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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The SNIFF Device study will involve using a device to administer insulin through each participant's nose or intra-nasally. Insulin is a hormone that is produced in the body. It works by lowering levels of glucose (sugar) in the blood. This study is measuring how much insulin the device delivers. In addition, this study will look at the effects of insulin or placebo administered intra-nasally using a nebulizer-like device on memory, blood, and cerebral spinal fluid.

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 data supports the effectiveness of the drug intranasal insulin for cognitive impairment?

Research shows that intranasal insulin, including long-acting forms like insulin detemir, can improve memory in adults with mild cognitive impairment or early-stage Alzheimer's disease. Studies have found that it enhances memory and may reduce harmful brain changes associated with Alzheimer's. ^{1 2 3 4 5}

Is nasal insulin safe for humans?

Nasal insulin has been studied in people with Alzheimer's disease and mild cognitive impairment, and it is considered a safe alternative to intravenous insulin. Studies have shown it can improve memory without significant safety concerns. ^{1 2 3 4 6}

How is intranasal insulin different from other drugs for cognitive impairment?

Intranasal insulin is unique because it is administered through the nose, allowing it to directly affect the brain and improve memory in people with mild cognitive impairment or early Alzheimer's disease. Unlike other treatments, it uses insulin analogues like detemir, which have a longer-lasting effect, potentially offering more sustained cognitive benefits. ^{1 2 3 4 5}

Research Team

Suzanne Craft

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

References

1. 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]

2. 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]

3. 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]

4. Germany pubmed.ncbi.nlm.nih.gov

Intranasal insulin in Alzheimer's dementia or mild cognitive impairment: a systematic review. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

A feasibility study of the combination of intranasal insulin with dulaglutide for cognition in older adults with metabolic syndrome at high dementia risk - Study rationale and design. [2023]

6. 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]