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

A Double-blinded Placebo-controlled Single-center Study to Evaluate the Efficacy of Intranasal Insulin 40 International Units Day as Treatment for Subjects With Parkinson Disease and Multiple System Atrophy

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02064166

Enrollment

Registered

2014-02-17

Start date

2014-02-28

Completion date

2015-09-30

Last updated

2018-11-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Multiple System Atrophy, Parkinson Disease

Keywords

Parkinson disease, Multiple system atrophy, Intranasal, Insulin

Brief summary

Parkinson disease (PD) and multiple system atrophy (MSA) are progressive neurodegenerative disorders characterized by abnormal accumulation of α-synuclein. There is no effective treatment that can slow down the disease progression and both disorders are associated with severe cognitive decline. It was shown that intranasal insulin (INI) improves learning and memory in healthy and cognitively impaired non-diabetic adults. The proof-of-concept, randomized, placebo-controlled, cross-over pilot study ( NCT01206322) has shown that a single 40 international units dose of intranasal insulin improves visuospatial memory in diabetes and control subjects. This proposal includes randomized, double blinded, placebo-controlled trial of intranasal insulin (40 international units daily) in treatment of PD and MSA. The study will evaluate 22 patients with PD and 22 patients with MSA. Total duration of the study will be 2 years. The primary goal is to assess the efficacy of INI in treatment of cognitive abnormalities in both PD and MSA. The primary efficacy end point will be change of the cognitive scale ratings.

Interventions

DRUGIntranasal Insulin

1. treatment arm: Insulin, 40 international units daily, intranasally, for 4 weeks; 2. placebo arm: normal saline, daily, intranasally, for 4 weeks.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Males or females older than 17 years. 2. Clinical diagnosis of Parkinson disease or multiple system atrophy. 3. Provide written informed consent to participate in the study. 4. Understand that they may withdraw their consent at any time.

Exclusion criteria

1. Women who are pregnant or lactating. 2. In the investigator's opinion, have significant systemic, hepatic, cardiovascular, renal or other illness that can interfere based on investigator judgment with the trial. 3. History of dementia. 4. Unable to walk without help for at least 1 minute. 5. History of allergic reaction to insulin. 6. The presence of inflammation of nasal cavity that may prevents absorption of insulin.

Design outcomes

Primary

Measure	Time frame	Description
Change in Verbal Fluency FAS (F, A or S Words) Total Score	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.

Secondary

Measure	Time frame	Description
Modified Hoehn and Yahr Scale	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.
Cognitive Impairment Using Montreal Cognitive Assessment (MoCA)	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.
Beck Depression Inventory Score (BDI)	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.

Other

Measure	Time frame	Description
Gait Analysis (4-meter Test)	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.
Brief Visuospatial Memory Test-Revised (BVMT-R)	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.
Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III)	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Insulin 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.	8
Placebo 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.	6
Total	14

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	0

Baseline characteristics

Characteristic	Placebo	Insulin	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	3 Participants	3 Participants	6 Participants
Age, Categorical Between 18 and 65 years	3 Participants	5 Participants	8 Participants
Age, Continuous	62.2 years STANDARD_DEVIATION 9.6	63.4 years STANDARD_DEVIATION 5.7	62.9 years STANDARD_DEVIATION 7.2
Region of Enrollment United States	6 Participants	8 Participants	14 Participants
Sex: Female, Male Female	3 Participants	3 Participants	6 Participants
Sex: Female, Male Male	3 Participants	5 Participants	8 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 9	0 / 6
other Total, other adverse events	1 / 9	0 / 6
serious Total, serious adverse events	0 / 9	0 / 6

Outcome results

Primary

Change in Verbal Fluency FAS (F, A or S Words) Total Score

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.