Trial Outcomes & Findings for Intranasal Glulisine in Amnestic Mild Cognitive Impairment and Probable Mild Alzheimer's Disease (NCT NCT02503501)

Last Updated: 2020-04-09

Results Overview

The ADAS-Cog was developed as an outcome measure for global cognition in clinical trials for Alzheimer's disease. The ADAS-Cog assesses multiple cognitive domains including memory, language, praxis, and orientation. The modified ADAS-Cog 13-item scale includes all original ADAS-Cog items with the addition of a number cancellation task and a delayed free recall task, for a total of 85 points (0: no cognitive impairment; 85: severe impairment).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

49 participants

Primary outcome timeframe

Baseline and 6 months

Results posted on

2020-04-09

Participant Flow

Of the 49 participants who signed a consent form for the study, 12 participants screen failed and did not meet the inclusion criteria at screening, 2 participants declined to participate after the initial screening. These 14 participants were not assigned to a treatment group since they were removed from the study prior to randomization.

Participant milestones

Participant milestones
Measure	Insulin Glulisine Insulin Glulisine 20 IU (0.1ml/10 units in each nostril) per intranasal dose, 2 times per day for 6 months Insulin glulisine	Placebo Saline 20 IU (0.1 ml in each nostril) per intranasal dose, 2 times per day for 6 months Placebo: Bacteriostatic 0.9% Sodium Chloride
Overall Study STARTED	19	16
Overall Study COMPLETED	18	13
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Insulin Glulisine Insulin Glulisine 20 IU (0.1ml/10 units in each nostril) per intranasal dose, 2 times per day for 6 months Insulin glulisine	Placebo Saline 20 IU (0.1 ml in each nostril) per intranasal dose, 2 times per day for 6 months Placebo: Bacteriostatic 0.9% Sodium Chloride
Overall Study Physician Decision	1	0
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

Intranasal Glulisine in Amnestic Mild Cognitive Impairment and Probable Mild Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Insulin Glulisine n=19 Participants Insulin Glulisine 20 IU (0.1ml/10 units in each nostril) per intranasal dose, 2 times per day for 6 months Insulin glulisine	Placebo n=16 Participants Saline 20 IU (0.1 ml in each nostril) per intranasal dose, 2 times per day for 6 months Placebo: Bacteriostatic 0.9% Sodium Chloride	Total n=35 Participants Total of all reporting groups
Age, Continuous	68.4 years STANDARD_DEVIATION 8.1 • n=5 Participants	74.4 years STANDARD_DEVIATION 6.4 • n=7 Participants	71.1 years STANDARD_DEVIATION 7.9 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants	16 Participants n=7 Participants	35 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 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
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	12 Participants n=7 Participants	30 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants	16 participants n=7 Participants	35 participants n=5 Participants
Non-insulin dependent diabetes	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Montreal cognitive assessment (MoCA)	20.7 score on a scale STANDARD_DEVIATION 2.1 • n=5 Participants	21.1 score on a scale STANDARD_DEVIATION 2.5 • n=7 Participants	20.9 score on a scale STANDARD_DEVIATION 2.3 • n=5 Participants
Diagnosis of probable mild Alzheimer's disease (AD) or amnestic mild cognitive impairment (aMCI) Probable Mild AD	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Diagnosis of probable mild Alzheimer's disease (AD) or amnestic mild cognitive impairment (aMCI) aMCI	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants
Apolipoprotein E4 (APOEe) status Positive	14 Participants n=5 Participants	10 Participants n=7 Participants	24 Participants n=5 Participants
Apolipoprotein E4 (APOEe) status Negative	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 6 months

Outcome measures

Outcome measures
Measure	Insulin Glulisine n=16 Participants Insulin Glulisine 20 IU (0.1ml/10 units in each nostril) per intranasal dose, 2 times per day for 6 months Insulin glulisine	Placebo n=12 Participants Saline 20 IU (0.1 ml in each nostril) per intranasal dose, 2 times per day for 6 months Placebo: Bacteriostatic 0.9% Sodium Chloride
Change in Cognition as Measured by the Alzheimer's Disease Assessment Scale - Cognitive 13 (ADAS-Cog 13)	1.56 score on a scale Standard Deviation 4.2	0.81 score on a scale Standard Deviation 4.8

PRIMARY outcome

Timeframe: Baseline and 6 months

The CDR is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to Alzheimer disease and related dementias: Memory, Orientation, Judgment \& Problem Solving, Community Affairs, Home \& Hobbies, and Personal Care. Possible scores on the CDR are 0 (no impairment), 0.5 (very mild), 1 (mild), 2 (moderate), and 3 (severe). The total CDR ratings for each of the six cognitive/functional domains can be added to create a CDR sum of boxes (SOB). The overall SOB score ranges from 0 to 18; with 18 indicating severe impairment and 0 indicating no impairment.

Outcome measures

Outcome measures
Measure	Insulin Glulisine n=16 Participants Insulin Glulisine 20 IU (0.1ml/10 units in each nostril) per intranasal dose, 2 times per day for 6 months Insulin glulisine	Placebo n=12 Participants Saline 20 IU (0.1 ml in each nostril) per intranasal dose, 2 times per day for 6 months Placebo: Bacteriostatic 0.9% Sodium Chloride
Change in Functional Performance as Measured by the Clinical Dementia Rating (CDR) Scale	0.53 score on a scale Standard Deviation .9	-0.08 score on a scale Standard Deviation 1.5

PRIMARY outcome

Timeframe: Baseline and 6 months

The FAQ measures instrumental activities of daily living (IADLs), such as preparing balanced meals and managing personal finances. The FAQ is a sum of scores ranging from 0 (normal) to 30 (complete dependence on others).

Outcome measures

Outcome measures
Measure	Insulin Glulisine n=16 Participants Insulin Glulisine 20 IU (0.1ml/10 units in each nostril) per intranasal dose, 2 times per day for 6 months Insulin glulisine	Placebo n=12 Participants Saline 20 IU (0.1 ml in each nostril) per intranasal dose, 2 times per day for 6 months Placebo: Bacteriostatic 0.9% Sodium Chloride
Change in Functional Performance as Measured by the Functional Activities Questionnaire (FAQ)	2.5 score on a scale Standard Deviation 3.2	0.92 score on a scale Standard Deviation 3.4

Adverse Events

Insulin Glulisine

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Insulin Glulisine n=19 participants at risk；n=16 participants at risk Insulin Glulisine 20 IU (0.1ml/10 units in each nostril) per intranasal dose, 2 times per day for 6 months Insulin glulisine	Placebo n=16 participants at risk；n=12 participants at risk Saline 20 IU (0.1 ml in each nostril) per intranasal dose, 2 times per day for 6 months Placebo: Bacteriostatic 0.9% Sodium Chloride
Renal and urinary disorders Hospitalization	6.2% 1/16 • Number of events 1 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.	0.00% 0/12 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.

Other adverse events

Additional Information

Clinical Research Manager

HealthPartners Neuroscience Research

Phone: 651-495-6363

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Insulin Glulisine n=19 participants at risk；n=16 participants at risk Insulin Glulisine 20 IU (0.1ml/10 units in each nostril) per intranasal dose, 2 times per day for 6 months Insulin glulisine	Placebo n=16 participants at risk；n=12 participants at risk Saline 20 IU (0.1 ml in each nostril) per intranasal dose, 2 times per day for 6 months Placebo: Bacteriostatic 0.9% Sodium Chloride
Skin and subcutaneous tissue disorders Nasal Irritation	57.9% 11/19 • Number of events 11 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.	31.2% 5/16 • Number of events 5 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.
Respiratory, thoracic and mediastinal disorders Respiratory/Sinus symptoms	31.6% 6/19 • Number of events 7 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.	18.8% 3/16 • Number of events 3 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.
Musculoskeletal and connective tissue disorders Musculoskeletal	15.8% 3/19 • Number of events 4 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.	31.2% 5/16 • Number of events 8 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.
General disorders Imbalance/falls	21.1% 4/19 • Number of events 4 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.	18.8% 3/16 • Number of events 5 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.
General disorders Injury related to falls	0.00% 0/19 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.	18.8% 3/16 • Number of events 7 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.
Surgical and medical procedures Dental	10.5% 2/19 • Number of events 3 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.	6.2% 1/16 • Number of events 1 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.
Cardiac disorders Cardiovascular	10.5% 2/19 • Number of events 2 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.	12.5% 2/16 • Number of events 2 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.
Gastrointestinal disorders Gastrointestinal	10.5% 2/19 • Number of events 4 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.	12.5% 2/16 • Number of events 2 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.
Infections and infestations Infection	10.5% 2/19 • Number of events 2 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.	0.00% 0/16 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.
General disorders Nausea	5.3% 1/19 • Number of events 1 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.	6.2% 1/16 • Number of events 1 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.
Skin and subcutaneous tissue disorders Cancer	5.3% 1/19 • Number of events 1 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.	6.2% 1/16 • Number of events 1 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.
Eye disorders Opthalmic	5.3% 1/19 • Number of events 1 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.	6.2% 1/16 • Number of events 1 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.
General disorders Hypoglycemia	5.3% 1/19 • Number of events 1 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.	0.00% 0/16 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.
Blood and lymphatic system disorders Hematologic	5.3% 1/19 • Number of events 1 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.	0.00% 0/16 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.
Ear and labyrinth disorders Hearing Loss	5.3% 1/19 • Number of events 1 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.	0.00% 0/16 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.
Endocrine disorders Endocrine	5.3% 1/19 • Number of events 1 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.	0.00% 0/16 • 8 months Adverse event information was collected only from participants who were randomized to one of the two treatment groups. Participants who screen failed, withdrew, or were withdrawn prior to randomization are not included.