Nasal Insulin for Cognitive Impairment

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Must not be taking: Insulin, Anticoagulants, Anticonvulsants, others

Disqualifiers: Dementia, Stroke, Epilepsy, Diabetes, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 2

Duration: 2 visits

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a device that delivers insulin through the nose (intranasal insulin) to evaluate its effects on memory and brain function. Insulin, a hormone that typically lowers blood sugar, might also benefit cognitive health. Participants will either start with insulin and switch to a placebo or vice versa to compare results. The trial seeks individuals who are fluent in English, have mild memory issues (but not dementia), and haven't recently used insulin. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial requires that your medications be stable for at least 4 weeks before the screening and study visits. Some medications, like insulin, anti-diabetic drugs, anticoagulants, and certain others, are not allowed during the trial.

What prior data suggests that this device is safe for administering insulin intra-nasally?

Research has shown that using insulin through the nose is safe and generally well-tolerated. For instance, a study with Alzheimer's patients found no major safety concerns. Another study involving people with multiple sclerosis also found that intranasal insulin was well-tolerated, with no serious side effects compared to a placebo. Although the treatment did not consistently improve memory or thinking skills, no serious safety issues arose. This suggests that intranasal insulin could be a safe option for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for cognitive impairment?

Unlike the standard treatments for cognitive impairment, like cholinesterase inhibitors and memantine, intranasal insulin offers a unique approach. This treatment is administered through the nose using a nebulizer-like device, which could enhance insulin delivery directly to the brain, potentially improving memory and cognitive function. Researchers are excited about this method because it bypasses the blood-brain barrier more effectively than traditional methods, offering a promising new avenue for tackling cognitive decline.

What evidence suggests that this device is effective for cognitive impairment?

Research has shown that using insulin through a nasal spray might improve memory and thinking skills in people with Alzheimer's disease. Some studies found that small doses, like 20 IU, can boost memory and learning. This trial will test two different sequences: one group will receive insulin first, followed by a placebo, while the other group will receive a placebo first, followed by insulin. This method delivers insulin directly to the brain, which might benefit people with brain disorders. However, not all studies agree, and some found no major improvements in people with mild memory problems. Overall, while results are mixed, evidence suggests that nasal insulin could aid memory and learning. ^{1 4 5 6 7}

Who Is on the Research Team?

Suzanne Craft

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for individuals with mild cognitive impairment or normal cognition, stable health, and medication use. Participants must have normal lab values or non-significant abnormalities, speak English fluently, and not be pregnant. Excluded are those with regular alcohol/drug use, significant stroke history, any diabetes type, recent insulin/anti-diabetic drugs usage, seizures in the last five years, nursing home residents, investigational drug users within two months prior to screening visit.

Inclusion Criteria

My medications have been the same for the last 4 weeks.

Fluent in English

Cognitively normal or diagnosis of aMCI

Exclusion Criteria

Residence in a skilled nursing facility at screening

I have diabetes, whether I use insulin or not.

Pregnancy or possible pregnancy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either insulin or placebo administered intranasally using a nebulizer-like device

2 visits

2 visits (in-person)

Follow-up

Participants are monitored for changes in CSF insulin levels, AD biomarkers, and memory performance

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Intranasal Insulin

Trial Overview

The study tests a nasal device delivering insulin to see if it affects memory and other cognitive functions. It compares the effects of insulin versus placebo administered through an intranasal nebulizer-like device on participants' memory performance as well as blood and cerebral spinal fluid markers.

How Is the Trial Designed?

Group I: Placebo first, then insulin Experimental Treatment 3 Interventions

Participants will be randomly assigned to receive placebo administered with an intranasal nebulizer-like device. At visit 3 during second intervention period, participants in this arm will receive insulin.

Group II: Insulin first, then placebo Experimental Treatment 3 Interventions

Participants will be randomly assigned to receive regular insulin (U100, 20 IU) administered with an intranasal nebulizer-like device. Participants in this arm will then receive placebo at visit 3 during second intervention period.

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?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Published Research Related to This Trial

Intranasal insulin administration improved verbal memory, particularly story recall, in patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI), especially in those without the apoe4 gene variant, based on a systematic review of seven studies involving 293 patients.

The treatment was found to be safe with only minor adverse effects, suggesting that intranasal insulin could be a viable option for cognitive enhancement in AD or MCI, warranting further research with larger doses and better patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal insulin in Alzheimer's dementia or mild cognitive impairment: a systematic review. Avgerinos, KI., Kalaitzidis, G., Malli, 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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9512636/

Efficacy of intranasal insulin in improving cognition in mild ...

Based on our current study, there was no significant effects of intranasal insulin on the improvement of cognitive function in patients with MCI ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10411979/

Safety and efficacy of intranasal insulin in patients with ...

Intranasal insulin has shown promising results in treating patients with AD. The lower doses (20 IU) can play a positive role in improving the disease.

3.

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 ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S1878747925000595

Intranasal insulin for improving cognitive function in ...

Insulin administrated intranasally has shown to improve memory and learning in healthy people and in those with some neurodegenerative disorders. Hence, there ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01595646

Study of Nasal Insulin to Fight Forgetfulness - Long-acting ...

The study will examine the effects of intranasally administered long-acting insulin detemir on cognition in persons with Alzheimer's disease (AD) or amnestic ...

6.

jamanetwork.com

jamanetwork.com/journals/jamaneurology/fullarticle/1107947

Intranasal Insulin Therapy for Alzheimer Disease and ...

These results support longer trials of intranasal insulin therapy for patients with amnestic mild cognitive impairment and patients with AD.

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3260944/

Intranasal Insulin Therapy for Alzheimer Disease and ...

To examine the effects of intranasal insulin administration on cognition, function, cerebral glucose metabolism, and cerebrospinal fluid ...