Parkinsonian Signs in Older PersonsPhase 1/2RESNCT06219915
Neurobiological Drivers of Mobility Resilience: The Dopaminergic System - Placebo-Controlled Arm
A Phase 1/2 study testing Carbidopa 25 mg and Carbidopa-Levodopa 25/100 mg in people with Parkinsonian Signs in Older Persons, run by University of Michigan at 2 sites 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 25 mg and Carbidopa-Levodopa 25/100 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 2 sitesUnited States
- Study dates
- 15 Mar 2024to 30 May 2024
- 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
- Evidence of prior established diagnosis and/or treatment for PD.
- Presence of clinically significant degenerative joint disease and/or neuropathy interfering with proper assessment of the motor exam.
- Presence of significant dementia.
- History of stroke with residual clinical deficit interfering with walking.
- For optional MR imaging only: 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.
- For optional brain imaging only: Severe claustrophobia precluding neuroimaging procedures.
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- Participants that have been on monoamine oxidase inhibitors (MAOIs) within 2 weeks prior to starting study.
- Inability to stand or walk without an assistive device
- Hypersensitivity to the carbidopa, levodopa, and tablet components.
- History of myocardial infarction (MI) with residual arterial, nodal or ventricular arrhythmia
- History of peptic ulcer
- Chronic wide angle glaucoma
- Narrow angle glaucoma
- Major psychotic disorder
- Severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease
- Subjects on dopamine D2 receptor antagonists, dopamine depleting agents, and metoclopramide.
- Any other medical history determined by investigators to preclude safe participation.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Domino's Farms
Ann Arbor, Michigan, 48105
University Hospital
Ann Arbor, Michigan, 48109
About this study
Official title: Neurobiological Drivers of Mobility Resilience: The Dopaminergic System
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.
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 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)).
- Conditions
- Parkinsonian Signs in Older Persons
- Being tested
- Carbidopa 25 mg, Carbidopa-Levodopa 25/100 mg, Placebo 1, Placebo 2
- Keywords
- slow gait, Parkinsonian signs
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Carbidopa 25 mgDrug
Participants will take one 25mg Carbidopa tablet 3 times a day for 10 days.
Carbidopa-Levodopa 25/100 mgDrug
Also called Sinemet
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 1Drug
Participants will take one 25mg placebo tablet 3 times a day for 10 days.
Placebo 2Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Carbidopa 25 mg; Drug: Carbidopa-Levodopa 25/100 mg |
| 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. Receives: Drug: Placebo 1; Drug: Placebo 2 |
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 and while walking on a sensor mat. Measured in meters per second.
Measured: Baseline and post-intervention (7-13 days after beginning supplement)
Secondary outcomes (3)
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).
Measured: Baseline and post-intervention (7-13 days after beginning supplement)
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.
Measured: 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.
Measured: Baseline and post-intervention (7-13 days after beginning supplement)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2024
- Study start15 Mar 2024
- Primary completion30 May 2024
- Study completion30 May 2024
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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 13 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, Chatkaew Pongmala, University of Michigan
- Investigators
- Chatkaew Pongmala, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06219915
- Sponsor's protocol ID
- HUM00156490-A
- Other IDs
- 5U01AG061393-05
- Acronym
- RES
- Status last verified
- Jun 2025
- First submitted
- 12 Jan 2024
- Last updated
- 17 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2025. 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
- NCT06219915
- Acronym / sponsor ID
- RES / HUM00156490-A
- Conditions
- Parkinsonian Signs in Older Persons
- Keywords
- slow gait, Parkinsonian signs
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 15 Mar 2024 (actual)
- Primary completion
- 30 May 2024 (actual)
- Study completion
- 30 May 2024 (actual)
- First posted
- 23 Jan 2024 (actual)
- Results
- Posted 17 Jun 2025
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 in this double-blinded, placebo-controlled study 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 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)).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Carbidopa Monotherapy and Carbidopa-Levodopa | Experimental | Drug: Carbidopa 25 mg, Drug: Carbidopa-Levodopa 25/100 mgParticipants 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 | Drug: Placebo 1, Drug: Placebo 2Participants 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. |
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 (17 listed)
- Evidence of prior established diagnosis and/or treatment for PD.
- Presence of clinically significant degenerative joint disease and/or neuropathy interfering with proper assessment of the motor exam.
- Presence of significant dementia.
- History of stroke with residual clinical deficit interfering with walking.
- For optional MR imaging only: 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.
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 |
|---|---|---|
| Carbidopa 25 mgParticipants will take one 25mg Carbidopa tablet 3 times a day for 10 days. | Drug | Carbidopa Monotherapy and Carbidopa-Levodopa |
| Carbidopa-Levodopa 25/100 mgAlso: SinemetParticipants 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. | Drug | Carbidopa Monotherapy and Carbidopa-Levodopa |
| Placebo 1Participants will take one 25mg placebo tablet 3 times a day for 10 days. | Drug | Placebo |
| Placebo 2Participants 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. | Drug | Placebo |
Primary outcome
Average Gait Speed
Time frame: Baseline and post-intervention (7-13 days after beginning supplement)
Average gait speed as measured using wearable sensors and while walking on a sensor mat. Measured in meters per second.
3 secondary outcomes
Parkinson's Disease (PD)-Cognitive Rating Scale Score
Time frame: Baseline and post-intervention (7-13 days after beginning supplement)
Mean of Number of Incorrect Responses on the Stroop Color Word Stepping Test
Time frame: Baseline and post-intervention (7-13 days after beginning supplement)
Mean of Reaction Time During the Stroop Color Word Stepping Test
Time frame: Baseline and post-intervention (7-13 days after beginning supplement)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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.
Chatkaew Pongmala, PhD principal investigator
University of Michigan
2 sites 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 25 mg and Carbidopa-Levodopa 25/100 mg in people with Parkinsonian Signs in Older Persons, run by University of Michigan at 2 sites 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 17 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 17 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. 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 17 Jun 2025). 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: Baseline and post-intervention (7-13 days after beginning supplement)). 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 17 Jun 2025.