Trial Outcomes & Findings for Study of Nasal Insulin to Fight Forgetfulness - Device Study (NCT NCT03857321)

Last Updated: 2025-10-31

Results Overview

Levels of insulin in cerebrospinal 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)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

30 minutes after intervention administration

Results posted on

2025-10-31

Participant Flow

The insulin-placebo/placebo-insulin sequence is a critical component of the study. It was counterbalanced in order to address potential practice effects for the Auditory-Verbal Learning Test (AVLT).

Participant milestones

Participant milestones
Measure	Insulin First, Then Placebo Participants in one group will receive regular insulin administered with an intranasal nebulizer-like device and will crossover to placebo for the second half of the trial. Participants in the other group will receive placebo first and crossover to insulin for the second half of the trail. Crossover occurs at visit 3. The insulin-placebo/placebo-insulin sequence is a critical component of the study. It was counterbalanced in order to address potential practice effects for the Auditory-Verbal Learning Test (AVLT). It is well known that memory test scores are lower the first time the test is taken, and then are higher the second time. The phenomenon is known as the practice effect. They are higher the second time because participants have been exposed to the memory stimuli previously. Thus if placebo is always administered first and insulin second, it may appear that the memory scores have improved due to the insulin, when the improvement is due instead to practice effects. Insulin: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly \& Company) Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100	Placebo First, Then Insulin Participants in one group will receive regular insulin administered with an intranasal nebulizer-like device and will crossover to placebo for the second half of the trial. Participants in the other group will receive placebo first and crossover to insulin for the second half of the trail. Crossover occurs at visit 3. The insulin-placebo/placebo-insulin sequence is a critical component of the study. It was counterbalanced in order to address potential practice effects for the Auditory-Verbal Learning Test (AVLT). It is well known that memory test scores are lower the first time the test is taken, and then are higher the second time. The phenomenon is known as the practice effect. They are higher the second time because participants have been exposed to the memory stimuli previously. Thus if placebo is always administered first and insulin second, it may appear that the memory scores have improved due to the insulin, when the improvement is due instead to practice effects. Insulin: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly \& Company) Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100
Overall Study STARTED	11	9
Overall Study COMPLETED	11	9
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Nasal Insulin to Fight Forgetfulness - Device Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=20 Participants Participants in one group will receive regular insulin administered with an intranasal nebulizer-like device and will crossover to placebo for the second half of the trial. Participants in the other group will receive placebo first and crossover to insulin for the second half of the trail. Crossover occurs at visit 3. Insulin: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly \& Company) Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100
Age, Continuous	67.8 years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 30 minutes after intervention administration

Population: The insulin-placebo/placebo-insulin sequence is a critical component of the study. The order was counterbalanced to address a phenomenon known as Practice Effect when giving the AVLT. When memory test are given a second time scores are higher because participants have been exposed to the memory stimuli previously. Thus if placebo is always given first and insulin second, it may appear that the memory scores have improved due to the insulin when the improvement is due instead to Practice Effects.

Outcome measures

Outcome measures
Measure	Insulin First, Then Placebo n=11 Participants 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: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly \& Company) Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100 intranasal nebulizer-like device: Participants will be assigned to receive placebo or regular insulin (U100, 20 IU) administered through an intranasal nebulizer-like device.	Placebo First, Then Insulin n=9 Participants 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: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly \& Company) Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100 intranasal nebulizer-like device: Participants will be assigned to receive placebo or regular insulin (U100, 20 IU) administered through an intranasal nebulizer-like device.
CSF Insulin Levels First Intervention	0.14 microUnits/mL Interval 0.01 to 0.26	—
CSF Insulin Levels Second Intervention	—	0.15 microUnits/mL Interval 0.06 to 0.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Insulin First, Then Placebo n=10 Participants 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: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly \& Company) Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100 intranasal nebulizer-like device: Participants will be assigned to receive placebo or regular insulin (U100, 20 IU) administered through an intranasal nebulizer-like device.	Placebo First, Then Insulin n=9 Participants 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: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly \& Company) Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100 intranasal nebulizer-like device: Participants will be assigned to receive placebo or regular insulin (U100, 20 IU) administered through an intranasal nebulizer-like device.
The Auditory-Verbal Learning Test (AVLT) First Intervention 5 minutes before lumbar puncture	7.1 average words recalled Interval 4.6 to 10.4	—
The Auditory-Verbal Learning Test (AVLT) First Intervention Immediately following lumbar puncture	4.9 average words recalled Interval 0.0 to 9.0	—
The Auditory-Verbal Learning Test (AVLT) Second Intervention 5 minutes before lumbar puncture	—	9.4 average words recalled Interval 5.2 to 11.6
The Auditory-Verbal Learning Test (AVLT) Second Intervention Immediately following lumbar puncture	—	8.9 average words recalled Interval 3.0 to 14.0

SECONDARY outcome

Timeframe: 30 minutes after intervention administration

Levels of the 42 amino acid isoform of the beta amyloid peptide

Outcome measures

Outcome measures
Measure	Insulin First, Then Placebo n=11 Participants 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: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly \& Company) Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100 intranasal nebulizer-like device: Participants will be assigned to receive placebo or regular insulin (U100, 20 IU) administered through an intranasal nebulizer-like device.	Placebo First, Then Insulin n=9 Participants 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: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly \& Company) Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100 intranasal nebulizer-like device: Participants will be assigned to receive placebo or regular insulin (U100, 20 IU) administered through an intranasal nebulizer-like device.
CSF Levels of AB42 Insulin first, then placebo	524.5 pg/ml Interval 207.0 to 1086.5	—
CSF Levels of AB42 Placebo first, then insulin	—	536 pg/ml Interval 244.0 to 757.5

SECONDARY outcome

Timeframe: 30 minutes after intervention administration

Levels of the tau protein

Outcome measures

Outcome measures
Measure	Insulin First, Then Placebo n=11 Participants 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: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly \& Company) Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100 intranasal nebulizer-like device: Participants will be assigned to receive placebo or regular insulin (U100, 20 IU) administered through an intranasal nebulizer-like device.	Placebo First, Then Insulin n=9 Participants 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: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly \& Company) Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100 intranasal nebulizer-like device: Participants will be assigned to receive placebo or regular insulin (U100, 20 IU) administered through an intranasal nebulizer-like device.
CSF Levels of Total Tau Insulin first, then placebo	431.4 pg/ml Interval 126.0 to 880.5	—
CSF Levels of Total Tau Placebo first, then insulin	—	267.3 pg/ml Interval 125.5 to 687.0

SECONDARY outcome

Timeframe: 30 minutes after intervention administration

Levels of the tau phosphorylated at isotope 181

Outcome measures

Outcome measures
Measure	Insulin First, Then Placebo n=11 Participants 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: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly \& Company) Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100 intranasal nebulizer-like device: Participants will be assigned to receive placebo or regular insulin (U100, 20 IU) administered through an intranasal nebulizer-like device.	Placebo First, Then Insulin n=9 Participants 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: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly \& Company) Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100 intranasal nebulizer-like device: Participants will be assigned to receive placebo or regular insulin (U100, 20 IU) administered through an intranasal nebulizer-like device.
CSF Levels Phospho-tau 181 Insulin first, then placebo	61.5 pg/ml Interval 21.0 to 107.3	—
CSF Levels Phospho-tau 181 Placebo first, then insulin	—	40.6 pg/ml Interval 20.4 to 109.0

Adverse Events

Insulin

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Insulin n=20 participants at risk Participants will be randomly assigned to receive regular insulin (U100, 20 IU) administered with an intranasal nebulizer-like device. Insulin: 20 IU Humulin® R U-100 (NDC: 0002-8215, Eli Lilly \& Company) intranasal nebulizer-like device: Participants will be assigned to receive placebo or regular insulin (U100, 20 IU) administered through an intranasal nebulizer-like device.	Placebo n=20 participants at risk Participants will be randomly assigned to receive placebo administered with an intranasal nebulizer-like device. Placebo: Matching placebo (sterile saline) to 20 IU Humulin® R U-100 intranasal nebulizer-like device: Participants will be assigned to receive placebo or regular insulin (U100, 20 IU) administered through an intranasal nebulizer-like device.
Nervous system disorders vasovagal episode	5.0% 1/20 • Number of events 1 • Up to Week 6	0.00% 0/20 • Up to Week 6
Musculoskeletal and connective tissue disorders low back discomfort	5.0% 1/20 • Number of events 1 • Up to Week 6	0.00% 0/20 • Up to Week 6
General disorders tired	5.0% 1/20 • Number of events 1 • Up to Week 6	0.00% 0/20 • Up to Week 6
Skin and subcutaneous tissue disorders rash	5.0% 1/20 • Number of events 1 • Up to Week 6	0.00% 0/20 • Up to Week 6

Additional Information

Suzanne Craft, PhD

Atrium Health Wake Forest

Phone: 336-713-8846

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place