Trial Outcomes & Findings for Treatment of Parkinson Disease and Multiple System Atrophy Using Intranasal Insulin. (NCT NCT02064166)

NCT ID: NCT02064166

Last Updated: 2018-11-23

Results Overview

Changes in Verbal Fluency FAS (a total number of F, A or S words) generated after 4 weeks of treatment compared to baseline, FAS total score is a sum of F,A, and S raw scores. The verbal fluency FAS test is used to assess phonemic fluency and verbal memory. Participants are asked to name words starting with letters F, A and S over one minute interval. The unit is a on scale, the normative data are adjusted for age and sex. The higher score means better verbal fluency.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

15 participants

Primary outcome timeframe

Baseline and post-treatment

Results posted on

2018-11-23

Participant Flow

Participant milestones

Participant milestones
Measure
Insulin
Treatment arm: 40 IU of intranasal human insulin Novolin R, Novo Nordisk daily Intranasal Insulin: Insulin, 40 IU of daily, intranasally, for 4 weeks;
Placebo
Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks.
Overall Study
STARTED
9
6
Overall Study
COMPLETED
8
6
Overall Study
NOT COMPLETED
1
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Insulin
Treatment arm: 40 IU of intranasal human insulin Novolin R, Novo Nordisk daily Intranasal Insulin: Insulin, 40 IU of daily, intranasally, for 4 weeks;
Placebo
Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks.
Overall Study
Adverse Event
1
0

Baseline Characteristics

Treatment of Parkinson Disease and Multiple System Atrophy Using Intranasal Insulin.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Insulin
n=8 Participants
40 IU of intranasal insulin daily Intranasal Insulin: 1.treatment arm: Insulin, 40 international units daily, intranasally, for 4 weeks; 2. placebo arm: normal saline, daily, intranasally, for 4 weeks.
Placebo
n=6 Participants
Placebo arm using intranasal normal saline Intranasal Insulin: 1.treatment arm: Insulin, 40 international units daily, intranasally, for 4 weeks; 2. placebo arm: normal saline, daily, intranasally, for 4 weeks.
Total
n=14 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
Age, Categorical
Between 18 and 65 years
5 Participants
n=5 Participants
3 Participants
n=7 Participants
8 Participants
n=5 Participants
Age, Categorical
>=65 years
3 Participants
n=5 Participants
3 Participants
n=7 Participants
6 Participants
n=5 Participants
Age, Continuous
63.4 years
STANDARD_DEVIATION 5.7 • n=5 Participants
62.2 years
STANDARD_DEVIATION 9.6 • n=7 Participants
62.9 years
STANDARD_DEVIATION 7.2 • n=5 Participants
Sex: Female, Male
Female
3 Participants
n=5 Participants
3 Participants
n=7 Participants
6 Participants
n=5 Participants
Sex: Female, Male
Male
5 Participants
n=5 Participants
3 Participants
n=7 Participants
8 Participants
n=5 Participants
Region of Enrollment
United States
8 Participants
n=5 Participants
6 Participants
n=7 Participants
14 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline and post-treatment

Changes in Verbal Fluency FAS (a total number of F, A or S words) generated after 4 weeks of treatment compared to baseline, FAS total score is a sum of F,A, and S raw scores. The verbal fluency FAS test is used to assess phonemic fluency and verbal memory. Participants are asked to name words starting with letters F, A and S over one minute interval. The unit is a on scale, the normative data are adjusted for age and sex. The higher score means better verbal fluency.

Outcome measures

Outcome measures
Measure
Insulin Baseline
n=8 Participants
FAS score in the insulin group at baseline Treatment arm: 40 IU of intranasal human insulin Novolin R, Novo Nordisk daily Intranasal Insulin: Insulin, 40 IU of daily, intranasally, for 4 weeks;
Insulin Post Treatment
n=8 Participants
FAS score in the insulin group post treatment Treatment arm: 40 IU of intranasal human insulin Novolin R, Novo Nordisk daily Intranasal Insulin: Insulin, 40 IU of daily, intranasally, for 4 weeks;
Placebo Baseline
n=6 Participants
FAS score in the placebo group at baseline Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks.
Placebo Post Treatment
n=6 Participants
FAS score in the placebo group post treatment Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks
Change in Verbal Fluency FAS (F, A or S Words) Total Score
38.8 Words
Standard Deviation 5.7
41.0 Words
Standard Deviation 8.2
32.8 Words
Standard Deviation 2.3
30.8 Words
Standard Deviation 7.1

SECONDARY outcome

Timeframe: Baseline and post-treatment

The modified Hoehn and Yahr Scale (HY) is used to assess severity of Parkinson Disease and treatment response post treatment as compared to baseline. The scale ranges from 1 to 5. The lower score indicates better outcome, e.g. less severe parkinsonism.

Outcome measures

Outcome measures
Measure
Insulin Baseline
n=8 Participants
FAS score in the insulin group at baseline Treatment arm: 40 IU of intranasal human insulin Novolin R, Novo Nordisk daily Intranasal Insulin: Insulin, 40 IU of daily, intranasally, for 4 weeks;
Insulin Post Treatment
n=8 Participants
FAS score in the insulin group post treatment Treatment arm: 40 IU of intranasal human insulin Novolin R, Novo Nordisk daily Intranasal Insulin: Insulin, 40 IU of daily, intranasally, for 4 weeks;
Placebo Baseline
n=6 Participants
FAS score in the placebo group at baseline Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks.
Placebo Post Treatment
n=6 Participants
FAS score in the placebo group post treatment Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks
Modified Hoehn and Yahr Scale
2.0 score on a scale
Standard Deviation 0.6
2.0 score on a scale
Standard Deviation 0.7
2.4 score on a scale
Standard Deviation 0.38
2.4 score on a scale
Standard Deviation 0.2

SECONDARY outcome

Timeframe: Baseline and post-treatment

The Montreal Cognitive Assessment (MoCA) is a one-page 30-point test administered in approximately 10 minutes and is used to assess symptoms of cognitive impairment and their changes after treatment as compared to baseline. MoCA scores range between 0 and 30 with higher scores indicative of better cognitive performance. A score of 26 and above is considered to be normal.

Outcome measures

Outcome measures
Measure
Insulin Baseline
n=8 Participants
FAS score in the insulin group at baseline Treatment arm: 40 IU of intranasal human insulin Novolin R, Novo Nordisk daily Intranasal Insulin: Insulin, 40 IU of daily, intranasally, for 4 weeks;
Insulin Post Treatment
n=8 Participants
FAS score in the insulin group post treatment Treatment arm: 40 IU of intranasal human insulin Novolin R, Novo Nordisk daily Intranasal Insulin: Insulin, 40 IU of daily, intranasally, for 4 weeks;
Placebo Baseline
n=6 Participants
FAS score in the placebo group at baseline Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks.
Placebo Post Treatment
n=6 Participants
FAS score in the placebo group post treatment Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks
Cognitive Impairment Using Montreal Cognitive Assessment (MoCA)
28.7 score on a scale
Standard Deviation 1.2
28.0 score on a scale
Standard Deviation 1.1
26.8 score on a scale
Standard Deviation 2.6
28.2 score on a scale
Standard Deviation 0.95

SECONDARY outcome

Timeframe: Baseline and post-treatment

Beck Depression Inventory (BDI) is a 21-items self reported inventory with a scale evaluating depressive symptoms and the changes in BDI after treatment compared to baseline. The range of scores is 0 to 63, with higher scores indicating greater severity of depression.

Outcome measures

Outcome measures
Measure
Insulin Baseline
n=8 Participants
FAS score in the insulin group at baseline Treatment arm: 40 IU of intranasal human insulin Novolin R, Novo Nordisk daily Intranasal Insulin: Insulin, 40 IU of daily, intranasally, for 4 weeks;
Insulin Post Treatment
n=8 Participants
FAS score in the insulin group post treatment Treatment arm: 40 IU of intranasal human insulin Novolin R, Novo Nordisk daily Intranasal Insulin: Insulin, 40 IU of daily, intranasally, for 4 weeks;
Placebo Baseline
n=6 Participants
FAS score in the placebo group at baseline Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks.
Placebo Post Treatment
n=6 Participants
FAS score in the placebo group post treatment Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks
Beck Depression Inventory Score (BDI)
7.8 score on a scale
Standard Deviation 5.4
8.25 score on a scale
Standard Deviation 8.1
13.5 score on a scale
Standard Deviation 5.6
12.8 score on a scale
Standard Deviation 7.4

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and post-treatment

UPDRS Part III has 14 items assessing motor skills including facial expression and speech, tremors, rigidity, posture, gait, and bradykinesia. Left and right sides (arms, legs, and hands) are assessed separately for seven of the functions. The total score for subscale 3 ranges from 0 to 108 (the sum of scores from 14 items with 27 observations). The higher the value, the more severe the symptoms. The outcomes reflect the UPDRS Part III score at baseline and 4 weeks post treatment with post treatment scores compared to baseline in the insulin and placebo groups.

Outcome measures

Outcome measures
Measure
Insulin Baseline
n=8 Participants
FAS score in the insulin group at baseline Treatment arm: 40 IU of intranasal human insulin Novolin R, Novo Nordisk daily Intranasal Insulin: Insulin, 40 IU of daily, intranasally, for 4 weeks;
Insulin Post Treatment
n=8 Participants
FAS score in the insulin group post treatment Treatment arm: 40 IU of intranasal human insulin Novolin R, Novo Nordisk daily Intranasal Insulin: Insulin, 40 IU of daily, intranasally, for 4 weeks;
Placebo Baseline
n=6 Participants
FAS score in the placebo group at baseline Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks.
Placebo Post Treatment
n=6 Participants
FAS score in the placebo group post treatment Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks
Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III)
31.5 score on a scale
Standard Deviation 20.0
25.6 score on a scale
Standard Deviation 21.8
31.7 score on a scale
Standard Deviation 13.3
30.5 score on a scale
Standard Deviation 15.8

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and post-treatment

Changes in gait compared to baseline. Data are reported as changes in average stride interval ( inch) at baseline and post treatment.

Outcome measures

Outcome measures
Measure
Insulin Baseline
n=8 Participants
FAS score in the insulin group at baseline Treatment arm: 40 IU of intranasal human insulin Novolin R, Novo Nordisk daily Intranasal Insulin: Insulin, 40 IU of daily, intranasally, for 4 weeks;
Insulin Post Treatment
n=8 Participants
FAS score in the insulin group post treatment Treatment arm: 40 IU of intranasal human insulin Novolin R, Novo Nordisk daily Intranasal Insulin: Insulin, 40 IU of daily, intranasally, for 4 weeks;
Placebo Baseline
n=6 Participants
FAS score in the placebo group at baseline Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks.
Placebo Post Treatment
n=6 Participants
FAS score in the placebo group post treatment Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks
Gait Analysis (4-meter Test)
22.0 inch
Standard Deviation 5.0
21.5 inch
Standard Deviation 4.4
21.0 inch
Standard Deviation 2.7
19.6 inch
Standard Deviation 2.9

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and post-treatment

Changes in Brief Visuospatial Memory Test-Revised (BMVT-R) compared to baseline. For BVMT, there were concerns about the test administration and validity of this test which relies on fine motor control in PD patients that have motor impairment which could affect the drawing precision. Therefore, BVMT was not included in the analyses, because these methodological concerns would have affected the calculation of the total score as the outcome measure.

Outcome measures

Outcome data not reported

Adverse Events

Insulin

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Placebo

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
Insulin
n=9 participants at risk
40 IU of intranasal insulin daily Intranasal Insulin: 1.treatment arm: Insulin, 40 international units daily, intranasally, for 4 weeks; 2. placebo arm: normal saline, daily, intranasally, for 4 weeks.
Placebo
n=6 participants at risk
Placebo arm using intranasal normal saline Intranasal Insulin: 1.treatment arm: Insulin, 40 international units daily, intranasally, for 4 weeks; 2. placebo arm: normal saline, daily, intranasally, for 4 weeks.
Respiratory, thoracic and mediastinal disorders
Pneumonia
11.1%
1/9 • Number of events 1
0.00%
0/6

Additional Information

Peter Novak, MD PhD

Brigham & Women's Hospital

Phone: 617-732-8896

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place