Trial Outcomes & Findings for Study of Nasal Insulin to Fight Forgetfulness - Long-acting Insulin Detemir

Results Overview

The composite will consist of the sum of Z scores for Delayed Story Recall and Buschke Selective Reminding Test. In the Story Recall test subjects listen to a story containing 44 informational bits that is read once. Subjects will be asked to recall the story immediately after the reading and after a 20-min delay. Credit is awarded for each bit recalled verbatim or accurately paraphrased. The Buschke Selective Reminding Test measures verbal memory through multiple trials of a list learning task. A list of 12 words is audibly presented to the subject, and subjects recall as many words as possible. On subsequent trials, subjects are only told those words they omitted on the previous trial. The procedure continues until the subject recalls all words on two successive trials or to the twelfth trial. After a 30-minute delay, subjects recall as many items as possible. Number of items recalled after the delay will be summed. Higher scores indicate better performance.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

37 participants

Primary outcome timeframe

Change from Baseline in Verbal Memory at 16 weeks

Results posted on

2020-11-17

Participant Flow

Participant milestones

Participant milestones
Measure	Saline Saline: Saline, administered intranasally twice per day for a 16 week duration	Insulin Detemir 20IU of Insulin Detemir taken twice per day (40IU total per day) Insulin detemir: 20IU of insulin detemir, administered intranasally twice per day for a 16 week duration (total of 40IU insulin detemir per day)	Insulin 20IU Insulin, administered twice per day (40IU total per day) Insulin: 20IU insulin, administered intranasally twice per day for a 16 week duration (total of 40IU insulin per day)
Overall Study STARTED	13	12	12
Overall Study COMPLETED	12	12	12
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Saline Saline: Saline, administered intranasally twice per day for a 16 week duration	Insulin Detemir 20IU of Insulin Detemir taken twice per day (40IU total per day) Insulin detemir: 20IU of insulin detemir, administered intranasally twice per day for a 16 week duration (total of 40IU insulin detemir per day)	Insulin 20IU Insulin, administered twice per day (40IU total per day) Insulin: 20IU insulin, administered intranasally twice per day for a 16 week duration (total of 40IU insulin per day)
Overall Study Withdrawal by Subject	1	0	0

Baseline Characteristics

Study of Nasal Insulin to Fight Forgetfulness - Long-acting Insulin Detemir - 120 Days (SL120)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Saline n=12 Participants Saline: Saline, administered intranasally twice per day for a 16 week duration	Insulin Detemir n=12 Participants 20IU of Insulin Detemir taken twice per day (40IU total per day) Insulin detemir: 20IU of insulin detemir, administered intranasally twice per day for a 16 week duration (total of 40IU insulin detemir per day)	Insulin n=12 Participants 20IU Insulin, administered twice per day (40IU total per day) Insulin: 20IU insulin, administered intranasally twice per day for a 16 week duration (total of 40IU insulin per day)	Total n=36 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	11 Participants n=4 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants	8 Participants n=7 Participants	9 Participants n=5 Participants	25 Participants n=4 Participants
Age, Continuous	68 years n=5 Participants	66 years n=7 Participants	68 years n=5 Participants	68 years n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	19 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	17 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	36 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Change from Baseline in Verbal Memory at 16 weeks

Population: The study is in data analysis and manuscript write-up.

The composite will consist of the sum of Z scores for Delayed Story Recall and Buschke Selective Reminding Test. In the Story Recall test subjects listen to a story containing 44 informational bits that is read once. Subjects will be asked to recall the story immediately after the reading and after a 20-min delay. Credit is awarded for each bit recalled verbatim or accurately paraphrased. The Buschke Selective Reminding Test measures verbal memory through multiple trials of a list learning task. A list of 12 words is audibly presented to the subject, and subjects recall as many words as possible. On subsequent trials, subjects are only told those words they omitted on the previous trial. The procedure continues until the subject recalls all words on two successive trials or to the twelfth trial. After a 30-minute delay, subjects recall as many items as possible. Number of items recalled after the delay will be summed. Higher scores indicate better performance.

Outcome measures

Outcome measures
Measure	Saline n=12 Participants Saline: Saline, administered intranasally twice per day for a 16 week duration	Insulin Detemir n=12 Participants 20IU of Insulin Detemir taken twice per day (40IU total per day) Insulin detemir: 20IU of insulin detemir, administered intranasally twice per day for a 16 week duration (total of 40IU insulin detemir per day)	Insulin n=12 Participants 20IU Insulin, administered twice per day (40IU total per day) Insulin: 20IU insulin, administered intranasally twice per day for a 16 week duration (total of 40IU insulin per day)
Verbal Memory Composite	-.31247583 Change in Z score memory composite Standard Error .23	.33390008 Change in Z score memory composite Standard Error .23	-.05181561 Change in Z score memory composite Standard Error .22

SECONDARY outcome

Timeframe: Change from Baseline in CSF Biomarkers at 16 Weeks

CSF Abeta (Abeta 42) and Tau (total tau and phosphorylated tau) will be measured in each subject.

Outcome measures

Outcome measures
Measure	Saline n=12 Participants Saline: Saline, administered intranasally twice per day for a 16 week duration	Insulin Detemir n=12 Participants 20IU of Insulin Detemir taken twice per day (40IU total per day) Insulin detemir: 20IU of insulin detemir, administered intranasally twice per day for a 16 week duration (total of 40IU insulin detemir per day)	Insulin n=12 Participants 20IU Insulin, administered twice per day (40IU total per day) Insulin: 20IU insulin, administered intranasally twice per day for a 16 week duration (total of 40IU insulin per day)
Cerebral Spinal Fluid (CSF) Biomarkers of AD Tau Post	117.1 pg/mL Standard Deviation 36.8	107.6 pg/mL Standard Deviation 56	152.2 pg/mL Standard Deviation 106.7
Cerebral Spinal Fluid (CSF) Biomarkers of AD Abeta42 Pre	331.5 pg/mL Standard Deviation 148.4	408.5 pg/mL Standard Deviation 196.9	305.5 pg/mL Standard Deviation 86.1
Cerebral Spinal Fluid (CSF) Biomarkers of AD Abeta 42 Post	384 pg/mL Standard Deviation 212	381.8 pg/mL Standard Deviation 227.8	325 pg/mL Standard Deviation 92.1
Cerebral Spinal Fluid (CSF) Biomarkers of AD Tau Pre	109.7 pg/mL Standard Deviation 27	118.3 pg/mL Standard Deviation 49.1	132.3 pg/mL Standard Deviation 71
Cerebral Spinal Fluid (CSF) Biomarkers of AD Tau-P181 Pre	65.1 pg/mL Standard Deviation 33.1	63.9 pg/mL Standard Deviation 28	74 pg/mL Standard Deviation 28.9
Cerebral Spinal Fluid (CSF) Biomarkers of AD Tau-P181 Post	72.17 pg/mL Standard Deviation 25.3	64.1 pg/mL Standard Deviation 19.8	68.5 pg/mL Standard Deviation 39.7

SECONDARY outcome

Timeframe: Change from Baseline in CSF Biomarkers at 16 Weeks

CSF Abeta (ABeta 38, ABeta 40, and Abeta 42) and Tau (total tau and phosphorylated tau) will be measured in each subject. A pre and post ratio of TTau-P181/Abeta42 will be given.

Outcome measures

Outcome measures
Measure	Saline n=12 Participants Saline: Saline, administered intranasally twice per day for a 16 week duration	Insulin Detemir n=12 Participants 20IU of Insulin Detemir taken twice per day (40IU total per day) Insulin detemir: 20IU of insulin detemir, administered intranasally twice per day for a 16 week duration (total of 40IU insulin detemir per day)	Insulin n=12 Participants 20IU Insulin, administered twice per day (40IU total per day) Insulin: 20IU insulin, administered intranasally twice per day for a 16 week duration (total of 40IU insulin per day)
Cerebral Spinal Fluid (CSF) Biomarkers of AD TTau-P181/Abeta42 Ratio TTau-P181/Abeta42 ratio Pre	.27 ratio Standard Deviation 19	.23 ratio Standard Deviation .22	.27 ratio Standard Deviation .14
Cerebral Spinal Fluid (CSF) Biomarkers of AD TTau-P181/Abeta42 Ratio Tau-P181/Abeta42 ratio Post	.30 ratio Standard Deviation .21	.23 ratio Standard Deviation .16	.23 ratio Standard Deviation .13

SECONDARY outcome

Timeframe: baseline, month 2, and month 4

Subjects will have a collateral informant (i.e., spouse or friend) rate the subjects' ability to carry out activities of daily living on the Dementia Severity Rating Scale. The Dementia Severity Rating Scale is made up of sub-scales and the scores from each are summed to produce one score. The scale assess memory, ability to get from place to place, and speech and language each with a range from 0-6; recognition of family members and social and community both having a range from 0-5; orientation of time, orientation to place, ability to make decisions, home activities and responsibilities, and control of urination and bowels each having a range of 0-4; personal care- cleanliness and eating both with a range of 0-3. The total score range is from 0-54 and lower scores denotes better outcomes.

Outcome measures

Outcome measures
Measure	Saline n=12 Participants Saline: Saline, administered intranasally twice per day for a 16 week duration	Insulin Detemir n=12 Participants 20IU of Insulin Detemir taken twice per day (40IU total per day) Insulin detemir: 20IU of insulin detemir, administered intranasally twice per day for a 16 week duration (total of 40IU insulin detemir per day)	Insulin n=12 Participants 20IU Insulin, administered twice per day (40IU total per day) Insulin: 20IU insulin, administered intranasally twice per day for a 16 week duration (total of 40IU insulin per day)
Functional Ability Baseline	7.3 units on a scale Standard Deviation 6.9	8.7 units on a scale Standard Deviation 6.7	7.7 units on a scale Standard Deviation 6.8
Functional Ability month 2	7 units on a scale Standard Deviation 6.7	9.7 units on a scale Standard Deviation 7.3	9.7 units on a scale Standard Deviation 7.4
Functional Ability month 4	6.9 units on a scale Standard Deviation 7.1	9.1 units on a scale Standard Deviation 7.5	10.6 units on a scale Standard Deviation 9.4

SECONDARY outcome

Timeframe: Baseline, Month 2 and Month 4

This cognitive screening measure contains measures of confrontational naming, following commands, constructional praxis, ideational praxis, orientation, and language production and comprehension. Total scores range from 0-70, with higher scores indicating greater cognitive impairment.

Outcome measures

Outcome measures
Measure	Saline n=12 Participants Saline: Saline, administered intranasally twice per day for a 16 week duration	Insulin Detemir n=12 Participants 20IU of Insulin Detemir taken twice per day (40IU total per day) Insulin detemir: 20IU of insulin detemir, administered intranasally twice per day for a 16 week duration (total of 40IU insulin detemir per day)	Insulin n=12 Participants 20IU Insulin, administered twice per day (40IU total per day) Insulin: 20IU insulin, administered intranasally twice per day for a 16 week duration (total of 40IU insulin per day)
The Alzheimer's Disease Assessment Scale-Cognitive [ADAS-Cog/Alzheimer's Disease Cooperative Study (ADCS)] - MCI Revision Baseline	20 units on a scale Standard Deviation 11.7	21.6 units on a scale Standard Deviation 13.7	19.8 units on a scale Standard Deviation 12.8
The Alzheimer's Disease Assessment Scale-Cognitive [ADAS-Cog/Alzheimer's Disease Cooperative Study (ADCS)] - MCI Revision Month 2	18.5 units on a scale Standard Deviation 11.8	23.4 units on a scale Standard Deviation 17.1	21.8 units on a scale Standard Deviation 13.6
The Alzheimer's Disease Assessment Scale-Cognitive [ADAS-Cog/Alzheimer's Disease Cooperative Study (ADCS)] - MCI Revision Month 4	20.4 units on a scale Standard Deviation 13.7	19.5 units on a scale Standard Deviation 12.9	22.6 units on a scale Standard Deviation 15.8

OTHER_PRE_SPECIFIED outcome

Timeframe: Change from Baseline in Executive Functioning at 16 Weeks

Other events: 0 other events

Deaths: 0 deaths

Insulin

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	Saline n=12 participants at risk Saline: Saline, administered intranasally twice per day for a 16 week duration	Insulin Detemir n=12 participants at risk 20IU of Insulin Detemir taken twice per day (40IU total per day) Insulin detemir: 20IU of insulin detemir, administered intranasally twice per day for a 16 week duration (total of 40IU insulin detemir per day)	Insulin n=12 participants at risk 20IU Insulin, administered twice per day (40IU total per day) Insulin: 20IU insulin, administered intranasally twice per day for a 16 week duration (total of 40IU insulin per day)
Cardiac disorders Chest pain	8.3% 1/12 • Number of events 1	0.00% 0/12	0.00% 0/12
Nervous system disorders Anxiety	8.3% 1/12 • Number of events 1	0.00% 0/12	0.00% 0/12
General disorders Congestion	8.3% 1/12 • Number of events 1	0.00% 0/12	0.00% 0/12
General disorders Cold & Flu Symptoms	8.3% 1/12 • Number of events 1	0.00% 0/12	0.00% 0/12

Additional Information

Suzanne Craft, PhD

Wake Forest School of Medicine

Phone: 3366-713-8830

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Trial Outcomes & Findings for Study of Nasal Insulin to Fight Forgetfulness - Long-acting Insulin Detemir - 120 Days (SL120) (NCT NCT01595646)

Results Overview

Participant Flow

Participant milestones

Reasons for withdrawal

Baseline Characteristics

Baseline characteristics by cohort

PRIMARY outcome

Outcome measures

SECONDARY outcome

Outcome measures

SECONDARY outcome

Outcome measures

SECONDARY outcome

Outcome measures

SECONDARY outcome

Outcome measures

OTHER_PRE_SPECIFIED outcome

Outcome measures

OTHER_PRE_SPECIFIED outcome

Outcome measures

OTHER_PRE_SPECIFIED outcome

Outcome measures

OTHER_PRE_SPECIFIED outcome

Outcome measures

Adverse Events

Saline

Insulin Detemir

Insulin

Serious adverse events

Other adverse events

Additional Information

Suzanne Craft, PhD

Results disclosure agreements