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| ID | Type | Description | Link |
|---|---|---|---|
| 5U01AG061393-05 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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Walking with age becomes both slower and less 'automated', requiring more attention and brain resources. As a result, older adults have a greater risk of negative outcomes and falls. There is an urgent need to identify factors that can help compensate for these harmful factors and reduce walking impairments, as there are currently no effective treatments available. Investigators have recently discovered that ~20% of older adults maintain fast walking speed even in the presence of small blood vessel brain changes and leg problems, thus appearing to be protected against these harmful factors. The investigators work suggests that the brain dopamine (DA) system may be a source of this protective capacity. Investigators have also shown that lower levels of dopamine are associated with slow walking. Investigators will be investigating the role of dopamine on slow walking and other parkinsonian signs using detailed clinical assessment, assessment of dopamine activity, and clinical interventions.
Walking with age becomes both slower and less 'automated', requiring more attention and prefrontal resources. As a result older adults have a greater risk of adverse mobility outcomes and falls. Walking disturbances in the elderly have been linked to changes in both cerebral, in particular small vessel disease (cSVD), and peripheral systems. There is an urgent need to identify factors that can help compensate for these harmful factors and reduce walking impairments, as there are currently no effective treatments available. Although effective mobility is the end result of the functional capacity of both central and peripheral systems, the brain's unique modulatory and adaptive capacity may provide clues for novel interventions. For example, investigators have recently discovered that ~20% of older adults maintain fast walking speed even in the presence of age related cSVD and peripheral system impairments, thus appearing resilient to these harmful factors. The investigators work suggests that the nigrostriatal dopamine (DA) system may be a source of this resilience. As investigators recent findings suggest, DA neurotransmission positively predicts walking speed; it also attenuates the negative effects of age related cSVD and peripheral system impairments on walking speed. These findings are consistent with post-mortem evidence that a combination of loss of nigral DA neurons and cSVD best predict age-related walking impairment. The nigrostriatal DA system plays a critical role in motor control; nigrostriatal. DA neurotransmission regulates the automated execution of overlearned motor tasks via its connections with sensorimotor cortical and subcortical areas.
The investigators hypothesize that higher nigrostriatal DA neurotransmission drives resilience to cSVD and peripheral system impairments, via higher connectivity of sensorimotor networks, thus increasing automaticity of walking and reducing prefrontal engagement while walking. Unlike cSVD and brain structural impairments, DA neurotransmission is potentially modifiable, thereby offering novel approaches to treat non-resilient elderly in a targeted fashion. This translational pilot study will use a biomechanistic target engagement study in older adults with slow walking and/or other parkinsonian signs.
The study will include elderly men and women age 60 or older with evidence of mild parkinsonian signs (MPS, or slow gait (< 1m/s)) and/or additional cSVD on brain MRI.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment | Experimental | carbidopa and carbidopa-levodopa treatment for parkinsonian signs in older persons using standard dosing, frequency for a duration for 1-2 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| carbidopa | Drug | carbidopa and carbidopa-levodopa standard treatment |
|
| Measure | Description | Time Frame |
|---|---|---|
| Average Gait Speed | Average gait speed as measured using wearable sensors worn during walking tasks. Gait speed is measured in meters per second. | 7-13 days after beginning treatment. |
| Montreal Cognitive Assessment (MoCA) | Cognitive assessment used to evaluate individuals for mild cognitive impairment. Scores range from 0-30. Higher scores indicate better performance. | 7-13 days after beginning treatment |
| Mini Balance Evaluation Systems Test (Mini-BESTest) | The mini-BESTest is a 14-item evaluation of dynamic balance and postural control. It is scored from 0-28, with higher scores indicating better performance. | 7-13 days after beginning treatment |
| Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total | MDS-UPDRS part III is the motor examination portion of the UPDRS evaluation. Scores range from 0-132, with higher scores indicating greater severity of motor symptoms. | 7-13 days after beginning treatment |
| Cognitive Z-score | Composite variable calculated based on the Stroop Color Word Interference test I-IV (assessment of attention) and Delis-Kaplan Executive Function System Trail Making test I-V (assessment of executive function and working memory), adjusted based on normative data for older adults. A z-score of 0 represents the control population mean. Scores above the mean indicate better performance, while scores below the mean indicate poorer performance. | 7-13 days after beginning treatment |
| Wechsler Adult Intelligence System Digit Symbol Substitution Test |
| Measure | Description | Time Frame |
|---|---|---|
| Short Activities-specific Balance Confidence Scale Score | Participants rate their level of confidence in doing specific activities without losing their balance as a percentage, with 0% indicating they are certain they would lose their balance and 100% indicating that they are certain they can complete the task without losing their balance. Scores on these 6 questions are averaged to determine total sABC score. Scores range from 0-100, with higher scores indicating greater balance confidence. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nicolaas Bohnen, MD | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Functional Neuroimaging, Cognitive, and Mobility Lab, University of Michigan | Ann Arbor | Michigan | 48105 | United States |
Results will be provided in publications
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| ID | Title | Description |
|---|---|---|
| FG000 | Carbidopa and Carbidopa-Levodopa Treatment | All participants treated with 25 mg carbidopa three times daily (TID) and 1.5 pills of 25/100 mg carbidopa-levodopa TID for parkinsonian signs in older persons (standard dosing, frequency for a duration for 1-2 weeks). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment | carbidopa and carbidopa-levodopa treatment for parkinsonian signs in older persons using standard dosing, frequency for a duration for 1-2 weeks carbidopa: carbidopa and carbidopa-levodopa standard treatment |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Average Gait Speed | Average gait speed as measured using wearable sensors worn during walking tasks. Gait speed is measured in meters per second. | Gait speed data was missing for one participant due to software error. | Posted | Mean | Standard Deviation | meters/second | 7-13 days after beginning treatment. |
|
|
Up to 14 days
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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 | Carbidopa and Carbidopa-Levodopa Treatment | All participants treated with 25 mg carbidopa three times daily (TID) and 1.5 pills of 25/100 mg carbidopa-levodopa TID for parkinsonian signs in older persons (standard dosing, frequency for a duration for 1-2 weeks). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Systematic Assessment | Mild, expected Adverse event (AE). |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nicolaas Bohnen | Unversity of Michigan | 734-998-8400 | nbohnen@umich.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 21, 2020 | Jul 31, 2023 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 11, 2022 | Sep 12, 2022 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D002230 | Carbidopa |
| C009265 | carbidopa, levodopa drug combination |
| ID | Term |
|---|---|
| D008750 | Methyldopa |
| D004295 | Dihydroxyphenylalanine |
| D002395 | Catecholamines |
| D000588 | Amines |
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Evaluation of cognitive functioning in which a participant is given a key of numbers 1-9, each paired with a unique symbol. Below the key, is a series of random numbers which they participant must fill in the corresponding symbol for. They have 120 seconds to complete the task. Participants receive one point for each correct symbol written. Score range from 0-133.
| 7-13 days after beginning treatment |
| 7-13 days after beginning treatment |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Average Gait Speed | Average gait speed as measured using wearable sensors worn during walking tasks. Gait speed is measured in meters per second. | Average gait speed was not collected for 3 participants because they withdrew (Two participants were withdrawn from the study due to lack of motor symptoms. One participant withdrew from study due to personal time constraints). Gait data was not collected for one participant due to software error. | Mean | Standard Deviation | meters/second |
|
| Montreal Cognitive Assessment (MoCA) Score | Cognitive assessment used to evaluate individuals for mild cognitive impairment. Scores range from 0-30. Higher scores indicate better performance. | MoCA was not collected for 3 participants because they withdrew from the study (two participants were withdrawn from the study due to lack of motor symptoms. One participant withdrew from study due to personal time constraints). | Mean | Standard Deviation | score on a scale |
|
| Mini Balance Evaluation Systems Test (Mini-BESTest) | The mini-BESTest is a 14-item evaluation of dynamic balance and postural control. It is scored from 0-28, with higher scores indicating better performance. | Mini-BESTest was not collected for 3 participants because they withdrew from the study (two participants were withdrawn from the study due to lack of motor symptoms. One participant withdrew from study due to personal time constraints). | Mean | Standard Deviation | score on a scale |
|
| Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III total | MDS-UPDRS part III is the motor examination portion of the UPDRS evaluation. Scores range from 0-132, with higher scores indicating greater severity of motor symptoms. | Mean | Standard Deviation | units on a scale |
|
| Short Activities-specific Balance Confidence (sABC) scale score | Participants rate their level of confidence in doing specific activities without losing their balance as a percentage, with 0% indicating they are certain they would lose their balance and 100% indicating that they are certain they can complete the task without losing their balance. Scores on these 6 questions are averaged to determine total sABC score. Scores range from 0-100, with higher scores indicating greater balance confidence. | sABC was not collected for 3 participants because they withdrew from the study (two participants were withdrawn from the study due to lack of motor symptoms. One participant withdrew from study due to personal time constraints). One participant did not complete questionnaire due to tech error. | Median | Full Range | score on a scale |
|
| Cognitive z-score | Composite variable calculated based on the Stroop Color Word Interference test I-IV (assessment of attention) and Delis-Kaplan Executive Function System Trail Making test I-V (assessment of executive function and working memory), adjusted based on normative data for older adults. A z-score of 0 represents the control population mean. Scores above the mean indicate better performance, while scores below the mean indicate poorer performance. | Cognitive z-scores were not collected for 3 participants because they withdrew from the study (two participants were withdrawn from the study due to lack of motor symptoms. One participant withdrew from study due to personal time constraints). One participant did not complete all cognitive testing due to language barrier. | Mean | Standard Deviation | Z-score |
|
| Wechsler Adult Intelligence Scale Digit Symbol Test Score | Evaluation of cognitive functioning in which a participant is given a key of numbers 1-9, each paired with a unique symbol. Below the key, is a series of random numbers which they participant must fill in the corresponding symbol for. They have 120 seconds to complete the task. Participants receive one point for each correct symbol written. Score range from 0-133. | The digit symbol test was not collected for 3 participants because they withdrew from the study (two participants were withdrawn from the study due to lack of motor symptoms. One participant withdrew from study due to personal time constraints). Two participants did not complete testing due to tech error. | Mean | Standard Deviation | score on a scale |
|
| Participants |
|
|
|
| Primary | Montreal Cognitive Assessment (MoCA) | Cognitive assessment used to evaluate individuals for mild cognitive impairment. Scores range from 0-30. Higher scores indicate better performance. | Two participants did not complete the MoCA during the follow-up visit due to time constraints. | Posted | Mean | Standard Deviation | score on a scale | 7-13 days after beginning treatment |
|
|
|
|
| Primary | Mini Balance Evaluation Systems Test (Mini-BESTest) | The mini-BESTest is a 14-item evaluation of dynamic balance and postural control. It is scored from 0-28, with higher scores indicating better performance. | Testing was not completed for two participants due to time constraints. | Posted | Mean | Standard Deviation | score on a scale | 7-13 days after beginning treatment |
|
|
|
|
| Primary | Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total | MDS-UPDRS part III is the motor examination portion of the UPDRS evaluation. Scores range from 0-132, with higher scores indicating greater severity of motor symptoms. | Posted | Mean | Standard Deviation | units on a scale | 7-13 days after beginning treatment |
|
|
|
|
| Primary | Cognitive Z-score | Composite variable calculated based on the Stroop Color Word Interference test I-IV (assessment of attention) and Delis-Kaplan Executive Function System Trail Making test I-V (assessment of executive function and working memory), adjusted based on normative data for older adults. A z-score of 0 represents the control population mean. Scores above the mean indicate better performance, while scores below the mean indicate poorer performance. | Data was not collected for 3 participants (one participant did not complete Stroop Color Word Interference tests due to language barrier. One participant did not complete cognitive assessments due to poor vision interfering with test-taking ability. One participant did not complete cognitive testing due to time constraints). | Posted | Mean | Standard Deviation | Z-score | 7-13 days after beginning treatment |
|
|
|
|
| Primary | Wechsler Adult Intelligence System Digit Symbol Substitution Test | Evaluation of cognitive functioning in which a participant is given a key of numbers 1-9, each paired with a unique symbol. Below the key, is a series of random numbers which they participant must fill in the corresponding symbol for. They have 120 seconds to complete the task. Participants receive one point for each correct symbol written. Score range from 0-133. | Two participants did not complete testing due to time constraints | Posted | Mean | Standard Deviation | score on a scale | 7-13 days after beginning treatment |
|
|
|
|
| Secondary | Short Activities-specific Balance Confidence Scale Score | Participants rate their level of confidence in doing specific activities without losing their balance as a percentage, with 0% indicating they are certain they would lose their balance and 100% indicating that they are certain they can complete the task without losing their balance. Scores on these 6 questions are averaged to determine total sABC score. Scores range from 0-100, with higher scores indicating greater balance confidence. | Posted | Median | Full Range | score on a scale | 7-13 days after beginning treatment |
|
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|
|
| 0 |
| 14 |
| 0 |
| 14 |
| 8 |
| 14 |
|
| Vivid dreams | General disorders | Systematic Assessment | Mild, expected AE. |
|
| Mild Changes to Bowel Movement | Gastrointestinal disorders | Systematic Assessment | Mild, expected AE. |
|
| Mild Nasal Congestion | General disorders | Systematic Assessment | Mild, unexpected AE. |
|
| Anxiety | Psychiatric disorders | Systematic Assessment | Mild, expected AE. |
|
| Headache | General disorders | Systematic Assessment | Mild, expected AE. |
|
| Change in Blood Glucose Level | Metabolism and nutrition disorders | Systematic Assessment |
|
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| D009930 |
| Organic Chemicals |
| D006834 | Hydrazines |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |