Parkinson's DiseasePhase 2NCT02206620
Effects of Cholinergic Augmentation on Measures of Balance and Gait
A Phase 2 study testing Donepezil in people with Parkinson's Disease, run by Oregon Health and Science University at 1 site in United States.
Trial summary
This study will compare the effects of placebo and donepezil, a drug that helps conserve concentrations of the neurotransmitter, acetylcholine, on measures of balance and gait in subjects with Parkinson's disease (PD). This study is a double-blind, placebo controlled, cross-over randomized clinical trial. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- Donepezil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2014to Jul 2017
- Phase
- Phase 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 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 30 years old or older
- Diagnosis of idiopathic Parkinson's disease
- Stand unassisted (without use of an assistance device) and walk continuously for at least 2 minutes.
Who cannot join
- musculoskeletal disorders that affect standing and walking
- Uncorrected vision disturbance
- Vestibular problems
- Major depression
- Hallucinations or other psychiatric disturbances
- Tachycardia
Show all 13Show fewer
- Bradycardia
- Arrhythmias
- Peptic ulcer disease
- Use of anticholinergics
- Use of cholinesterase inhibitors
- Use of bladder antispasmodics
- Use of tricyclic antidepressants
Trial locations and contacts
1 site in 1 country.
United States1 site
Oregon Health & Science University
Portland, Oregon, 97239-3098
About this study
This study will compare the effects of placebo and donepezil, a drug that helps conserve concentrations of the neurotransmitter, acetylcholine, on measures of balance and gait in subjects with Parkinson's disease (PD). This study is a double-blind, placebo controlled, cross-over randomized clinical trial. Short-latency afferent inhibition (SAI), a physiological index of cholinergic function will be measured to determine if the deficits in balance and gait correlate with abnormalities of the SAI and if SAI is altered by donepezil as a measure of drug efficacy. Cognitive tests like the Attention Network Test (ANT) will be administered to determine if changes in gait and balance are mediated by changes in attention.
The results of this study will be the most direct test of the hypothesized role of cholinergic neurons and the neurotransmitter, acetylcholine in terms of gait and balance. The study is exploratory because it is not known whether donepezil will affect gait, balance or attention, nor which measures of gait, balance or attention will be sensitive to drug manipulation. The study's immediate goal is to determine the potential utility of cholinergic manipulation as a strategy for preventing or treating balance and gait dysfunction in PD. The findings of this trial are intended to lead to more sharply focused questions about the role of cholinergic neurons in balance and gait and eventually to Phase II B trials to determine clinical utility of cholinergic manipulation to prevent falls and improve mobility.
- Conditions
- Parkinson's Disease
- Being tested
- Donepezil
- 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
| Study group | Role | What they receive |
|---|---|---|
| Donepezil | Experimental | Donepezil 5 mg per day for week 1-3 or 12-14. 10 mg/day for weeks 4-6 or 14-18, if tolerated. Receives: Drug: Donepezil |
| Placebo | Placebo comparator | Placebo 5 mg per day for week 1-3 or 12-14. 10 mg/day for weeks 4-6 or 14-18, if tolerated. Receives: Drug: Donepezil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Delta Medio-lateral Postural Sway Range (Foam)
Increased body sway while standing may be markers for increased risk of falling in Parkinson's disease. Sway was measured with an inertial sensor attached to the waist. Participants did this task on a foam pad. We reported the delta in the donepezil and placebo phases [post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase].
Measured: Six weeks
Delta of the Variability of Stride Time While Walking
Variability in stride time time and an increase with dual tasking is another marker for increased fall risk in Parkinson's disease. Stride time variability was measured with inertial sensors attached to both feet. The delta for each phase is reported [post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase].
Measured: Six weeks
Secondary outcomes (2)
Short-latency Afferent Inhibition is a Marker of Cortical Cholinergic Activity
Short-latency afferent inhibition (SAI) by a peripheral stimulation is a transcranial magnetic stimulation method to evaluate cortical cholinergic activity. Short-latency afferent Inhibition will be used to determine if our subjects with Parkinson's disease have evidence of reduced cholinergic tone which correlates with their measures of postural and gait instability. We report the SAI at the end of each phase (post-placebo phase and post-donepezil phase). SAI is reported in motor-evoked potential (MEP).
Measured: Six weeks
Attention Network Test
Attention Network Test (ANT) is 15 minute computerized test or reaction times with various cues and targets designed to assess alerting, orienting and executive control of attention. Deficits of attention are related to fall risk and may be affected by donepezil.
The delta of the Orienting Network Efficiency is reported for each phase (pre- and post-donepezil phase and pre- and post-placebo phase).
Details: In accordance with Fan et al. (2002), the subtraction method was applied to isolate the efficiency of the three attentional networks as follows: for the alerting network efficiency: mean RT NC trials - mean RT DC trials; for the orienting network efficiency: mean RT CC trials - mean RT SC trials; and for the executive network efficiency: mean RT I trials - mean RT C trials. For both the alerting and orienting effects, higher subtraction scores indicate greater efficiency; by contrast, the more efficient the executive network is, the lower the subtraction score.
Measured: Six weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2014 (estimated)
- Study startJul 2014
- Primary completionJul 2017
- Study completionJul 2017
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Parkinson's 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Collaborators
- Michael J. Fox Foundation for Parkinson's Research
- Responsible party
- Principal investigator, John G. Nutt, Oregon Health and Science University
- Investigators
- John Nutt, M.D., Principal investigator, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02206620
- Sponsor's protocol ID
- 9437
- Status last verified
- Nov 2019
- First submitted
- 29 Jul 2014
- Last updated
- 14 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Mancini M, Fling BW, Gendreau A, Lapidus J, Horak FB, Chung K, Nutt JG. Effect of augmenting cholinergic function on gait and balance. BMC Neurol. 2015 Dec 23;15:264. doi: 10.1186/s12883-015-0523-x.
PubMed 26697847
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Cholinergic Augmentation on Measures of Balance and Gait
- ClinicalTrials.gov ID
- NCT02206620
- Acronym / sponsor ID
- 9437
- Conditions
- Parkinson's Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Collaborators
- Michael J. Fox Foundation for Parkinson's Research
- Study start
- Jul 2014 (actual)
- Primary completion
- Jul 2017 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 1 Aug 2014 (estimated)
- Results
- Posted 14 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will compare the effects of placebo and donepezil, a drug that helps conserve concentrations of the neurotransmitter, acetylcholine, on measures of balance and gait in subjects with Parkinson's disease (PD). This study is a double-blind, placebo controlled, cross-over randomized clinical trial. Short-latency afferent inhibition (SAI), a physiological index of cholinergic function will be measured to determine if the deficits in balance and gait correlate with abnormalities of the SAI and if SAI is altered by donepezil as a measure of drug efficacy. Cognitive tests like the Attention Network Test (ANT) will be administered to determine if changes in gait and balance are mediated by changes in attention.
The results of this study will be the most direct test of the hypothesized role of cholinergic neurons and the neurotransmitter, acetylcholine in terms of gait and balance. The study is exploratory because it is not known whether donepezil will affect gait, balance or attention, nor which measures of gait, balance or attention will be sensitive to drug manipulation. The study's immediate goal is to determine the potential utility of cholinergic manipulation as a strategy for preventing or treating balance and gait dysfunction in PD. The findings of this trial are intended to lead to more sharply focused questions about the role of cholinergic neurons in balance and gait and eventually to Phase II B trials to determine clinical utility of cholinergic manipulation to prevent falls and improve mobility.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Donepezil | Experimental | Drug: DonepezilDonepezil 5 mg per day for week 1-3 or 12-14. 10 mg/day for weeks 4-6 or 14-18, if tolerated. |
| Placebo | Placebo comparator | Drug: DonepezilPlacebo 5 mg per day for week 1-3 or 12-14. 10 mg/day for weeks 4-6 or 14-18, if tolerated. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 30 years old or older
- Diagnosis of idiopathic Parkinson's disease
- Stand unassisted (without use of an assistance device) and walk continuously for at least 2 minutes.
Key exclusion criteria (13 listed)
- musculoskeletal disorders that affect standing and walking
- Uncorrected vision disturbance
- Vestibular problems
- Major depression
- Hallucinations or other psychiatric disturbances
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: Aricept | Drug | Donepezil, Placebo |
Primary outcome
Delta Medio-lateral Postural Sway Range (Foam)
Time frame: Six weeks
Increased body sway while standing may be markers for increased risk of falling in Parkinson's disease. Sway was measured with an inertial sensor attached to the waist. Participants did this task on a foam pad. We reported the delta in the donepezil and placebo phases [post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase].
Delta of the Variability of Stride Time While Walking
Time frame: Six weeks
Variability in stride time time and an increase with dual tasking is another marker for increased fall risk in Parkinson's disease. Stride time variability was measured with inertial sensors attached to both feet. The delta for each phase is reported [post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase].
2 secondary outcomes
Short-latency Afferent Inhibition is a Marker of Cortical Cholinergic Activity
Time frame: Six weeks
Attention Network Test
Time frame: Six weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26697847Mancini M, Fling BW, Gendreau A, Lapidus J, Horak FB, Chung K, Nutt JG. Effect of augmenting cholinergic function on gait and balance. BMC Neurol. 2015 Dec 23;15:264. doi: 10.1186/s12883-015-0523-x.
- The Michael J. Fox Foundation "Fox Trial Finder" Study ListingLink provided by the sponsor.
- 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.
John Nutt, M.D. 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 Phase 2 study testing Donepezil in people with Parkinson's 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 3 inclusion and 13 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 14 Nov 2019. 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?
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 14 Nov 2019). 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?
Delta Medio-lateral Postural Sway Range (Foam) (time frame: Six weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02206620, which also lists 1 linked publication.
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 14 Nov 2019.