This project will investigate exploratory outcomes related to the effect of intranasal insulin on cognition, mood, apathy and motor performance of subjects with Parkinson's disease over a 3 week period.
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's dementia and was originally described as a motor disease. The diagnosis of PD is still based on the core motor features of bradykinesia, resting tremor, and rigidity, primarily as a result of degeneration of nigrostriatal dopaminergic neurons. In addition to the classic motor symptoms, however, PD is increasingly recognized as a multisystem disorder. A variety of non-motor symptoms, including cognitive deficits and dementia, are commonly observed in patients with PD. In this study, we aim to investigate which intranasal insulin dose out of three doses and placebo, administered at three different doses or placebo over a 21-day period, is the optimum dosage based on safety and tolerability in Parkinson's disease. A similar design was used in a trial investigating intranasal oxytocin in frontotemporal dementia. Dosing for the first two groups of this study is based on previously conducted intranasal insulin studies in Alzheimer's disease (AD) and mild cognitive impairment (MCI), using daily doses on 20 and 40 IU of intranasal insulin. Higher dose have been found to be safe in healthy adults. Prior studies performed have demonstrated favorable effects of this regimen in the MCI/AD population without peripheral hypoglycemia.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
31
Intranasal insulin
Intranasal placebo (0.9% saline)
HealthPartners Neuroscience Center
Saint Paul, Minnesota, United States
Safety Measured by Count of Safety Events
Composite safety event - this is a count of either a reduction of fasting glucose to \<70 mg/dL or an unintended reduction of weight \>5%. A larger composite event count indicates a less safe treatment.
Time frame: 3 weeks
Safety Measured by Fasting Glucose
Pre-post change in fasting glucose (mg/dL). A larger decrease in fasting glucose indicates a less safe treatment.
Time frame: baseline and 3 weeks
Safety Measured by Body Weight
Pre-post change in body weight (lbs). An unintended decrease in body weight indicates a less safe treatment.
Time frame: baseline and 3 weeks
Safety Measured by the Number of Serious Adverse Events (SAE) and Adverse Events (AE)
Total number of AEs/SAEs during the course of treatment. More AEs/SAEs indicates a less safe treatment.
Time frame: 3 weeks
Cognitive Function Measured by the Montreal Cognitive Assessment (MoCA)
Pre-post difference. Total sum of scores. Range: 0-30. Higher score indicates less memory loss
Time frame: 5 weeks
Cognitive Function Measured by the Weschler Adult Intelligence Scale - Fourth Edition (WAIS-IV) Digit Span
Pre-post difference. Scaled score. Range: 1-19. Forward and backward. Lower score indicates more impairment.
Time frame: 3 weeks
Cognitive Function Measured by the Trailmaking Test Part A Time
Pre-post difference. T-score. Mean: 50, Standard deviation: 10. A higher T-score indicates a better outcome/performance. Clinically, 1-1.5 standard deviations would be significant, 2 standard deviations would be considered abnormal/impaired.
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Time frame: baseline and 3 weeks
Cognitive Function Measured by the Trailmaking Test Part B Time
Pre-post difference. T-score. Mean: 50, Standard deviation: 10. A higher T-score indicates a better outcome/performance. Clinically, 1-1.5 standard deviations would be significant, 2 standard deviations would be considered abnormal/impaired.
Time frame: baseline and 3 weeks
Cognitive Function Measured by the Trailmaking Test Parts A & B Errors
Pre-post difference. Total number of errors. No range. More errors indicate more impairment.
Time frame: 3 weeks
Cognitive Function Measured by the Judgement of Line Orientation
Judgement of Line Orientation is an assessment of visuospatial ability. A Z-score of 0 represents the population mean. Pre-post difference. A positive difference indicates an improvement.
Time frame: baseline and 3 weeks
Cognitive Function Measured by the Logical Memory Scaled Scores
Pre-post difference. Scaled score. Range: 1-19. Logical memory immediate and delayed. Lower score indicates more impairment.
Time frame: baseline and 3 weeks
Cognitive Function Measured by the Logical Memory, Recognition
Pre-post difference in median category from baseline to 3 weeks on the Logical memory, recognition subscale. Scoring of this and all outcomes were based on best practices conveyed by study neuropsychologist during study design, and scoring approaches were chosen completely a priori. The recognition outcome of the LM test is derived from a series of conversions, as follows. First, the raw "process" score is converted to cumulative percentage (0-100). Because the cumulative percentage distribution is known to be skewed, best practice is to report scores as the following ordinal categorizations of cumulative percentages: \<1, 3-9, 10-16, 17-25, 26-50, 51-75, and \>75. To analyze them using simple statistics, these ordinal categories are converted to integer values (1-7), and the change in median ordinal category is presented along with 95% confidence intervals, generated by the Wilcoxon signed rank test with continuity correction.
Time frame: baseline and 3 weeks
Cognitive Function Measured by the Hopkins Verbal Learning Test - Revised (HVLT)
Pre-post difference. T-score. Mean: 50, Standard deviation: 10. A higher T-score indicates a better outcome/performance. Clinically, 1-1.5 standard deviations would be significant, 2 standard deviations would be considered abnormal/impaired.
Time frame: baseline and 3 weeks
Cognitive Function Measured by the Visuospatial Memory Test - Revised (BVMT)
Pre-post difference. T-score. Mean: 50, Standard deviation: 10. A higher T-score indicates a better outcome/performance. Clinically, 1-1.5 standard deviations would be significant, 2 standard deviations would be considered abnormal/impaired.
Time frame: 3 weeks
Cognitive Function Measured by the Stroop Color Word Test (CWT)
Pre-post difference. T-score. Mean: 50, Standard deviation: 10. A higher T-score indicates a better outcome/performance. Clinically, 1-1.5 standard deviations would be significant, 2 standard deviations would be considered abnormal/impaired.
Time frame: baseline and 3 weeks
Cognitive Function Measured by Fluency
Pre-post difference. T-score. Mean: 50, Standard deviation: 10. A higher T-score indicates a better outcome/performance. Clinically, 1-1.5 standard deviations would be significant, 2 standard deviations would be considered abnormal/impaired.
Time frame: baseline and 3 weeks
Mood Measured by the Beck Depression Inventory - Second Edition
Pre-post difference. Raw score. Range: 0-63. Higher score indicates more symptomatic.
Time frame: baseline and 3 weeks
Apathy Measured by the Apathy Scale
Pre-post difference. Raw score. Range: 0-42. Higher score indicates more symptomatic.
Time frame: baseline and 3 weeks
Mood Measured by the Columbia Suicide Severity Rating (C-SSRS)
Pre-post difference. Raw score. Range:1 or 0. 1 score - more symptomatic, 0 score - no symptoms.
Time frame: baseline and 3 weeks
Motor Function as Measured by the United Parkinson's Disease Rating Scale (UPDRS-III)
Pre-post difference. Raw score. Range: 0-72. Higher score indicates more symptomatic.
Time frame: baseline and 3 weeks
Cognitive Function Measured by Visuospatial Memory Test - Revised (BVMT Recognition)
Pre-post difference in median category from baseline to 3 weeks on the Brief Visual Spatial Memory Test - Revised recognition. Scoring of this and all outcomes were based on best practices conveyed by study neuropsychologist during study design, and scoring approaches were chosen completely a priori. The recognition outcome of the BVMT test is derived from a series of conversions, as follows. First, the raw score is converted to cumulative percentage (0-100). Because the cumulative percentage distribution is known to be skewed, best practice is to report scores as the following ordinal categorizations of cumulative percentages: \<2, 2-5, 6-10, 11-16, \>16. To analyze them using simple statistics, these ordinal categories are converted to integer values (1-5), and the change in median ordinal category is presented along with 95% confidence intervals, generated by the Wilcoxon signed rank test with continuity correction.
Time frame: baseline and 3 weeks