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

Phase 2

Completed

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.

Recruitment & Eligibility

Inclusion Criteria

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.

Arm && Interventions

Group	Intervention	Description
Placebo	Intranasal Insulin	Placebo arm using intranasal normal saline
Insulin	Intranasal Insulin	40 IU of intranasal insulin daily

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.