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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Parkinson Disease, Multiple System Atrophy

Intervention / Treatment
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* Drug: Intranasal Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females older than 17 years. Clinical diagnosis of Parkinson disease or multiple system atrophy. Provide written informed consent to participate in the study. Understand that they may withdraw their consent at any time. Exclusion Criteria: Women who are pregnant or lactating. In the investigator's opinion, have significant systemic, hepatic, cardiovascular, renal or other illness that can interfere based on investigator judgment with the trial. History of dementia. Unable to walk without help for at least 1 minute. History of allergic reaction to insulin. The presence of inflammation of nasal cavity that may prevents absorption of insulin.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin<br>40 IU of intranasal insulin daily | Drug: Intranasal Insulin<br>* treatment arm: Insulin, 40 international units daily, intranasally, for 4 weeks; placebo arm: normal saline, daily, intranasally, for 4 weeks.<br>* Other names: Novolin R;|
| Placebo Comparator: Placebo<br>Placebo arm using intranasal normal saline | Drug: Intranasal Insulin<br>* treatment arm: Insulin, 40 international units daily, intranasally, for 4 weeks; placebo arm: normal saline, daily, intranasally, for 4 weeks.<br>* Other names: Novolin R;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Hoehn and Yahr Scale | 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. | Baseline and post-treatment | 
| Cognitive Impairment Using Montreal Cognitive Assessment (MoCA) | 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. | Baseline and post-treatment | 
| Beck Depression Inventory Score (BDI) | 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. | Baseline and post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson disease, Multiple system atrophy, Intranasal, Insulin