Parkinsonian Signs in Older PersonsPhase 1/2RESNCT04325503
Neurobiological Drivers of Mobility Resilience: The Dopaminergic System
A Phase 1/2 study testing carbidopa in people with Parkinsonian Signs in Older Persons, run by University of Michigan at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Parkinsonian Signs in Older Persons
- What is being tested?
- carbidopa
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Feb 2021to 30 Jun 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 60 or older (M/F)
- Evidence of mild parkinsonian signs (incl. slow gait (< 1m/s))
Who cannot join
- Presence of clinically significant degenerative joint disease and/or neuropathy interfering with proper assessment of the motor UPDRS exam.
- Presence of significant dementia.
- Evidence of a large vessel stroke in a clinically relevant area (cerebral cortex, basal ganglia, thalamus) or mass lesion on structural brain imaging (MRI).
- Participants in whom magnetic resonance imaging (MRI) is contraindicated including, but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord, or cochlear implant.
- Severe claustrophobia precluding neuroimaging procedures.
- Hypersensitivity to the carbidopa, levodopa, and tablet components.
- Any other medical history determined by investigators to preclude safe participation.
Trial locations and contacts
1 site in 1 country.
United States1 site
Functional Neuroimaging, Cognitive, and Mobility Lab, University of Michigan
Ann Arbor, Michigan, 48105
About this study
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.
Read the detailed description
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.
- Conditions
- Parkinsonian Signs in Older Persons
- Being tested
- carbidopa
- Keywords
- slow gait, Parkinsonian signs
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
carbidopaDrug
Also called carbidopa-levodopa
carbidopa and carbidopa-levodopa standard treatment
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | carbidopa and carbidopa-levodopa treatment for parkinsonian signs in older persons using standard dosing, frequency for a duration for 1-2 weeks Receives: Drug: carbidopa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average Gait Speed
Average gait speed as measured using wearable sensors worn during walking tasks. Gait speed is measured in meters per second.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 7-13 days after beginning treatment
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.
Measured: 7-13 days after beginning treatment
Secondary outcomes (1)
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.
Measured: 7-13 days after beginning treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2020
- Study start8 Feb 2021
- Primary completion30 Jun 2022
- Study completion30 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Parkinsonian Signs in Older PersonsStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Nicolaas Bohnen, MD, PhD, University of Michigan
- Investigators
- Nicolaas Bohnen, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04325503
- Sponsor's protocol ID
- HUM00156490
- Other IDs
- 5U01AG061393-05
- Acronym
- RES
- Status last verified
- Apr 2024
- First submitted
- 24 Mar 2020
- Last updated
- 4 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Results will be provided in publications
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurobiological Drivers of Mobility Resilience: The Dopaminergic System
- ClinicalTrials.gov ID
- NCT04325503
- Acronym / sponsor ID
- RES / HUM00156490
- Conditions
- Parkinsonian Signs in Older Persons
- Keywords
- slow gait, Parkinsonian signs
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 8 Feb 2021 (actual)
- Primary completion
- 30 Jun 2022 (actual)
- Study completion
- 30 Jun 2022 (actual)
- First posted
- 27 Mar 2020 (actual)
- Results
- Posted 28 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: carbidopacarbidopa and carbidopa-levodopa treatment for parkinsonian signs in older persons using standard dosing, frequency for a duration for 1-2 weeks |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age 60 or older (M/F)
- Evidence of mild parkinsonian signs (incl. slow gait (< 1m/s))
Key exclusion criteria (7 listed)
- Presence of clinically significant degenerative joint disease and/or neuropathy interfering with proper assessment of the motor UPDRS exam.
- Presence of significant dementia.
- Evidence of a large vessel stroke in a clinically relevant area (cerebral cortex, basal ganglia, thalamus) or mass lesion on structural brain imaging (MRI).
- Participants in whom magnetic resonance imaging (MRI) is contraindicated including, but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord, or cochlear implant.
- Severe claustrophobia precluding neuroimaging procedures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| carbidopaAlso: carbidopa-levodopacarbidopa and carbidopa-levodopa standard treatment | Drug | Treatment |
Primary outcome
Average Gait Speed
Time frame: 7-13 days after beginning treatment.
Average gait speed as measured using wearable sensors worn during walking tasks. Gait speed is measured in meters per second.
Montreal Cognitive Assessment (MoCA)
Time frame: 7-13 days after beginning treatment
Cognitive assessment used to evaluate individuals for mild cognitive impairment. Scores range from 0-30. Higher scores indicate better performance.
Mini Balance Evaluation Systems Test (Mini-BESTest)
Time frame: 7-13 days after beginning treatment
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.
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total
Time frame: 7-13 days after beginning treatment
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.
Cognitive Z-score
Time frame: 7-13 days after beginning treatment
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.
Wechsler Adult Intelligence System Digit Symbol Substitution Test
Time frame: 7-13 days after beginning treatment
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.
1 secondary outcome
Short Activities-specific Balance Confidence Scale Score
Time frame: 7-13 days after beginning treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Results will be provided in publications
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicolaas Bohnen, MD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing carbidopa in people with Parkinsonian Signs in Older Persons, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average Gait Speed (time frame: 7-13 days after beginning treatment.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2024.