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

• ClinicalTrials.gov Identifier: NCT01595646
• Recruitment Status: Completed
• First Posted: May 10, 2012
• Results First Posted: February 1, 2018
• Last Update Posted: November 17, 2020
• Sponsor: Wake Forest University Health Sciences
• Collaborator: Alzheimer's Association
• Information provided by (Responsible Party): Wake Forest University Health Sciences

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Alzheimer's Disease; Mild Cognitive Impairment
• Interventions: Drug: Saline; Drug: Insulin detemir; Drug: Insulin
• Enrollment: 37

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Saline	Insulin Detemir	Insulin
Arm/Group Description	Saline: Saline, administered intranasally twice per day for a 16 week duration	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)	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)
Period Title: Overall Study
Started	13	12	12
Completed	12	12	12
Not Completed	1	0	0
Reason Not Completed
Withdrawal by Subject	1	0	0

Baseline Characteristics

Arm/Group Title		Saline	Insulin Detemir	Insulin	Total
Arm/Group Description		Saline: Saline, administered intranasally twice per day for a 16 week duration	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)	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 of all reporting groups
Overall Number of Baseline Participants		12	12	12	36
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	12 participants	12 participants	36 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	4 33.3%	4 33.3%	3 25.0%	11 30.6%
	>=65 years	8 66.7%	8 66.7%	9 75.0%	25 69.4%
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	12 participants	12 participants	12 participants	36 participants
		68; (61 to 75)	66; (62 to 70)	68; (56 to 80)	68; (56 to 80)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	12 participants	12 participants	36 participants
	Female	6 50.0%	6 50.0%	7 58.3%	19 52.8%
	Male	6 50.0%	6 50.0%	5 41.7%	17 47.2%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	12 participants	12 participants	36 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	White	12 100.0%	12 100.0%	12 100.0%	36 100.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Verbal Memory Composite
Description	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.
Time Frame	Change from Baseline in Verbal Memory at 16 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Saline	Insulin Detemir	Insulin
Arm/Group Description:	Saline: Saline, administered intranasally twice per day for a 16 week duration	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)	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 Number of Participants Analyzed	12	12	12
Mean (Standard Error); Unit of Measure: Change in Z score memory composite
	-.31247583 (.23)	.33390008 (.23)	-.05181561 (.22)

2. Secondary Outcome

Title	Cerebral Spinal Fluid (CSF) Biomarkers of AD
Description	CSF Abeta (Abeta 42) and Tau (total tau and phosphorylated tau) will be measured in each subject.
Time Frame	Change from Baseline in CSF Biomarkers at 16 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Saline	Insulin Detemir	Insulin
Arm/Group Description:	Saline: Saline, administered intranasally twice per day for a 16 week duration	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)	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 Number of Participants Analyzed	12	12	12
Mean (Standard Deviation); Unit of Measure: pg/mL
Abeta42 Pre	331.5 (148.4)	408.5 (196.9)	305.5 (86.1)
Abeta 42 Post	384 (212)	381.8 (227.8)	325 (92.1)
Tau Pre	109.7 (27)	118.3 (49.1)	132.3 (71)
Tau Post	117.1 (36.8)	107.6 (56)	152.2 (106.7)
Tau-P181 Pre	65.1 (33.1)	63.9 (28)	74 (28.9)
Tau-P181 Post	72.17 (25.3)	64.1 (19.8)	68.5 (39.7)

3. Secondary Outcome

Title	Cerebral Spinal Fluid (CSF) Biomarkers of AD TTau-P181/Abeta42 Ratio
Description	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.
Time Frame	Change from Baseline in CSF Biomarkers at 16 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Saline	Insulin Detemir	Insulin
Arm/Group Description:	Saline: Saline, administered intranasally twice per day for a 16 week duration	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)	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 Number of Participants Analyzed	12	12	12
Mean (Standard Deviation); Unit of Measure: ratio
TTau-P181/Abeta42 ratio Pre	.27 (19)	.23 (.22)	.27 (.14)
Tau-P181/Abeta42 ratio Post	.30 (.21)	.23 (.16)	.23 (.13)

4. Secondary Outcome

Title	Functional Ability
Description	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.
Time Frame	baseline, month 2, and month 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Saline	Insulin Detemir	Insulin
Arm/Group Description:	Saline placebo taken twice per day via intranasal route. Saline: Saline, administered intranasally twice per day for a 16 week duration	20IU of Insulin Detemir taken twice per day (40IU total per day) via intranasal route Insulin detemir: 20IU of insulin detemir, administered intranasally twice per day for a 16 week duration (total of 40IU insulin detemir per day)	20IU Insulin, administered twice per day (40IU total per day) via intranasal route Insulin: 20IU insulin, administered intranasally twice per day for a 16 week duration (total of 40IU insulin per day)
Overall Number of Participants Analyzed	12	12	12
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	7.3 (6.9)	8.7 (6.7)	7.7 (6.8)
month 2	7 (6.7)	9.7 (7.3)	9.7 (7.4)
month 4	6.9 (7.1)	9.1 (7.5)	10.6 (9.4)

5. Secondary Outcome

Title	The Alzheimer's Disease Assessment Scale-Cognitive [ADAS-Cog/Alzheimer's Disease Cooperative Study (ADCS)] - MCI Revision
Description	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.
Time Frame	Baseline, Month 2 and Month 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Saline	Insulin Detemir	Insulin
Arm/Group Description:	Saline placebo taken twice per day via intranasal route. Saline: Saline, administered intranasally twice per day for a 16 week duration	20IU of Insulin Detemir taken twice per day (40IU total per day) via intranasal route Insulin detemir: 20IU of insulin detemir, administered intranasally twice per day for a 16 week duration (total of 40IU insulin detemir per day)	20IU Insulin, administered twice per day (40IU total per day) via intranasal route Insulin: 20IU insulin, administered intranasally twice per day for a 16 week duration (total of 40IU insulin per day)
Overall Number of Participants Analyzed	12	12	12
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	20 (11.7)	21.6 (13.7)	19.8 (12.8)
Month 2	18.5 (11.8)	23.4 (17.1)	21.8 (13.6)
Month 4	20.4 (13.7)	19.5 (12.9)	22.6 (15.8)

6. Other Pre-specified Outcome

Title	Executive Function Composite
Description	Sum of Z Scores from Dot Counting Test (test of executive functioning) and Benton Visual Retention Test Form F&G (a test of visual working memory)
Time Frame	Change from Baseline in Executive Functioning at 16 Weeks

Outcome Measure Data Not Reported

7. Other Pre-specified Outcome

Title	Plasma Biomarkers of AD
Description	Plasma Abeta (ABeta 38, ABeta 40, and Abeta 42) and Tau (total tau and phosphorylated tau) will be measured in each subject.
Time Frame	Change from Baseline in Plasma Biomarkers at 16 Weeks

Outcome Measure Data Not Reported

8. Other Pre-specified Outcome

Title	Cerebral Blood Flow
Description	Functional MRI and arterial-spin labeling perfusion MRI
Time Frame	Change from Baseline in Cerebral Blood Flow at 16 Weeks

Outcome Measure Data Not Reported

9. Other Pre-specified Outcome

Title	Glucose Tolerance
Description	Subjects will undergo oral glucose tolerance test (OGTT) to assess glucose tolerance
Time Frame	Change from Baseline in Glucose Tolerance at 16 Weeks

Outcome Measure Data Not Reported

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Saline		Insulin Detemir		Insulin
Arm/Group Description	Saline: Saline, administered intranasally twice per day for a 16 week duration		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)		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)
All-Cause Mortality
	Saline		Insulin Detemir		Insulin
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/12 (0.00%)		0/12 (0.00%)		0/12 (0.00%)
Serious Adverse Events
	Saline		Insulin Detemir		Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0.00%)		0/12 (0.00%)		0/12 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Saline		Insulin Detemir		Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/12 (33.33%)		0/12 (0.00%)		0/12 (0.00%)
Cardiac disorders
Chest pain † [1]	1/12 (8.33%)	1	0/12 (0.00%)	0	0/12 (0.00%)	0
General disorders
Congestion † [2]	1/12 (8.33%)	1	0/12 (0.00%)	0	0/12 (0.00%)	0
Cold & Flu Symptoms † [3]	1/12 (8.33%)	1	0/12 (0.00%)	0	0/12 (0.00%)	0
Nervous system disorders
Anxiety † [4]	1/12 (8.33%)	1	0/12 (0.00%)	0	0/12 (0.00%)	0
† Indicates events were collected by systematic assessment; [1] PT experienced chest pain during MRI.; [2] PT reported head congestion.; [3] PT reported having symptoms resembling a cold or flu.; [4] PT began to feel some anxiety during the MRI scan.

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Suzanne Craft, PhD
• Organization: Wake Forest School of Medicine
• Phone: 3366-713-8830
• EMail: suzcraft@wakehealth.edu

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT01595646
• Other Study ID Numbers: IRB00023230; ZEN-10-173646US ( Other Grant/Funding Number: Alzheimer's Association )
• First Submitted: May 8, 2012
• First Posted: May 10, 2012
• Results First Submitted: April 17, 2017
• Results First Posted: February 1, 2018
• Last Update Posted: November 17, 2020