Parkinson DiseaseEarly Phase 1NCT03599726
Improving Walking Automaticity in Parkinson's Disease: Levodopa or Donepezil
A Early Phase 1 study testing Donepezil in people with Parkinson Disease, run by Oregon Health and Science University at 1 site in United States.
Trial summary
Safe and independent mobility at home and in the community requires control of walking while accomplishing other functional tasks. A hallmark of healthy control of walking is automaticity, defined as the ability of the nervous system to successfully coordinate movement with minimal use of attention-demanding executive… Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Donepezil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jul 2018to 30 Jul 2019
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must be able to stand unassisted for a minute and to walk continuously for 2 minutes without assistance or assistive devices.
- Diagnosis of idiopathic Parkinson's disease with sensitivity to levodopa and off-medication Hoehn \& Yahr scores of III-IV.
- Subjects must be currently taking levodopa, and not already taking donepezil
- The subjects must be able to appreciate the purpose of the research, give informed consent to participate, be able to cooperate with the testing and be compliant with taking the experimental medications.
Who cannot join
- Other factors affecting gait (hip replacement, musculoskeletal disorder, uncorrected vision or vestibular problem), or an inability to stand or walk for 2 minutes at a time. Major depression, hallucinations or other psychiatric disturbances will be exclusions.
- Medical problems that might be worsened by donepezil are exclusion criteria and include tachycardia, bradycardia, arrhythmias, and peptic ulcer disease.
- Use of anticholinergics for parkinsonism, cholinesterase inhibitors for cognitive problems, bladder antispasmodics for urinary urgency or tricyclic antidepressants for depression are contraindications.
Trial locations and contacts
1 site in 1 country.
United States1 site
Oregon Health & Science University
Portland, Oregon, 97239
About this study
Safe and independent mobility at home and in the community requires control of walking while accomplishing other functional tasks. A hallmark of healthy control of walking is automaticity, defined as the ability of the nervous system to successfully coordinate movement with minimal use of attention-demanding executive resources [1]. Recent evidence indicates that walking disorders are often characterized by a shift in the locomotor control strategy from healthy automaticity to compensatory executive control. This shift is potentially detrimental to walking performance as an executive control strategy is not optimized for locomotor control and it places excessive demands on a limited pool of cognitive reserve.
Here, the investigators hypothesize that walking automaticity, as measured by the prefrontal cortex activity while walking, will be improved by donepezil (a cholinesterase inhibitor).
Read the detailed description
A challenge to studying automaticity is that central nervous system circuitry for locomotion cannot be directly assessed in humans so shifts between automaticity and executive control have been inferred with a dual-task paradigm. If gait slows or deteriorates during a concurrent cognitive task, gait is deemed less automatic and using more cortical control. Recently, a more direct measure of automaticity has been studied with functional near infrared spectroscopy (fNIRS). fNIRS is used to measure changes in cortical oxygenated hemoglobin (HbO2) levels using light-tissue interaction properties of light within the near infrared range, similar to the way the HbO2 is detected with magnetic resonance imaging. Increased oxygenated hemoglobin are related to increased blood flow, which, in turn, reflects increased cortical activity.
A recent study shows higher than normal activation of the prefrontal cortex during usual walking in patients with PD, an indicator of increased cortical control and reduced automaticity. An enhanced understanding of the neurochemistry underlying gait automaticity in PD will have implications for pharmacologic management of gait impairment in PD. If reduced gait automaticity is due to depressed central dopamine, then more aggressive dopaminergic strategies may be in order. On the other hand, if reduced gait automaticity is due to depressed central cholinergic tone (as the investigators hypothesize), then cholinergic strategies will be more effective for optimizing gait in PD. Few studies have explored the positive effects of cholinergic augmentation on gait and falls but none have examined its direct effects on gait automaticity.
Aim I. Examine the effect of donepezil or levodopa on walking automaticity, as measured by prefrontal cortex activity while walking. This study will employ a double-blind, two-way crossover design in which 20 participants with idiopathic PD will be tested either after 14 days of placebo and their regular dose of levodopa or after 14 days of donepezil (5 mg/day oral) and their regular dose of levodopa. Levodopa doses are not determined or controlled by the investigators, as the recruited participants are already on levodopa specific to their own needs. The investigators will measure automaticity by measuring the activity of the prefrontal cortex while walking in single- and dual-task conditions with a wireless fNIRS system. The investigators predict that donepezil plus levodopa will decrease the prefrontal cortex activity, indicating more automaticity, during walking compared to placebo and levodopa.
Aim II. Relate walking automaticity with spatio-temporal measures of walking. In addition to walking automaticity measured with fNIRS while walking, subjects will be equipped with 3 inertial sensors to measure spatio-temporal features of gait, such as stride time, stride length and their variability. The investigators hypothesize that variability of gait will be related to level of prefrontal cortex activity. The investigators predict that variability of gait will not change with levodopa, reflecting prefrontal control of walking. In contrast, the investigators predict that donepezil will improve variability of gait, both with and without a concurrent, cognitive task.
- Conditions
- Parkinson Disease
- Being tested
- Donepezil, Placebo
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DonepezilDrug
Also called Aricept
Donepezil 5 mg per day for week 1-2 or 5-6
PlaceboDrug
Placebo 5 mg per day for week 1-2 or 5-6
| Study group | Role | What they receive |
|---|---|---|
| Active study drug: Donepezil | Experimental | Donepezil 5 mg per day for week 1-2 or 5-6 Receives: Drug: Donepezil |
| Placebo study drug: Placebo | Placebo comparator | Placebo 5 mg per day for week 1-2 or 5-6 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oxygenated Hemoglobin levels in the prefrontal cortex while walking (microM).
Oxygenated hemoglobin changes during walking, compared to standing, will be quantified with a wireless functional near infrared spectroscopy (fNIRS). Subjects with PD will be tested while walking after 14 days of placebo and their regular dose of levodopa or after 14 days of donepezil (5 mg/day oral) and their regular dose of levodopa, with a two week wash out in between.
Measured: 43 days
Secondary outcomes (5)
Stride time variability of gait (%).
Subjects will be equipped with 3 inertial sensors during walking and turning tasks to measure spatio-temporal features of gait and turning features. The walking will be 2 min long in duration over a path of 9 feet. Stride time variability will be calculated as: mean(stride time)/SD (stride time)*100 of all the gait cycles detected for walking.
Measured: 43 days
Gait speed (m/s)
Average gait speed during the walking tasks.
Measured: 43 days
Stride length (m)
Average stride length calculated as the mean of all the detected gait cycles.
Measured: 43 days
Turning velocity (degrees/s)
Turning will be identified from the yaw angular velocity of the sensor on the waist. Turning velocity is calculated as the peak of the angular velocity during turning.
Measured: 43 days
Turning duration (s)
Turning will be identified from the yaw angular velocity of the sensor on the waist. Turning duration represents the duration of the turn while walking.
Measured: 43 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2018
- Study start30 Jul 2018
- Primary completion30 May 2019
- Study completion30 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by Oregon Health and Science UniversityThe 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Foundation, Oregon
- Responsible party
- Principal investigator, Martina Mancini, Oregon Health and Science University
- Investigators
- Martina Mancini, PhD, Principal investigator, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03599726
- Sponsor's protocol ID
- eIRB 17805
- Status last verified
- May 2020
- First submitted
- 29 Jun 2018
- Last updated
- 11 May 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Walking Automaticity in Parkinson's Disease: Levodopa or Donepezil
- ClinicalTrials.gov ID
- NCT03599726
- Acronym / sponsor ID
- eIRB 17805
- Conditions
- Parkinson Disease
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Collaborators
- Medical Research Foundation, Oregon
- Study start
- 30 Jul 2018 (actual)
- Primary completion
- 30 May 2019 (actual)
- Study completion
- 30 Jul 2019 (actual)
- First posted
- 26 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Safe and independent mobility at home and in the community requires control of walking while accomplishing other functional tasks. A hallmark of healthy control of walking is automaticity, defined as the ability of the nervous system to successfully coordinate movement with minimal use of attention-demanding executive resources [1]. Recent evidence indicates that walking disorders are often characterized by a shift in the locomotor control strategy from healthy automaticity to compensatory executive control. This shift is potentially detrimental to walking performance as an executive control strategy is not optimized for locomotor control and it places excessive demands on a limited pool of cognitive reserve.
Here, the investigators hypothesize that walking automaticity, as measured by the prefrontal cortex activity while walking, will be improved by donepezil (a cholinesterase inhibitor).
Detailed description
A challenge to studying automaticity is that central nervous system circuitry for locomotion cannot be directly assessed in humans so shifts between automaticity and executive control have been inferred with a dual-task paradigm. If gait slows or deteriorates during a concurrent cognitive task, gait is deemed less automatic and using more cortical control. Recently, a more direct measure of automaticity has been studied with functional near infrared spectroscopy (fNIRS). fNIRS is used to measure changes in cortical oxygenated hemoglobin (HbO2) levels using light-tissue interaction properties of light within the near infrared range, similar to the way the HbO2 is detected with magnetic resonance imaging. Increased oxygenated hemoglobin are related to increased blood flow, which, in turn, reflects increased cortical activity.
A recent study shows higher than normal activation of the prefrontal cortex during usual walking in patients with PD, an indicator of increased cortical control and reduced automaticity. An enhanced understanding of the neurochemistry underlying gait automaticity in PD will have implications for pharmacologic management of gait impairment in PD. If reduced gait automaticity is due to depressed central dopamine, then more aggressive dopaminergic strategies may be in order. On the other hand, if reduced gait automaticity is due to depressed central cholinergic tone (as the investigators hypothesize), then cholinergic strategies will be more effective for optimizing gait in PD. Few studies have explored the positive effects of cholinergic augmentation on gait and falls but none have examined its direct effects on gait automaticity.
Aim I. Examine the effect of donepezil or levodopa on walking automaticity, as measured by prefrontal cortex activity while walking. This study will employ a double-blind, two-way crossover design in which 20 participants with idiopathic PD will be tested either after 14 days of placebo and their regular dose of levodopa or after 14 days of donepezil (5 mg/day oral) and their regular dose of levodopa. Levodopa doses are not determined or controlled by the investigators, as the recruited participants are already on levodopa specific to their own needs. The investigators will measure automaticity by measuring the activity of the prefrontal cortex while walking in single- and dual-task conditions with a wireless fNIRS system. The investigators predict that donepezil plus levodopa will decrease the prefrontal cortex activity, indicating more automaticity, during walking compared to placebo and levodopa.
Aim II. Relate walking automaticity with spatio-temporal measures of walking. In addition to walking automaticity measured with fNIRS while walking, subjects will be equipped with 3 inertial sensors to measure spatio-temporal features of gait, such as stride time, stride length and their variability. The investigators hypothesize that variability of gait will be related to level of prefrontal cortex activity. The investigators predict that variability of gait will not change with levodopa, reflecting prefrontal control of walking. In contrast, the investigators predict that donepezil will improve variability of gait, both with and without a concurrent, cognitive task.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active study drug: Donepezil | Experimental | Drug: DonepezilDonepezil 5 mg per day for week 1-2 or 5-6 |
| Placebo study drug: Placebo | Placebo comparator | Drug: PlaceboPlacebo 5 mg per day for week 1-2 or 5-6 |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Subjects must be able to stand unassisted for a minute and to walk continuously for 2 minutes without assistance or assistive devices.
- Diagnosis of idiopathic Parkinson's disease with sensitivity to levodopa and off-medication Hoehn \& Yahr scores of III-IV.
- Subjects must be currently taking levodopa, and not already taking donepezil
- The subjects must be able to appreciate the purpose of the research, give informed consent to participate, be able to cooperate with the testing and be compliant with taking the experimental medications.
Key exclusion criteria (3 listed)
- Other factors affecting gait (hip replacement, musculoskeletal disorder, uncorrected vision or vestibular problem), or an inability to stand or walk for 2 minutes at a time. Major depression, hallucinations or other psychiatric disturbances will be exclusions.
- Medical problems that might be worsened by donepezil are exclusion criteria and include tachycardia, bradycardia, arrhythmias, and peptic ulcer disease.
- Use of anticholinergics for parkinsonism, cholinesterase inhibitors for cognitive problems, bladder antispasmodics for urinary urgency or tricyclic antidepressants for depression are contraindications.
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 |
|---|---|---|
| DonepezilAlso: AriceptDonepezil 5 mg per day for week 1-2 or 5-6 | Drug | Active study drug: Donepezil |
| PlaceboPlacebo 5 mg per day for week 1-2 or 5-6 | Drug | Placebo study drug: Placebo |
Primary outcome
Oxygenated Hemoglobin levels in the prefrontal cortex while walking (microM).
Time frame: 43 days
Oxygenated hemoglobin changes during walking, compared to standing, will be quantified with a wireless functional near infrared spectroscopy (fNIRS). Subjects with PD will be tested while walking after 14 days of placebo and their regular dose of levodopa or after 14 days of donepezil (5 mg/day oral) and their regular dose of levodopa, with a two week wash out in between.
5 secondary outcomes
Stride time variability of gait (%).
Time frame: 43 days
Gait speed (m/s)
Time frame: 43 days
Stride length (m)
Time frame: 43 days
Turning velocity (degrees/s)
Time frame: 43 days
Turning duration (s)
Time frame: 43 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2020.
- Individual participant dataSharing planned: Undecided
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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.
Martina Mancini, PhD principal investigator
Oregon Health and Science University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Donepezil in people with Parkinson Disease, run by Oregon Health and Science University 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 4 inclusion and 3 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 11 May 2020. 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. 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 phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Oxygenated Hemoglobin levels in the prefrontal cortex while walking (microM). (time frame: 43 days). 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 11 May 2020.