Trial Outcomes & Findings for Intranasal Insulin in Parkinson's Disease (NCT NCT04251585)
NCT ID: NCT04251585
Last Updated: 2026-02-11
Results Overview
Composite safety event - this is a count of either a reduction of fasting glucose to \<70 mg/dL or an unintended reduction of weight \>5%. A larger composite event count indicates a less safe treatment.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
31 participants
Primary outcome timeframe
3 weeks
Results posted on
2026-02-11
Participant Flow
One participant was deemed ineligible prior to randomization. One participant completed treatment but was removed before analysis following the revision of eligibility criteria around MOCA score. 28 participants who completed treatment and were eligible were included in the analysis.
Participant milestones
| Measure |
Low Insulin
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
7
|
10
|
6
|
|
Overall Study
COMPLETED
|
6
|
7
|
9
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Intranasal Insulin in Parkinson's Disease
Baseline characteristics by cohort
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
Total
n=28 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
68.3 years
STANDARD_DEVIATION 5.0 • n=41 Participants
|
63.4 years
STANDARD_DEVIATION 5.1 • n=1581 Participants
|
68.2 years
STANDARD_DEVIATION 4.9 • n=4626 Participants
|
69.2 years
STANDARD_DEVIATION 6.1 • n=72 Participants
|
67.3 years
STANDARD_DEVIATION 5.5 • n=11 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=41 Participants
|
4 Participants
n=1581 Participants
|
5 Participants
n=4626 Participants
|
4 Participants
n=72 Participants
|
16 Participants
n=11 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=41 Participants
|
3 Participants
n=1581 Participants
|
4 Participants
n=4626 Participants
|
2 Participants
n=72 Participants
|
12 Participants
n=11 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=41 Participants
|
1 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
0 Participants
n=72 Participants
|
1 Participants
n=11 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=41 Participants
|
6 Participants
n=1581 Participants
|
9 Participants
n=4626 Participants
|
6 Participants
n=72 Participants
|
27 Participants
n=11 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
0 Participants
n=72 Participants
|
0 Participants
n=11 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
0 Participants
n=72 Participants
|
0 Participants
n=11 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
0 Participants
n=72 Participants
|
0 Participants
n=11 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
0 Participants
n=72 Participants
|
0 Participants
n=11 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
0 Participants
n=72 Participants
|
0 Participants
n=11 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=41 Participants
|
7 Participants
n=1581 Participants
|
9 Participants
n=4626 Participants
|
6 Participants
n=72 Participants
|
28 Participants
n=11 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
0 Participants
n=72 Participants
|
0 Participants
n=11 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
0 Participants
n=4626 Participants
|
0 Participants
n=72 Participants
|
0 Participants
n=11 Participants
|
|
Montreal Cognitive Assessment (MoCA)
|
26.8 units on a scale
STANDARD_DEVIATION 1.8 • n=41 Participants
|
27.3 units on a scale
STANDARD_DEVIATION 2.7 • n=1581 Participants
|
24.6 units on a scale
STANDARD_DEVIATION 3.0 • n=4626 Participants
|
24.5 units on a scale
STANDARD_DEVIATION 1.9 • n=72 Participants
|
25.7 units on a scale
STANDARD_DEVIATION 2.7 • n=11 Participants
|
|
UPDRS
|
24.2 units on a scale
STANDARD_DEVIATION 13.8 • n=41 Participants
|
24.5 units on a scale
STANDARD_DEVIATION 11.1 • n=1581 Participants
|
24.4 units on a scale
STANDARD_DEVIATION 12.0 • n=4626 Participants
|
24.3 units on a scale
STANDARD_DEVIATION 8.2 • n=72 Participants
|
24.4 units on a scale
STANDARD_DEVIATION 10.8 • n=11 Participants
|
|
Baseline HbA1C
|
5.7 percent
STANDARD_DEVIATION .2 • n=41 Participants
|
5.5 percent
STANDARD_DEVIATION .2 • n=1581 Participants
|
5.6 percent
STANDARD_DEVIATION .5 • n=4626 Participants
|
5.6 percent
STANDARD_DEVIATION .2 • n=72 Participants
|
5.6 percent
STANDARD_DEVIATION .3 • n=11 Participants
|
PRIMARY outcome
Timeframe: 3 weeksComposite safety event - this is a count of either a reduction of fasting glucose to \<70 mg/dL or an unintended reduction of weight \>5%. A larger composite event count indicates a less safe treatment.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Safety Measured by Count of Safety Events
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: baseline and 3 weeksPre-post change in fasting glucose (mg/dL). A larger decrease in fasting glucose indicates a less safe treatment.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Safety Measured by Fasting Glucose
|
-3.8 mg/dL
Interval -6.9 to -1.0
|
-1.3 mg/dL
Interval -6.8 to 4.2
|
-5.9 mg/dL
Interval -10.0 to -1.8
|
-3.8 mg/dL
Interval -9.8 to 2.1
|
PRIMARY outcome
Timeframe: baseline and 3 weeksPre-post change in body weight (lbs). An unintended decrease in body weight indicates a less safe treatment.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Safety Measured by Body Weight
|
-0.63 pounds
Interval -1.8 to 0.5
|
0.34 pounds
Interval -1.6 to 2.3
|
-0.33 pounds
Interval -1.9 to 1.3
|
-0.55 pounds
Interval -3.0 to 1.9
|
PRIMARY outcome
Timeframe: 3 weeksTotal number of AEs/SAEs during the course of treatment. More AEs/SAEs indicates a less safe treatment.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Safety Measured by the Number of Serious Adverse Events (SAE) and Adverse Events (AE)
AE
|
2.8 number of events
Standard Deviation 1.2
|
5.0 number of events
Standard Deviation 2.8
|
2.0 number of events
Standard Deviation 3.8
|
3.0 number of events
Standard Deviation 0.89
|
|
Safety Measured by the Number of Serious Adverse Events (SAE) and Adverse Events (AE)
SAE
|
0 number of events
Standard Deviation 0
|
0 number of events
Standard Deviation 0
|
0 number of events
Standard Deviation 0
|
0 number of events
Standard Deviation 0
|
SECONDARY outcome
Timeframe: 5 weeksPre-post difference. Total sum of scores. Range: 0-30. Higher score indicates less memory loss
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Cognitive Function Measured by the Montreal Cognitive Assessment (MoCA)
|
-1.0 score on a scale
Interval -3.0 to 1.0
|
-0.71 score on a scale
Interval -2.5 to 1.1
|
0.67 score on a scale
Interval -0.93 to 2.3
|
0.5 score on a scale
Interval -1.5 to 2.5
|
SECONDARY outcome
Timeframe: 3 weeksPre-post difference. Scaled score. Range: 1-19. Forward and backward. Lower score indicates more impairment.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=3 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Cognitive Function Measured by the Weschler Adult Intelligence Scale - Fourth Edition (WAIS-IV) Digit Span
Forward Digit Span
|
1.5 score on a scale
Interval -0.33 to 3.3
|
1.0 score on a scale
Interval -0.69 to 2.7
|
0.2 score on a scale
Interval -1.3 to 1.7
|
1.0 score on a scale
Interval -0.83 to 2.8
|
|
Cognitive Function Measured by the Weschler Adult Intelligence Scale - Fourth Edition (WAIS-IV) Digit Span
Backward Digit Span
|
0.0 score on a scale
Interval -2.0 to 2.0
|
-0.43 score on a scale
Interval -2.3 to 1.5
|
0.0 score on a scale
Interval -1.7 to 1.7
|
2.3 score on a scale
Interval 0.29 to 4.4
|
SECONDARY outcome
Timeframe: baseline and 3 weeksPre-post difference. T-score. Mean: 50, Standard deviation: 10. A higher T-score indicates a better outcome/performance. Clinically, 1-1.5 standard deviations would be significant, 2 standard deviations would be considered abnormal/impaired.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Cognitive Function Measured by the Trailmaking Test Part A Time
|
4.5 T-score
Interval -3.3 to 12.3
|
5.3 T-score
Interval -1.9 to 12.5
|
4.7 T-score
Interval -1.6 to 11.1
|
5.8 T-score
Interval -1.9 to 13.6
|
SECONDARY outcome
Timeframe: baseline and 3 weeksPre-post difference. T-score. Mean: 50, Standard deviation: 10. A higher T-score indicates a better outcome/performance. Clinically, 1-1.5 standard deviations would be significant, 2 standard deviations would be considered abnormal/impaired.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Cognitive Function Measured by the Trailmaking Test Part B Time
|
3.5 T-score
Interval -3.0 to 10.0
|
5.6 T-score
Interval -0.43 to 11.6
|
2.1 T-score
Interval -3.2 to 7.4
|
-2.8 T-score
Interval -9.3 to 3.7
|
SECONDARY outcome
Timeframe: 3 weeksPre-post difference. Total number of errors. No range. More errors indicate more impairment.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Cognitive Function Measured by the Trailmaking Test Parts A & B Errors
|
0 number of errors
Interval -1.8 to 7.8
|
0 number of errors
Interval -0.53 to 0.53
|
-0.56 number of errors
Interval -1.5 to 0.4
|
0 number of errors
Interval -0.66 to 0.66
|
SECONDARY outcome
Timeframe: baseline and 3 weeksJudgement of Line Orientation is an assessment of visuospatial ability. A Z-score of 0 represents the population mean. Pre-post difference. A positive difference indicates an improvement.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Cognitive Function Measured by the Judgement of Line Orientation
|
0.06 Z-score
Interval -0.64 to 0.7
|
0.19 Z-score
Interval -0.38 to 0.77
|
-0.44 Z-score
Interval -0.94 to 0.07
|
0.21 Z-score
Interval -0.41 to 0.84
|
SECONDARY outcome
Timeframe: baseline and 3 weeksPre-post difference. Scaled score. Range: 1-19. Logical memory immediate and delayed. Lower score indicates more impairment.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Cognitive Function Measured by the Logical Memory Scaled Scores
Delayed Recall
|
1.7 scaled score
Interval -0.15 to 3.5
|
4.0 scaled score
Interval 2.3 to 5.7
|
2.4 scaled score
Interval 0.96 to 3.7
|
2.5 scaled score
Interval -0.69 to 4.3
|
|
Cognitive Function Measured by the Logical Memory Scaled Scores
Immediate Recall
|
2.7 scaled score
Interval 0.23 to 5.1
|
2.4 scaled score
Interval 0.17 to 4.7
|
1.3 scaled score
Interval -0.66 to 3.3
|
3.5 scaled score
Interval 1.1 to 5.9
|
SECONDARY outcome
Timeframe: baseline and 3 weeksPopulation: No differences.
Pre-post difference in median category from baseline to 3 weeks on the Logical memory, recognition subscale. Scoring of this and all outcomes were based on best practices conveyed by study neuropsychologist during study design, and scoring approaches were chosen completely a priori. The recognition outcome of the LM test is derived from a series of conversions, as follows. First, the raw "process" score is converted to cumulative percentage (0-100). Because the cumulative percentage distribution is known to be skewed, best practice is to report scores as the following ordinal categorizations of cumulative percentages: \<1, 3-9, 10-16, 17-25, 26-50, 51-75, and \>75. To analyze them using simple statistics, these ordinal categories are converted to integer values (1-7), and the change in median ordinal category is presented along with 95% confidence intervals, generated by the Wilcoxon signed rank test with continuity correction.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Cognitive Function Measured by the Logical Memory, Recognition
|
1 Ordinal category
Interval 0.0 to 5.0
|
0 Ordinal category
Interval 0.0 to 2.0
|
0 Ordinal category
Interval -1.0 to 2.0
|
1 Ordinal category
Interval -1.0 to 3.0
|
SECONDARY outcome
Timeframe: baseline and 3 weeksPre-post difference. T-score. Mean: 50, Standard deviation: 10. A higher T-score indicates a better outcome/performance. Clinically, 1-1.5 standard deviations would be significant, 2 standard deviations would be considered abnormal/impaired.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Cognitive Function Measured by the Hopkins Verbal Learning Test - Revised (HVLT)
HVLT Immediate Recall
|
3.0 T-score
Interval -5.0 to 11.0
|
1.6 T-score
Interval -5.8 to 9.0
|
-4.6 T-score
Interval -11.1 to 2.0
|
0.0 T-score
Interval -8.0 to 8.0
|
|
Cognitive Function Measured by the Hopkins Verbal Learning Test - Revised (HVLT)
HVLT Delayed Recall
|
-0.17 T-score
Interval -8.5 to 8.2
|
3.1 T-score
Interval -4.6 to 10.8
|
-5.2 T-score
Interval -12.0 to 1.6
|
0.50 T-score
Interval -7.8 to 8.8
|
|
Cognitive Function Measured by the Hopkins Verbal Learning Test - Revised (HVLT)
HVLT Recognition
|
2.2 T-score
Interval -7.7 to 12.0
|
-4.4 T-score
Interval -13.5 to 4.7
|
-7.2 T-score
Interval -15.3 to 0.81
|
1.3 T-score
Interval -8.5 to 11.2
|
SECONDARY outcome
Timeframe: 3 weeksPre-post difference. T-score. Mean: 50, Standard deviation: 10. A higher T-score indicates a better outcome/performance. Clinically, 1-1.5 standard deviations would be significant, 2 standard deviations would be considered abnormal/impaired.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Cognitive Function Measured by the Visuospatial Memory Test - Revised (BVMT)
BVMT Immediate Recall
|
5.5 T-scores
Interval -23.2 to 13.2
|
-8.6 T-scores
Interval -15.7 to -1.4
|
-3.0 T-scores
Interval -9.3 to 3.3
|
-11.8 T-scores
Interval -19.6 to -4.1
|
|
Cognitive Function Measured by the Visuospatial Memory Test - Revised (BVMT)
BVMT Delayed Recall
|
-2.8 T-scores
Interval -10.3 to 4.7
|
-1.7 T-scores
Interval -8.5 to 3.8
|
-2.3 T-scores
Interval -8.5 to 3.8
|
-9.7 T-scores
Interval -17.7 to -2.2
|
SECONDARY outcome
Timeframe: baseline and 3 weeksPre-post difference. T-score. Mean: 50, Standard deviation: 10. A higher T-score indicates a better outcome/performance. Clinically, 1-1.5 standard deviations would be significant, 2 standard deviations would be considered abnormal/impaired.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Cognitive Function Measured by the Stroop Color Word Test (CWT)
Word reading
|
-0.83 T-score
Interval -5.4 to 3.8
|
9.9 T-score
Interval 5.6 to 14.4
|
2.8 T-score
Interval -0.97 to 6.5
|
1.7 T-score
Interval -2.9 to 6.3
|
|
Cognitive Function Measured by the Stroop Color Word Test (CWT)
Color naming
|
-2.3 T-score
Interval -6.7 to 2.0
|
6.3 T-score
Interval 2.2 to 10.3
|
1.8 T-score
Interval -1.8 to 5.4
|
2.5 T-score
Interval -1.9 to 6.9
|
|
Cognitive Function Measured by the Stroop Color Word Test (CWT)
Color-word
|
1.0 T-score
Interval -2.8 to 4.8
|
2.3 T-score
Interval -1.3 to 5.8
|
-1.7 T-score
Interval -4.8 to 1.5
|
2.8 T-score
Interval -0.98 to 6.7
|
|
Cognitive Function Measured by the Stroop Color Word Test (CWT)
Interference
|
2.2 T-score
Interval -1.8 to 6.2
|
-2.9 T-score
Interval -6.6 to 0.85
|
-1.8 T-score
Interval -5.1 to 1.5
|
1.3 T-score
Interval -2.7 to 5.3
|
SECONDARY outcome
Timeframe: baseline and 3 weeksPre-post difference. T-score. Mean: 50, Standard deviation: 10. A higher T-score indicates a better outcome/performance. Clinically, 1-1.5 standard deviations would be significant, 2 standard deviations would be considered abnormal/impaired.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Cognitive Function Measured by Fluency
Letter fluency
|
4.7 T-score
Interval -1.3 to 10.6
|
5.0 T-score
Interval -0.53 to 10.5
|
2.9 T-score
Interval -2.0 to 7.8
|
1.3 T-score
Interval -4.6 to 7.3
|
|
Cognitive Function Measured by Fluency
Category fluency
|
6.7 T-score
Interval 0.12 to 13.2
|
4.7 T-score
Interval -1.4 to 10.8
|
-1.8 T-score
Interval -7.1 to 3.6
|
1.5 T-score
Interval -5.1 to 8.1
|
SECONDARY outcome
Timeframe: baseline and 3 weeksPre-post difference. Raw score. Range: 0-63. Higher score indicates more symptomatic.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Mood Measured by the Beck Depression Inventory - Second Edition
|
-2.5 score on a scale
Interval -5.5 to 0.49
|
-2.3 score on a scale
Interval -5.1 to 0.48
|
0.22 score on a scale
Interval -2.2 to 2.7
|
1.3 score on a scale
Interval -2.6 to 5.3
|
SECONDARY outcome
Timeframe: baseline and 3 weeksPre-post difference. Raw score. Range: 0-42. Higher score indicates more symptomatic.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Apathy Measured by the Apathy Scale
|
0.67 score on a scale
Interval -3.3 to 4.6
|
-0.86 score on a scale
Interval -4.5 to 2.8
|
1.7 score on a scale
Interval -1.6 to 4.9
|
1.3 score on a scale
Interval -2.6 to 5.3
|
SECONDARY outcome
Timeframe: baseline and 3 weeksPre-post difference. Raw score. Range:1 or 0. 1 score - more symptomatic, 0 score - no symptoms.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Mood Measured by the Columbia Suicide Severity Rating (C-SSRS)
|
0 score on a scale
Interval 0.0 to 0.0
|
0 score on a scale
Interval 0.0 to 0.0
|
0 score on a scale
Interval 0.0 to 0.0
|
0 score on a scale
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: baseline and 3 weeksPre-post difference. Raw score. Range: 0-72. Higher score indicates more symptomatic.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Motor Function as Measured by the United Parkinson's Disease Rating Scale (UPDRS-III)
|
-0.17 score on a scale
Interval -8.4 to 8.0
|
2.0 score on a scale
Interval -5.6 to 9.6
|
-3.7 score on a scale
Interval -10.4 to 3.0
|
-0.50 score on a scale
Interval -8.7 to 7.7
|
SECONDARY outcome
Timeframe: baseline and 3 weeksPre-post difference in median category from baseline to 3 weeks on the Brief Visual Spatial Memory Test - Revised recognition. Scoring of this and all outcomes were based on best practices conveyed by study neuropsychologist during study design, and scoring approaches were chosen completely a priori. The recognition outcome of the BVMT test is derived from a series of conversions, as follows. First, the raw score is converted to cumulative percentage (0-100). Because the cumulative percentage distribution is known to be skewed, best practice is to report scores as the following ordinal categorizations of cumulative percentages: \<2, 2-5, 6-10, 11-16, \>16. To analyze them using simple statistics, these ordinal categories are converted to integer values (1-5), and the change in median ordinal category is presented along with 95% confidence intervals, generated by the Wilcoxon signed rank test with continuity correction.
Outcome measures
| Measure |
Low Insulin
n=6 Participants
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 Participants
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 Participants
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 Participants
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
Cognitive Function Measured by Visuospatial Memory Test - Revised (BVMT Recognition)
|
0 Ordinal category
Interval -3.0 to 1.0
|
0 Ordinal category
Interval 0.0 to 0.0
|
0 Ordinal category
Interval -1.0 to 0.0
|
-0.5 Ordinal category
Interval -1.0 to 0.0
|
Adverse Events
Low Insulin
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Medium Insulin
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
High Insulin
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Low Insulin
n=6 participants at risk
Regular insulin (Novolin-R) 20 international units (10 units) in one nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
Medium Insulin
n=7 participants at risk
Regular insulin (Novolin-R) 40 international units (10 units) in each nostril twice daily for 21 days, 100 µl volume.
Regular Novolin R: Intranasal insulin
|
High Insulin
n=9 participants at risk
Regular insulin (Novolin-R) 80 international units (10 units) in each nostril twice daily for 21 days, 200 µl volume.
Regular Novolin R: Intranasal insulin
|
Placebo
n=6 participants at risk
0.9% sodium chloride in each nostril twice daily for 21 days, 100 µl volume.
Placebo: Intranasal placebo (0.9% saline)
|
|---|---|---|---|---|
|
General disorders
Light-headedness, dizzyness
|
0.00%
0/6 • 5 weeks
|
0.00%
0/7 • 5 weeks
|
11.1%
1/9 • Number of events 1 • 5 weeks
|
0.00%
0/6 • 5 weeks
|
|
Skin and subcutaneous tissue disorders
Nasal irritation
|
66.7%
4/6 • Number of events 4 • 5 weeks
|
85.7%
6/7 • Number of events 11 • 5 weeks
|
66.7%
6/9 • Number of events 8 • 5 weeks
|
50.0%
3/6 • Number of events 3 • 5 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle aches, pains, and sprains
|
16.7%
1/6 • Number of events 1 • 5 weeks
|
14.3%
1/7 • Number of events 1 • 5 weeks
|
0.00%
0/9 • 5 weeks
|
16.7%
1/6 • Number of events 1 • 5 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory/sinus symptoms
|
33.3%
2/6 • Number of events 3 • 5 weeks
|
0.00%
0/7 • 5 weeks
|
44.4%
4/9 • Number of events 5 • 5 weeks
|
16.7%
1/6 • Number of events 1 • 5 weeks
|
|
Ear and labyrinth disorders
Falls
|
16.7%
1/6 • Number of events 2 • 5 weeks
|
0.00%
0/7 • 5 weeks
|
0.00%
0/9 • 5 weeks
|
16.7%
1/6 • Number of events 1 • 5 weeks
|
|
Blood and lymphatic system disorders
Increased blood pressure
|
33.3%
2/6 • Number of events 2 • 5 weeks
|
14.3%
1/7 • Number of events 1 • 5 weeks
|
0.00%
0/9 • 5 weeks
|
0.00%
0/6 • 5 weeks
|
|
General disorders
Nose bleeds
|
50.0%
3/6 • Number of events 5 • 5 weeks
|
85.7%
6/7 • Number of events 9 • 5 weeks
|
66.7%
6/9 • Number of events 14 • 5 weeks
|
100.0%
6/6 • Number of events 8 • 5 weeks
|
|
General disorders
Other
|
0.00%
0/6 • 5 weeks
|
71.4%
5/7 • Number of events 10 • 5 weeks
|
55.6%
5/9 • Number of events 5 • 5 weeks
|
33.3%
2/6 • Number of events 3 • 5 weeks
|
|
General disorders
Headache
|
0.00%
0/6 • 5 weeks
|
28.6%
2/7 • Number of events 2 • 5 weeks
|
11.1%
1/9 • Number of events 1 • 5 weeks
|
0.00%
0/6 • 5 weeks
|
|
Gastrointestinal disorders
Gastrointestinal issues
|
0.00%
0/6 • 5 weeks
|
14.3%
1/7 • Number of events 1 • 5 weeks
|
22.2%
2/9 • Number of events 2 • 5 weeks
|
0.00%
0/6 • 5 weeks
|
Additional Information
Bhavani Kashyap, PhD, MBBS
HealthPartners Institute Neuroscience Research Center
Phone: 651-495-6363
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place