Study of Nasal Insulin to Fight Forgetfulness - Device Study

Phase 2

Active, not recruiting

• Conditions: Mild Cognitive Impairment; Cognitive Impairment
• Interventions: Drug: Insulin; Other: Placebo; Device: intranasal nebulizer-like device

• Registration Number: NCT03857321
• Lead Sponsor: Wake Forest University Health Sciences

Brief Summary

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.

Detailed Description

The aim of this study is to determine the ability of an intranasal delivery device to increase levels of insulin in cerebrospinal fluid (CSF).

A growing body of evidence suggests that insulin plays a role in normal memory processes and that insulin abnormalities may contribute to cognitive and brain changes associated with Alzheimer's disease (AD). Interestingly, insulin administered to the nasal cavity is transported within a few minutes into the brain, but does not affect blood sugar or insulin levels.

The study will consist of a single site, randomized, double-blind trial comparing the acute effects of INI (20 International Units) or placebo delivered with nebulizer-like device on CSF insulin levels, AD biomarkers and memory. At study entry, participants will be randomized to receive either an acute dose of insulin or placebo first, and the other substance on a second visit. Participants who are cognitively normal or who have aMCI (n=30) will be enrolled. The primary outcome measure will be to test the hypothesis that CSF insulin levels will increase 30 minutes after receiving a 20 International Units dose of insulin delivered with a nebulizer-like device, compared to levels achieved 30 minutes after placebo.

Study Timeline

• Study First Submitted: 2019-02-22
• Study First Submitted QC: 2019-02-25
• Study First Posted: 2019-02-27
• Study Start: 2019-04-12
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-12
• Last Update Posted: 2023-12-13
• Primary Completion: 2025-08
• Study Completion: 2025-08

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Fluent in English
• Cognitively normal or diagnosis of aMCI
• Stable medical condition for 3 months prior to screening visit
• Stable medications for 4 weeks prior to the screening and study visits
• Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the study physician

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Exclusion Criteria

• A diagnosis of dementia
• History of a clinically significant stroke
• Current evidence or history in past two years of epilepsy, head injury with loss of consciousness, any major psychiatric disorder including psychosis, major depression, bipolar disorder
• Diabetes (type I or type II) insulin dependent and non-insulin dependent diabetes mellitus
• Current or past use of insulin or any other anti-diabetic medication within 5 years of Screening visit.
• History of cancer five years prior to screening (history of skin melanoma or stable prostate cancer are not exclusionary)
• History of seizure within past five years
• Pregnancy or possible pregnancy.
• Use of anticoagulants warfarin (Coumadin) and dabigatran (Pradaxa)
• Residence in a skilled nursing facility at screening
• Use of an investigational agent within two months of screening visit
• Regular use of alcohol, narcotics, anticonvulsants, antiparkinsonian medications, or any other exclusionary medications

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo first, then insulin	Placebo	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.
Insulin first, then placebo	Insulin	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.
Placebo first, then insulin	intranasal nebulizer-like device	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.
Insulin first, then placebo	Placebo	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.
Insulin first, then placebo	intranasal nebulizer-like device	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.
Placebo first, then insulin	Insulin	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.

Primary Outcome Measures

Name	Time	Method
CSF insulin levels	30 minutes after intervention administration	Levels of insulin in CS fluid after being delivered with the device. This will help to determine the ability of an intranasal delivery device to increase levels of insulin in cerebrospinal fluid (CSF)

Secondary Outcome Measures

Name	Time	Method
The Auditory-Verbal Learning Test (AVLT)	5 minutes before lumbar puncture, and immediately following lumbar puncture	memory measure in which participant hears a list of 12 words over 3 trials, and is asked to recall them immediately after hearing them, then again after a 45 minute delay. Total possible score is 36 for immediate recall and 12 for delayed recall. Higher scores are better.
CSF Levels of total tau	30 minutes after intervention administration	Levels of the tau protein
CSF Levels of AB42	30 minutes after intervention administration	Levels of the 42 amino acid isoform of the beta amyloid peptide
CSF Levels phospho-tau 181	30 minutes after intervention administration	Levels of the tau phosphorylated at isotope 181

Trial Locations

Locations (1)

Wake Forest University Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States