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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02503501
Recruitment Status : Terminated (Study will not have power to show a difference between groups.)
First Posted : July 21, 2015
Results First Posted : April 9, 2020
Last Update Posted : April 9, 2020
Sponsor:
Information provided by (Responsible Party):
HealthPartners Institute

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Mild Cognitive Impairment
Alzheimer's Disease (AD)
Interventions Drug: Insulin glulisine
Drug: Placebo
Enrollment 49
Recruitment Details  
Pre-assignment Details 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.
Arm/Group Title Insulin Glulisine Placebo
Hide Arm/Group Description

Insulin Glulisine 20 IU (0.1ml/10 units in each nostril) per intranasal dose, 2 times per day for 6 months

Insulin glulisine

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

Period Title: Overall Study
Started 19 16
Completed 18 13
Not Completed 1 3
Reason Not Completed
Physician Decision             1             0
Protocol Violation             0             1
Withdrawal by Subject             0             2
Arm/Group Title Insulin Glulisine Placebo Total
Hide Arm/Group Description

Insulin Glulisine 20 IU (0.1ml/10 units in each nostril) per intranasal dose, 2 times per day for 6 months

Insulin glulisine

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 of all reporting groups
Overall Number of Baseline Participants 19 16 35
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 16 participants 35 participants
68.4  (8.1) 74.4  (6.4) 71.1  (7.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 16 participants 35 participants
Female
9
  47.4%
6
  37.5%
15
  42.9%
Male
10
  52.6%
10
  62.5%
20
  57.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 16 participants 35 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
19
 100.0%
16
 100.0%
35
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 16 participants 35 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
2
  12.5%
2
   5.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   5.3%
0
   0.0%
1
   2.9%
White
18
  94.7%
12
  75.0%
30
  85.7%
More than one race
0
   0.0%
1
   6.3%
1
   2.9%
Unknown or Not Reported
0
   0.0%
1
   6.3%
1
   2.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 19 participants 16 participants 35 participants
19 16 35
Non-insulin dependent diabetes  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 16 participants 35 participants
3
  15.8%
2
  12.5%
5
  14.3%
Montreal cognitive assessment (MoCA)   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 19 participants 16 participants 35 participants
20.7  (2.1) 21.1  (2.5) 20.9  (2.3)
[1]
Measure Description: The Montreal Cognitive Assessment (MoCA) was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. The time to administer the MoCA is approximately 10 minutes. The scale ranges from 0-30 points, and scores of 26 or above are considered normal.
Diagnosis of probable mild Alzheimer's disease (AD) or amnestic mild cognitive impairment (aMCI)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 16 participants 35 participants
Probable Mild AD
10
  52.6%
11
  68.8%
21
  60.0%
aMCI
9
  47.4%
5
  31.3%
14
  40.0%
[1]
Measure Description: Diagnosis of AD or aMCI by a neurologist. aMCI is characterized by memory complaints and neuropsychological testing demonstrating abnormalities >1.0 standard deviation affecting memory with preservation of instrumental activities of daily living without functional limitations. The population has a 40% change of developing AD within 2 years. AD is chronic progressive neurodegenerative condition resulting in memory impairment, loss of function, and progressive deterioration in other cognitive domains like language, perceptual skills, attention, construction, orientation, and problem solving
Apolipoprotein E4 (APOEe) status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 16 participants 35 participants
Positive
14
  73.7%
10
  62.5%
24
  68.6%
Negative
5
  26.3%
6
  37.5%
11
  31.4%
1.Primary Outcome
Title Change in Cognition as Measured by the Alzheimer's Disease Assessment Scale - Cognitive 13 (ADAS-Cog 13)
Hide Description 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).
Time Frame Baseline and 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Insulin Glulisine Placebo
Hide Arm/Group Description:

Insulin Glulisine 20 IU (0.1ml/10 units in each nostril) per intranasal dose, 2 times per day for 6 months

Insulin glulisine

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 Number of Participants Analyzed 16 12
Mean (Standard Deviation)
Unit of Measure: score on a scale
1.56  (4.2) 0.81  (4.8)
2.Primary Outcome
Title Change in Functional Performance as Measured by the Clinical Dementia Rating (CDR) Scale
Hide Description 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.
Time Frame Baseline and 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Insulin Glulisine Placebo
Hide Arm/Group Description:

Insulin Glulisine 20 IU (0.1ml/10 units in each nostril) per intranasal dose, 2 times per day for 6 months

Insulin glulisine

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 Number of Participants Analyzed 16 12
Mean (Standard Deviation)
Unit of Measure: score on a scale
0.53  (.9) -0.08  (1.5)
3.Primary Outcome
Title Change in Functional Performance as Measured by the Functional Activities Questionnaire (FAQ)
Hide Description 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).
Time Frame Baseline and 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Insulin Glulisine Placebo
Hide Arm/Group Description:

Insulin Glulisine 20 IU (0.1ml/10 units in each nostril) per intranasal dose, 2 times per day for 6 months

Insulin glulisine

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 Number of Participants Analyzed 16 12
Mean (Standard Deviation)
Unit of Measure: score on a scale
2.5  (3.2) 0.92  (3.4)
Time Frame 8 months
Adverse Event Reporting Description 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.
 
Arm/Group Title Insulin Glulisine Placebo
Hide Arm/Group Description

Insulin Glulisine 20 IU (0.1ml/10 units in each nostril) per intranasal dose, 2 times per day for 6 months

Insulin glulisine

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

All-Cause Mortality
Insulin Glulisine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)      0/12 (0.00%)    
Hide Serious Adverse Events
Insulin Glulisine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/16 (6.25%)      0/12 (0.00%)    
Renal and urinary disorders     
Hospitalization * [1]  1/16 (6.25%)  1 0/12 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
[1]
Dizziness secondary to dehydration and hyponatremia secondary to vomiting + hydrochlorothiazide
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Insulin Glulisine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   17/19 (89.47%)      10/16 (62.50%)    
Blood and lymphatic system disorders     
Hematologic *  1/19 (5.26%)  1 0/16 (0.00%)  0
Cardiac disorders     
Cardiovascular *  2/19 (10.53%)  2 2/16 (12.50%)  2
Ear and labyrinth disorders     
Hearing Loss *  1/19 (5.26%)  1 0/16 (0.00%)  0
Endocrine disorders     
Endocrine *  1/19 (5.26%)  1 0/16 (0.00%)  0
Eye disorders     
Opthalmic *  1/19 (5.26%)  1 1/16 (6.25%)  1
Gastrointestinal disorders     
Gastrointestinal *  2/19 (10.53%)  4 2/16 (12.50%)  2
General disorders     
Imbalance/falls *  4/19 (21.05%)  4 3/16 (18.75%)  5
Injury related to falls *  0/19 (0.00%)  0 3/16 (18.75%)  7
Nausea *  1/19 (5.26%)  1 1/16 (6.25%)  1
Hypoglycemia *  1/19 (5.26%)  1 0/16 (0.00%)  0
Infections and infestations     
Infection *  2/19 (10.53%)  2 0/16 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Musculoskeletal *  3/19 (15.79%)  4 5/16 (31.25%)  8
Respiratory, thoracic and mediastinal disorders     
Respiratory/Sinus symptoms *  6/19 (31.58%)  7 3/16 (18.75%)  3
Skin and subcutaneous tissue disorders     
Nasal Irritation *  11/19 (57.89%)  11 5/16 (31.25%)  5
Cancer *  1/19 (5.26%)  1 1/16 (6.25%)  1
Surgical and medical procedures     
Dental *  2/19 (10.53%)  3 1/16 (6.25%)  1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Research Manager
Organization: HealthPartners Neuroscience Research
Phone: 651-495-6363
EMail: aleta.l.svitak@healthpartners.com
Layout table for additonal information
Responsible Party: HealthPartners Institute
ClinicalTrials.gov Identifier: NCT02503501    
Other Study ID Numbers: IN-INSUL-MCI-AD
First Submitted: July 14, 2015
First Posted: July 21, 2015
Results First Submitted: March 6, 2020
Results First Posted: April 9, 2020
Last Update Posted: April 9, 2020