Clinical trial NCT04199767: SNIFF Multi-Device Study 2
Official title: SNIFF Multi-Device Study 2 - Study of Nasal Insulin to Fight Forgetfulness
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Mild Cognitive Impairment
Cognitive Impairment
Keywords: Intranasal Delivery of Insulin
Cognitive Testing
Nasal Insulin
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2019-12-16
Enrollment: 30
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: At study entry, participants will be randomized to receive either 20 or 40 International Units of insulin first and the opposite substance on a second visit.
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Eligibility criteria: 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

Primary outcomes:
measure: CSF insulin levels
timeFrame: 30 minutes after intervention administration
Secondary outcomes:
measure: Auditory-Verbal Learning Test (AVLT)
timeFrame: 5 minutes before lumbar puncture, and immediately following lumbar puncture.
Other outcomes:
measure: CSF Levels of AB42
timeFrame: 30 minutes after intervention administration
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Suzanne Craft, PhD
role: PRINCIPAL_INVESTIGATOR
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