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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Insulin | Experimental | 40 IU of intranasal insulin daily |
|
| Placebo | Placebo Comparator | Placebo arm using intranasal normal saline |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intranasal Insulin | Drug |
|
|
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) | 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Peter Novak', MD,PhD | Former Associate Professor | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Massachusetts Medical School | Worcester | Massachusetts | 01655 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31022213 | Derived | Novak P, Pimentel Maldonado DA, Novak V. Safety and preliminary efficacy of intranasal insulin for cognitive impairment in Parkinson disease and multiple system atrophy: A double-blinded placebo-controlled pilot study. PLoS One. 2019 Apr 25;14(4):e0214364. doi: 10.1371/journal.pone.0214364. eCollection 2019. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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; |
| FG001 | Placebo | Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | Words | Baseline and post-treatment |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Peter Novak, MD PhD | Brigham & Women's Hospital | 617-732-8896 | pnovak2@bwh.harvard.edu |
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| D019578 | Multiple System Atrophy |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D007328 | Insulin |
| ID | Term |
|---|---|
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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|
| 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 |
| Baseline and post-treatment |
| Gait Analysis (4-meter Test) | Changes in gait compared to baseline. Data are reported as changes in average stride interval ( inch) at baseline and post treatment. | Baseline and post-treatment |
| Brief Visuospatial Memory Test-Revised (BVMT-R) | 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. | Baseline and post-treatment |
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.
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Insulin Post Treatment |
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; |
| OG002 | Placebo Baseline | FAS score in the placebo group at baseline Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks. |
| OG003 | Placebo Post Treatment | FAS score in the placebo group post treatment Placebo arm using intranasal normal saline Placebo arm: normal saline, daily, intranasally, for 4 weeks |
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline and post-treatment |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline and post-treatment |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline and post-treatment |
|
|
|
| Other Pre-specified | Unified Parkinson's Disease Rating Scale Part III (UPDRS Part III) | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline and post-treatment |
|
|
|
| Other Pre-specified | Gait Analysis (4-meter Test) | Changes in gait compared to baseline. Data are reported as changes in average stride interval ( inch) at baseline and post treatment. | Posted | Mean | Standard Deviation | inch | Baseline and post-treatment |
|
|
|
| Other Pre-specified | Brief Visuospatial Memory Test-Revised (BVMT-R) | 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. | Not Posted | Baseline and post-treatment | Participants |
| 0 |
| 9 |
| 0 |
| 9 |
| 1 |
| 9 |
| EG001 | 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. | 0 | 6 | 0 | 6 | 0 | 6 |
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| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D054969 | Primary Dysautonomias |
| D001342 | Autonomic Nervous System Diseases |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |