Cognitive Impairment, Mild Cognitive Impairment
Conditions
Keywords
Intranasal Delivery of Insulin, Cognitive Testing, Nasal Insulin
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.
Interventions
DRUG20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company)
Participants will be assigned to receive regular insulin either 20 or 40 IU administered through an intranasal nebulizer-like device.
DRUG40 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company)
Participants will be assigned to receive regular insulin either 40 or 20 IU administered through an intranasal nebulizer-like device.
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Neither participants or site personnel will know which dose of insulin is being administered. Exceptions will be the study nurse who is directly involved in preparing the insulin.
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.
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cerebrospinal Fluid Insulin Levels | Baseline to 30 minutes after intervention administration | Change in cerebrospinal fluid insulin levels after receiving a 20 or 40 International Unit dose of insulin delivered with one of three devices |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Auditory-Verbal Learning Test | Post lumbar puncture | Memory performance measured with Auditory Verbal Learning Test after administration of 20 or 40 IU insulin. Memory measure in which participant hears a list of 12 words and is asked to recall them immediately after hearing them. Total possible score is 12 for delayed recall with higher number of words being better. |
| Cerebrospinal Fluid Levels of AB42 | 30 minutes after intervention administration | Cerebrospinal fluid levels of the 42 amino acid isoform of the beta amyloid peptide |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSuzanne Craft, PhD
Wake Forest University Health Sciences
Participant flow
Pre-assignment details
This feasibility study was initiated with the CPS and VP7 devices. Plans to test UDS device were discontinued. No participants were assigned to the UDS device arms.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 70.4 years |
| Education | 17.9 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Mini-mental state exam | 26 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 5 | 0 / 5 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 8 | 1 / 8 | 1 / 5 | 0 / 5 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 5 | 0 / 5 | 0 / 0 | 0 / 0 |
Outcome results
None listed