in the treatment of diabetic patients:a multicenter, randomized, controlled and open-labeled clinical trial]. Che, TT., Wang, X., Liu, YY., et al.[2014]

Human insulin (Actrapid) is absorbed more quickly and has a stronger hypoglycemic effect compared to porcine insulin (Actrapid) based on a study involving seven healthy men.

In a clinical trial with 12 type I diabetic patients, both human and porcine insulin achieved similar blood glucose control, indicating that the pharmacokinetic differences observed in healthy individuals do not significantly impact clinical outcomes in diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous use of regular human insulin (Novo): pharmacokinetics and continuous insulin infusion therapy. Sonnenberg, GE., Kemmer, FW., Cüppers, HJ., et al.[2011]

In a study involving 20 non-diabetic adults, intranasal insulin was found to be well tolerated with minimal risk of hypoglycemia, as only one hypoglycemic event occurred during placebo treatment and no significant changes in blood glucose levels were observed.

The treatment did not cause any nasal irritation or adverse effects on nasal functions, and it did not induce the production of diabetes-associated autoantibodies, suggesting a favorable safety profile for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasally administered insulin intended for prevention of type 1 diabetes--a safety study in healthy adults. Kupila, A., Sipilä, J., Keskinen, P., et al.[2011]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12205678/

Intranasal insulin for the treatment of alcohol use disorder IN insulin may be an ideal approach for treating multiple domains of AUD including memory, executive function and impulsivity.

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

Safety of intranasal insulin administration in patients ... This study provides important data on the maximum safe dose of intranasal insulin, which could help prevent hypoglycemia in patients undergoing cardiac surgery.

4. academic.oup.com academic.oup.com/jcem/article/103/1/253/4583441

Dose-Dependent Effects of Intranasal Insulin on Resting-State ... Nasal insulin dose-dependently modulated regional brain activity with the strongest effects after 160 U. However, this dose was accompanied by a transient ...

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/56/NCT02415556/Prot_SAP_001.pdf

1 Memory Advancement by Intranasal Insulin in Type 2 Diabetes ... Hypotheses and Aims: Memory Advancement by Intranasal Insulin in Type 2 Diabetes (MemAiD). Type 2 diabetes mellitus (DM) accelerates brain aging(1), ...

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

Safety of intranasal human insulin: A review Conclusions: Our retrospective review of published studies on intranasal insulin did not reveal any safety concerns; however, there were insufficient data to ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1111/dom.13279

Safety of intranasal human insulin: A review - Schmid - 2018 Tests on insulin that had been repacked into spray flasks showed that it had a chemical stability of up to 57 days. Conclusions. Our ...

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

Intranasal Insulin for the Treatment of Mild Cognitive ... Intranasal insulin was generally safe, with no differences in AE profiles between the insulin and placebo arms. This observation is consistent ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6483338/

Safety and preliminary efficacy of intranasal insulin for ... INI is safe in PD and MSA patients and may provide clinically relevant functional improvement. Larger studies are warranted to determine the INI effect.