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

• Sponsor: Peter Novak (Other)
• Overall Status: Completed
• CT.gov ID: NCT02064166
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arms: 2
• Duration (Months): 19
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease; Multiple System Atrophy	Drug: Intranasal Insulin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insulin 40 IU of intranasal insulin daily	Drug: Intranasal Insulin; treatment arm: Insulin, 40 international units daily, intranasally, for 4 weeks; placebo arm: normal saline, daily, intranasally, for 4 weeks.; Other Names: Novolin R
Placebo Comparator: Placebo Placebo arm using intranasal normal saline	Drug: Intranasal Insulin; treatment arm: Insulin, 40 international units daily, intranasally, for 4 weeks; placebo arm: normal saline, daily, intranasally, for 4 weeks.; Other Names: Novolin R

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655

Sponsors and Collaborators

• Peter Novak

Investigators

• Principal Investigator: Peter Novak', MD,PhD, Former Associate Professor

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Peter Novak, Former Faculty member, University of Massachusetts, Worcester
• ClinicalTrials.gov Identifier: NCT02064166
• Other Study ID Numbers: PN-1
• First Posted: Feb 17, 2014
• Last Update Posted: Nov 23, 2018
• Last Verified: Nov 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Peter Novak, Former Faculty member, University of Massachusetts, Worcester: Parkinson disease; Multiple system atrophy; Intranasal; Insulin
• Additional relevant MeSH terms: Parkinson Disease; Multiple System Atrophy; Shy-Drager Syndrome; Atrophy; Insulin

Study Results

Participant Flow

Arm/Group Title	Insulin	Placebo
Arm/Group Description	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 arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks.
Period Title: Overall Study
STARTED	9	6
COMPLETED	8	6
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Insulin	Placebo	Total
Arm/Group Description	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 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 of all reporting groups
Overall Participants	8	6	14
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 62.5%	3 50%	8 57.1%
>=65 years	3 37.5%	3 50%	6 42.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.4 (5.7)	62.2 (9.6)	62.9 (7.2)
Sex: Female, Male (Count of Participants)
Female	3 37.5%	3 50%	6 42.9%
Male	5 62.5%	3 50%	8 57.1%
Region of Enrollment (Count of Participants)
United States	8 100%	6 100%	14 100%

Outcome Measures

1. Primary Outcome

Title	Change in Verbal Fluency FAS (F, A or S Words) Total Score
Description	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.
Time Frame	Baseline and post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin Baseline	Insulin Post Treatment	Placebo Baseline	Placebo Post Treatment
Arm/Group Description	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;	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;	FAS score in the placebo group at baseline Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks.	FAS score in the placebo group post treatment Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks
Measure Participants	8	8	6	6
Mean (Standard Deviation) [Words]	38.8 (5.7)	41.0 (8.2)	32.8 (2.3)	30.8 (7.1)

2. Secondary Outcome

Title	Modified Hoehn and Yahr Scale
Description	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.
Time Frame	Baseline and post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin Baseline	Insulin Post Treatment	Placebo Baseline	Placebo Post Treatment
Arm/Group Description	HY Scale in the insulin group at baseline	HY scale in the insulin group post treatment	HY scale in placebo group at baseline	HY scale in placebo group post treatment
Measure Participants	8	8	6	6
Mean (Standard Deviation) [score on a scale]	2.0 (0.6)	2.0 (0.7)	2.4 (0.38)	2.4 (0.2)

3. Secondary Outcome

Title	Cognitive Impairment Using Montreal Cognitive Assessment (MoCA)
Description	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.
Time Frame	Baseline and post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin Baseline	Insulin Post Treatment	Placebo Baseline	Placebo Post Treatment
Arm/Group Description	MOCA Scale in insulin group at baseline	MOCA scale in insulin group post treatment	MOCA score in the placebo group at baseline	MOCA score in the placebo group post treatment
Measure Participants	8	8	6	6
Mean (Standard Deviation) [score on a scale]	28.7 (1.2)	28.0 (1.1)	26.8 (2.6)	28.2 (0.95)

4. Secondary Outcome

Title	Beck Depression Inventory Score (BDI)
Description	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.
Time Frame	Baseline and post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin Baseline	Insulin Post Treatment	Placebo Baseline	Placebo Post Treatment
Arm/Group Description	BDI Scale in the insulin group at baseline	BDI scale in the insulin group post-treatment	BDI score in the placebo group at baseline	BDI score in the placebo group post treatment
Measure Participants	8	8	6	6
Mean (Standard Deviation) [score on a scale]	7.8 (5.4)	8.25 (8.1)	13.5 (5.6)	12.8 (7.4)

5. Other Pre-specified Outcome

Title	Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III)
Description	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.
Time Frame	Baseline and post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin Baseline	Insulin Post Treatment	Placebo Baseline	Placebo Post Treatment
Arm/Group Description	UPDRS III Scale in the insulin group at baseline	UPDRS III Scale in the insulin group at post treatment	UPDRS III Scale in the placebo group at baseline	UPDRS III Scale in the insulin group post treatment
Measure Participants	8	8	6	6
Mean (Standard Deviation) [score on a scale]	31.5 (20.0)	25.6 (21.8)	31.7 (13.3)	30.5 (15.8)

6. Other Pre-specified Outcome

Title	Gait Analysis (4-meter Test)
Description	Changes in gait compared to baseline. Data are reported as changes in average stride interval ( inch) at baseline and post treatment.
Time Frame	Baseline and post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin Baseline	Insulin Post Treatment	Placebo Baseline	Placebo Post Treatment
Arm/Group Description	Stride interval in the insulin group at baseline	Stride interval in the insulin group post treatment	Stride interval in placebo group at baseline	Stride interval in placebo group post treatment
Measure Participants	8	8	6	6
Mean (Standard Deviation) [inch]	22.0 (5.0)	21.5 (4.4)	21.0 (2.7)	19.6 (2.9)

7. Other Pre-specified Outcome

Title	Brief Visuospatial Memory Test-Revised (BVMT-R)
Description	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.
Time Frame	Baseline and post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Insulin		Placebo
Arm/Group Description	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 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.
All Cause Mortality
	Insulin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/6 (0%)
Serious Adverse Events
	Insulin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Insulin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/9 (11.1%)	1	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.