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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 in this double-blinded, placebo-controlled study 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 study is an arm of a previously completed translational pilot biomechanistic target engagement study in older adults with slow walking and/or parkinsonian signs (NCT04325503). This sub-study will further investigate this biomechanistic target engagement using a double-blind, placebo-controlled study design.
The study will include elderly men and women age 60 or older with evidence of mild parkinsonian signs (MPS, or slow gait (< 1m/s)).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Carbidopa Monotherapy and Carbidopa-Levodopa | Experimental | Participants will begin by taking 25mg of Carbidopa monotherapy three times per day (TID) for 3 days. On day four, participants will begin taking 1 tablet of Carbidopa-Levodopa (25/100mg) TID in addition to the Carbidopa monotherapy. On day seven, participants will increase to 1.5 tablets of Carbidopa-Levodopa (25/100mg) TID while maintaining 25mg Carbidopa monotherapy TID. The intervention will end after ten days of supplementation. |
|
| Placebo | Placebo Comparator | Participants will begin by taking a 25mg placebo tablet three times per day (TID) for 3 days. On day four, participants will begin taking a separate placebo tablet TID in addition to the original placebo. On day seven, participants will increase to 1.5 tablets of the second placebo TID while maintaining 25mg original placebo TID. The intervention will end after ten days of supplementation. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carbidopa 25 mg | Drug | Participants will take one 25mg Carbidopa tablet 3 times a day for 10 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Average Gait Speed | Average gait speed as measured using wearable sensors and while walking on a sensor mat. Measured in meters per second. | Baseline and post-intervention (7-13 days after beginning supplement) |
| Measure | Description | Time Frame |
|---|---|---|
| Parkinson's Disease (PD)-Cognitive Rating Scale Score | Cognitive scale designed to capture impairments in cognitive function in Parkinson's disease. (Scoring: 0-134, with higher scores indicating better performance). | Baseline and post-intervention (7-13 days after beginning supplement) |
| Mean of Number of Incorrect Responses on the Stroop Color Word Stepping Test |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Chatkaew Pongmala, PhD | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Domino's Farms | Ann Arbor | Michigan | 48105 | United States | ||
| University Hospital |
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Participants were considered "enrolled" once they signed a consent form. While thirteen participants were consented and therefore enrolled, two failed their screening post-consent.
Eleven were randomized and participated in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Carbidopa Monotherapy and Carbidopa-Levodopa | Participants will begin by taking 25mg of Carbidopa monotherapy three times per day (TID) for 3 days. On day four, participants will begin taking 1 tablet of Carbidopa-Levodopa (25/100mg) TID in addition to the Carbidopa monotherapy. On day seven, participants will increase to 1.5 tablets of Carbidopa-Levodopa (25/100mg) TID while maintaining 25mg Carbidopa monotherapy TID. The intervention will end after ten days of supplementation. Carbidopa 25 mg: Participants will take one 25mg Carbidopa tablet 3 times a day for 10 days. Carbidopa-Levodopa 25/100 mg: Participants will take one 25/100mg carbidopa-levodopa tablet 3 times a day on days 4-6, then increase to 1.5 tablets 3 times a day on days 7-10. |
| FG001 | Placebo | Participants will begin by taking a 25mg placebo tablet three times per day (TID) for 3 days. On day four, participants will begin taking a separate placebo tablet TID in addition to the original placebo. On day seven, participants will increase to 1.5 tablets of the second placebo TID while maintaining 25mg original placebo TID. The intervention will end after ten days of supplementation. Placebo 1: Participants will take one 25mg placebo tablet 3 times a day for 10 days. Placebo 2: Participants will take one 100mg placebo tablet 3 times a day on days 4-6, then increase to 1.5 tablets 3 times a day on days 7-10. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Carbidopa Monotherapy and Carbidopa-Levodopa | Participants will begin by taking 25mg of Carbidopa monotherapy three times per day (TID) for 3 days. On day four, participants will begin taking 1 tablet of Carbidopa-Levodopa (25/100mg) TID in addition to the Carbidopa monotherapy. On day seven, participants will increase to 1.5 tablets of Carbidopa-Levodopa (25/100mg) TID while maintaining 25mg Carbidopa monotherapy TID. The intervention will end after ten days of supplementation. Carbidopa 25 mg: Participants will take one 25mg Carbidopa tablet 3 times a day for 10 days. Carbidopa-Levodopa 25/100 mg: Participants will take one 25/100mg carbidopa-levodopa tablet 3 times a day on days 4-6, then increase to 1.5 tablets 3 times a day on days 7-10. |
| 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 and while walking on a sensor mat. Measured in meters per second. | Posted | Mean | Standard Deviation | meters per second | Baseline and post-intervention (7-13 days after beginning supplement) |
|
13 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 Monotherapy and Carbidopa-Levodopa | Participants will begin by taking 25mg of Carbidopa monotherapy three times per day (TID) for 3 days. On day four, participants will begin taking 1 tablet of Carbidopa-Levodopa (25/100mg) TID in addition to the Carbidopa monotherapy. On day seven, participants will increase to 1.5 tablets of Carbidopa-Levodopa (25/100mg) TID while maintaining 25mg Carbidopa monotherapy TID. The intervention will end after ten days of supplementation. Carbidopa 25 mg: Participants will take one 25mg Carbidopa tablet 3 times a day for 10 days. Carbidopa-Levodopa 25/100 mg: Participants will take one 25/100mg carbidopa-levodopa tablet 3 times a day on days 4-6, then increase to 1.5 tablets 3 times a day on days 7-10. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Principle Investigator | University of Michigan | 734-998-8400 | pchatkae@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 | Dec 17, 2024 | May 27, 2025 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 22, 2024 | Jun 13, 2025 | ICF_002.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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| Carbidopa-Levodopa 25/100 mg | Drug | Participants will take one 25/100mg carbidopa-levodopa tablet 3 times a day on days 4-6, then increase to 1.5 tablets 3 times a day on days 7-10. |
|
|
| Placebo 1 | Drug | Participants will take one 25mg placebo tablet 3 times a day for 10 days. |
|
| Placebo 2 | Drug | Participants will take one 100mg placebo tablet 3 times a day on days 4-6, then increase to 1.5 tablets 3 times a day on days 7-10. |
|
During this test, subjects make steps based on congruent (stimulus prompts the stepping response) and incongruent (stimulus prompts inhibition of the stepping response) arrows and sounds. This will be used to compare the number of incorrect responses (stepping) from pre and post intervention visits to determine if inhibitory control improves (indicated by decrease in number of incorrect responses). The test included 8 total opportunities for response. |
| Baseline and post-intervention (7-13 days after beginning supplement) |
| Mean of Reaction Time During the Stroop Color Word Stepping Test | During this test, subjects make steps based on congruent (stimulus prompts the stepping response) and incongruent (stimulus prompts inhibition of the stepping response) arrows and sounds. This will be used to compare the response time between pre and post intervention to determine if reaction time improves. | Baseline and post-intervention (7-13 days after beginning supplement) |
| Ann Arbor |
| Michigan |
| 48109 |
| United States |
| BG001 | Placebo | Participants will begin by taking a 25mg placebo tablet three times per day (TID) for 3 days. On day four, participants will begin taking a separate placebo tablet TID in addition to the original placebo. On day seven, participants will increase to 1.5 tablets of the second placebo TID while maintaining 25mg original placebo TID. The intervention will end after ten days of supplementation. Placebo 1: Participants will take one 25mg placebo tablet 3 times a day for 10 days. Placebo 2: Participants will take one 100mg placebo tablet 3 times a day on days 4-6, then increase to 1.5 tablets 3 times a day on days 7-10. |
| BG002 | Total | Total of all reporting groups |
| 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 |
|
| OG001 | Placebo | Participants will begin by taking a 25mg placebo tablet three times per day (TID) for 3 days. On day four, participants will begin taking a separate placebo tablet TID in addition to the original placebo. On day seven, participants will increase to 1.5 tablets of the second placebo TID while maintaining 25mg original placebo TID. The intervention will end after ten days of supplementation. Placebo 1: Participants will take one 25mg placebo tablet 3 times a day for 10 days. Placebo 2: Participants will take one 100mg placebo tablet 3 times a day on days 4-6, then increase to 1.5 tablets 3 times a day on days 7-10. |
|
|
| Secondary | Parkinson's Disease (PD)-Cognitive Rating Scale Score | Cognitive scale designed to capture impairments in cognitive function in Parkinson's disease. (Scoring: 0-134, with higher scores indicating better performance). | Posted | Mean | Standard Deviation | score on a scale | Baseline and post-intervention (7-13 days after beginning supplement) |
|
|
|
| Secondary | Mean of Number of Incorrect Responses on the Stroop Color Word Stepping Test | During this test, subjects make steps based on congruent (stimulus prompts the stepping response) and incongruent (stimulus prompts inhibition of the stepping response) arrows and sounds. This will be used to compare the number of incorrect responses (stepping) from pre and post intervention visits to determine if inhibitory control improves (indicated by decrease in number of incorrect responses). The test included 8 total opportunities for response. | Posted | Mean | Standard Deviation | Incorrect Responses | Baseline and post-intervention (7-13 days after beginning supplement) |
|
|
|
| Secondary | Mean of Reaction Time During the Stroop Color Word Stepping Test | During this test, subjects make steps based on congruent (stimulus prompts the stepping response) and incongruent (stimulus prompts inhibition of the stepping response) arrows and sounds. This will be used to compare the response time between pre and post intervention to determine if reaction time improves. | Posted | Mean | Standard Deviation | seconds | Baseline and post-intervention (7-13 days after beginning supplement) |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 3 |
| 6 |
| EG001 | Placebo | Participants will begin by taking a 25mg placebo tablet three times per day (TID) for 3 days. On day four, participants will begin taking a separate placebo tablet TID in addition to the original placebo. On day seven, participants will increase to 1.5 tablets of the second placebo TID while maintaining 25mg original placebo TID. The intervention will end after ten days of supplementation. Placebo 1: Participants will take one 25mg placebo tablet 3 times a day for 10 days. Placebo 2: Participants will take one 100mg placebo tablet 3 times a day on days 4-6, then increase to 1.5 tablets 3 times a day on days 7-10. | 0 | 5 | 0 | 5 | 3 | 5 |
| Blood pressure fluctuations | Cardiac disorders | Systematic Assessment |
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| Claustrophobia during MRI | Psychiatric disorders | Systematic Assessment |
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| Mild Confusion | Psychiatric disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Dizziness | General disorders | Systematic Assessment |
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| Drowsiness | General disorders | Systematic Assessment |
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| Toe injury | Injury, poisoning and procedural complications | Systematic Assessment | Unrelated to study intervention |
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| Muscle Strain | Injury, poisoning and procedural complications | Systematic Assessment | Unrelated to study intervention |
|
| Joint Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment | Unrelated to study intervention |
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| D009930 |
| Organic Chemicals |
| D006834 | Hydrazines |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |