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SNIFF Multi-Device Study 2

Primary Purpose

Mild Cognitive Impairment, Cognitive Impairment

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company)
40 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company)
Sponsored by
Wake Forest University Health Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mild Cognitive Impairment focused on measuring Intranasal Delivery of Insulin, Cognitive Testing, Nasal Insulin

Eligibility Criteria

55 Years - 85 Years (Adult, Older Adult)All SexesAccepts 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

Sites / Locations

  • Wake Forest University Health Sciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

20 IU Insulin first, then 40 IU Insulin

40 IU Insulin first, then 20 IU Insulin

Arm 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.

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.

Outcomes

Primary Outcome Measures

CSF insulin levels
To compare changes in CSF insulin levels after receiving a 20 or 40 International Unit dose of insulin delivered with one of three devices, compared to baseline levels.

Secondary Outcome Measures

Auditory-Verbal Learning Test (AVLT)
To examine differences in memory performance measured with a list learning test (Auditory Verbal Learning Test) after administration of 20 or 40 IU insulin.

Full Information

First Posted
December 12, 2019
Last Updated
October 6, 2023
Sponsor
Wake Forest University Health Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT04199767
Brief Title
SNIFF Multi-Device Study 2
Official Title
SNIFF Multi-Device Study 2 - Study of Nasal Insulin to Fight Forgetfulness
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 16, 2020 (Actual)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
October 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Cognitive Impairment, Cognitive Impairment
Keywords
Intranasal Delivery of Insulin, Cognitive Testing, Nasal Insulin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
20 IU Insulin first, then 40 IU Insulin
Arm Type
Experimental
Arm 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.
Arm Title
40 IU Insulin first, then 20 IU Insulin
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company)
Other Intervention Name(s)
Humulin® R U-100
Intervention Description
Participants will be assigned to receive regular insulin either 20 or 40 IU administered through an intranasal nebulizer-like device.
Intervention Type
Drug
Intervention Name(s)
40 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly & Company)
Other Intervention Name(s)
Humulin® R U-100
Intervention Description
Participants will be assigned to receive regular insulin either 40 or 20 IU administered through an intranasal nebulizer-like device.
Primary Outcome Measure Information:
Title
CSF insulin levels
Description
To compare changes in CSF insulin levels after receiving a 20 or 40 International Unit dose of insulin delivered with one of three devices, compared to baseline levels.
Time Frame
30 minutes after intervention administration
Secondary Outcome Measure Information:
Title
Auditory-Verbal Learning Test (AVLT)
Description
To examine differences in memory performance measured with a list learning test (Auditory Verbal Learning Test) after administration of 20 or 40 IU insulin.
Time Frame
5 minutes before lumbar puncture, and immediately following lumbar puncture.
Other Pre-specified Outcome Measures:
Title
CSF Levels of AB42
Description
Levels of the 42 amino acid isoform of the beta amyloid peptide
Time Frame
30 minutes after intervention administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Suzanne Craft, PhD
Organizational Affiliation
Wake Forest University Health Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
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SNIFF Multi-Device Study 2

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