SNIFF Multi-Device Study 2

Wake Forest University (WFU)

Status and phase: Suspended; Phase 2

Conditions: Cognitive Impairment; Mild Cognitive Impairment

Treatments: Drug: 40 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company); Drug: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company)

Study type: Interventional

Funder types: Other

Identifiers

NCT04199767

IRB00062612

Details and patient eligibility

About

The SNIFF Device study will involve using one of three devices to administer insulin through each participant's nose or intra-nasally, accompanied by a lumbar puncture. This goal of this study is to measure how much insulin the device delivers to the cerebrospinal fluid (CSF). In addition, this study will look at the effects of insulin administered intra-nasally on memory, and on blood levels of insulin.

Full 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 40 International Units delivered with one of three nebulizer-like devices on CSF insulin levels, AD biomarkers and memory. At study entry, participants will be randomized to receive either 20 or 40 IU insulin first, and the opposite dose 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 establish which device and which dose provides the greatest increase in CSF insulin which will provide important evidence to be used in the design of future trials.

Enrollment: 30 estimated patients

Sex: All

Ages: 55 to 85 years old

Volunteers: Accepts Healthy Volunteers

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

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 regular use of insulin or any other anti-diabetic medication within 2 months of screening visit.
• 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, anti-parkinsonian medications, or any other exclusionary medications

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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30 participants in 2 patient groups

20 IU Insulin first, then 40 IU Insulin

Experimental group

Description:

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 regular insulin (U100, 40 IU) at visit 3 during second intervention period.

Treatment:

Drug: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company)

40 IU Insulin first, then 20 IU Insulin

Experimental group

Description:

Participants will be randomly assigned to receive regular insulin (U100, 40 IU) administered with an intranasal nebulizer-like device. Participants in this arm will then receive regular insulin (U100, 20 IU) at visit 3 during second intervention period.

Treatment:

Drug: 40 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company)