Parkinson's DiseasePhase 2UdallP3E3NCT04403399
Crossover Target Engagement Study of Cholinergic Mechanisms of Gait Dysfunction in Parkinson's Disease (Project #3 - Experiment 3 [UdallP3E3])
A Phase 2 study testing Varenicline in people with Parkinson's Disease, run by University of Michigan at 1 site in United States.
Trial summary
With an appropriate oral dose of Varenicline (VCN) identified from experiments 1 \& 2 of the study (see NCT02933372), the investigators will administer VCN to Parkinson Disease (PD) participants to determine if VCN improves walking speed and measures of balance. Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- Varenicline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Jun 2017to 26 Jun 2019
- 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 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PD diagnosis will be based on the United Kingdom Parkinson's Disease Society Brain Bank Research Center (UKPDSBRC) clinical diagnostic criteria. The investigators will enrich the cohort by recruiting subjects at modified Hoehn and Yahr stages 2 or higher, duration of motor disease 5 years or longer, age >65 years, or the Postural Instability and Gait Disorder (PIGD) phenotype. Duration of motor disease will be defined as the time between onset of motor symptoms and time of entry into the study. The PIGD phenotype is defined as described previously. PD subjects with defined cholinergic deficits will be recruited as described in Project II. PD subjects will have cortical cholinergic deficits based on 5th percentile cutoff of the normal controls as defined previously.
- Stable dopaminergic replacement therapy for 3 months prior to enrollment and expected to maintain stable dopaminergic therapy for duration of study participation.
Who cannot join
- Other disorders which may resemble PD with or without dementia, such as vascular dementia, normal pressure hydrocephalus, progressive supranuclear palsy, multiple system atrophy, corticobasal ganglionic degeneration, or toxic causes of parkinsonism. Prototypical cases have distinctive clinical profiles, like vertical supranuclear gaze palsy, early and severe dysautonomia or appendicular apraxia, which may differentiate them from idiopathic PD. The use of the UKPDSBRC clinical diagnostic criteria for PD will mitigate the inclusion of subjects with atypical parkinsonism and all participants will undergo [11-Carbon]dihydrotetrabenazine PET to confirm striatal dopaminergic denervation.
- Subjects on neuroleptic, anticholinergic (trihexphenidyl, benztropine), or cholinesterase inhibitor drugs.
- Current or previous (within last 6 months) use of any product or medication containing nicotinic agents,including use of tobacco products such as cigarettes, cigars, pipes, chewing tobacco, etc., electronic cigarettes, over-the-counter nicotine patches, chewing gum containing nicotine, or varenicline.
- Evidence of a stroke 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 MR or PET imaging
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- Subjects limited by participation in research procedures involving ionizing radiation.
- Pregnancy (test within 48 hours of each PET session) or breastfeeding.
- Significant risk of cardiovascular event.
- Active, significant mood disorder.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Cholinergic Mechanisms of Gait Dysfunction in Parkinson's Disease Experiment 3 - Project #3
With an appropriate oral dose of Varenicline (VCN) identified from experiments 1 \& 2 of the study (see NCT02933372), the investigators will administer VCN to Parkinson Disease (PD) participants to determine if VCN improves walking speed and measures of balance. PD participants will receive VCN or a placebo (fake drug) for 3 weeks to assess the effects of VCN administration on gait speed and balance. Participants will undergo examinations to assess the intensity of their Parkinsonism and asked questions to assess their mood and thinking.
Read the detailed description
To demonstrate that α4β2* nAChRs are appropriate therapeutic targets in Parkinson's Disease (PD), it is necessary to study key pharmacokinetic-pharmacodynamic features of α4β2* nAChR in the context of the PD brain with loss of nerve cells that produce the neurotransmitter acetylcholine, a pathologic environment in which they may exhibit unique features. This personalized medicine approach focuses our studies on the subgroup of PD subjects with loss of nerve cells that produce the neurotransmitter acetylcholine identified by Project II and the Clinical Resource Core. The investigators will assess α4β2* nAChR features using PET imaging with the α4β2* nAChR ligand [18-Fluorine]flubatine, subacute administration of the α4β2* nAChR partial agonist Varenicline (VCN), and laboratory measures of gait, balance, and attention. The investigators will use [18-Fluorine] flubatine PET to assess VCN occupancy of brain α4β2* nAChRs (experiments 1 \& 2). VCN will be administered to both PD participants (experiment 1) and healthy controls (experiment 2) and both populations will undergo a flubatine PET scan to assess VCN occupancy. Using this PET data to select an appropriate VCN dose, the investigators will perform a pharmacodynamic study (experiment 3) with subacute VCN administration to determine if α4β2* nAChR stimulation improves laboratory measures of gait function, postural control, and attentional function in PD subjects with loss of nerve cells that produce the neurotransmitter acetylcholine.
- Conditions
- Parkinson's Disease
- Being tested
- Varenicline, 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.
VareniclineDrug
Also called Chantix
Initial 0.25 mg oral dose of varenicline administered with monitoring over 4 hours, then total daily dose escalated over the next 2 days until final 0.5 mg BID oral varenicline administered for the remaining 3 weeks.
PlaceboDrug
Initial placebo oral dose administered with monitoring over 4 hours, then total daily dose escalated over the next 2 days until final placebo BID dosing administered orally for the remaining 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Varenicline then Placebo | Experimental | Varenicline 0.5 mg BID orally for 3 weeks, followed by a 3-week washout period, then placebo BID orally for 3 weeks Receives: Drug: Varenicline; Drug: Placebo |
| Placebo then Varenicline | Experimental | Placebo BID orally for 3 weeks, followed by a 3-week washout period, then Varenicline 0.5 mg BID orally for 3 weeks Receives: Drug: Varenicline; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gait Speed
Gait speed, how fast a person can walk down a corridor, at normal pace with no distractors (i.e., no dual task).
Measured: end of each period: 22 and 64 days
JERK
JERK is the time based derivative of spontaneous lower trunk accelerations during standing. It was assessed with the Ambulatory Parkinson's Disease Monitoring (APDM) wearable sensor system (APDM Wearable Technologies, Inc.) using the iSWAY protocol, with participants standing on a foam pad with eyes closed. JERK was calculated using the manufacturer's software (Mobility Lab Version 1).
Measured: end of each period: 22 and 64 days
Secondary outcomes (1)
Attention
Attention function will be measured with a standard computer test, the Sustained Attention Test (SAT), without a distractor condition. Results are reported as the vigilance index, a measure that corrects estimates of accurate detection with penalties for false detection and not confounded by errors of omission. (Frey PW, Colliver JA. Sensitivity and responsivity measures for discrimination learning. Learn Motiv 1973; 4:327-342.) The minimum score is -1.00 (indicating that all recorded responses were misses or false alarms) and maximum is +1 (indicating that all recorded responses were hits or correct rejections). Higher values indicate better attentional performance.
Measured: end of period: days 22 and 64
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2020
- Study start29 Jun 2017
- Primary completion26 Jun 2019
- Study completion26 Jun 2019
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 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Roger L. Albin, University of Michigan
- Investigators
- Roger L Albin, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04403399
- Sponsor's protocol ID
- HUM00093188-a
- Acronym
- UdallP3E3
- Status last verified
- Jan 2021
- First submitted
- 21 May 2020
- Last updated
- 27 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mancini M, Carlson-Kuhta P, Zampieri C, Nutt JG, Chiari L, Horak FB. Postural sway as a marker of progression in Parkinson's disease: a pilot longitudinal study. Gait Posture. 2012 Jul;36(3):471-6. doi: 10.1016/j.gaitpost.2012.04.010. Epub 2012 Jun 29.
PubMed 22750016
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cholinergic Mechanisms of Gait Dysfunction in Parkinson's Disease Experiment 3 - Project #3
- ClinicalTrials.gov ID
- NCT04403399
- Acronym / sponsor ID
- UdallP3E3 / HUM00093188-a
- Conditions
- Parkinson's Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Study start
- 29 Jun 2017 (actual)
- Primary completion
- 26 Jun 2019 (actual)
- Study completion
- 26 Jun 2019 (actual)
- First posted
- 27 May 2020 (actual)
- Results
- Posted 27 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
With an appropriate oral dose of Varenicline (VCN) identified from experiments 1 \& 2 of the study (see NCT02933372), the investigators will administer VCN to Parkinson Disease (PD) participants to determine if VCN improves walking speed and measures of balance. PD participants will receive VCN or a placebo (fake drug) for 3 weeks to assess the effects of VCN administration on gait speed and balance. Participants will undergo examinations to assess the intensity of their Parkinsonism and asked questions to assess their mood and thinking.
Detailed description
To demonstrate that α4β2* nAChRs are appropriate therapeutic targets in Parkinson's Disease (PD), it is necessary to study key pharmacokinetic-pharmacodynamic features of α4β2* nAChR in the context of the PD brain with loss of nerve cells that produce the neurotransmitter acetylcholine, a pathologic environment in which they may exhibit unique features. This personalized medicine approach focuses our studies on the subgroup of PD subjects with loss of nerve cells that produce the neurotransmitter acetylcholine identified by Project II and the Clinical Resource Core. The investigators will assess α4β2* nAChR features using PET imaging with the α4β2* nAChR ligand [18-Fluorine]flubatine, subacute administration of the α4β2* nAChR partial agonist Varenicline (VCN), and laboratory measures of gait, balance, and attention. The investigators will use [18-Fluorine] flubatine PET to assess VCN occupancy of brain α4β2* nAChRs (experiments 1 \& 2). VCN will be administered to both PD participants (experiment 1) and healthy controls (experiment 2) and both populations will undergo a flubatine PET scan to assess VCN occupancy. Using this PET data to select an appropriate VCN dose, the investigators will perform a pharmacodynamic study (experiment 3) with subacute VCN administration to determine if α4β2* nAChR stimulation improves laboratory measures of gait function, postural control, and attentional function in PD subjects with loss of nerve cells that produce the neurotransmitter acetylcholine.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Varenicline then Placebo | Experimental | Drug: Varenicline, Drug: PlaceboVarenicline 0.5 mg BID orally for 3 weeks, followed by a 3-week washout period, then placebo BID orally for 3 weeks |
| Placebo then Varenicline | Experimental | Drug: Varenicline, Drug: PlaceboPlacebo BID orally for 3 weeks, followed by a 3-week washout period, then Varenicline 0.5 mg BID orally for 3 weeks |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- PD diagnosis will be based on the United Kingdom Parkinson's Disease Society Brain Bank Research Center (UKPDSBRC) clinical diagnostic criteria. The investigators will enrich the cohort by recruiting subjects at modified Hoehn and Yahr stages 2 or higher, duration of motor disease 5 years or longer, age >65 years, or the Postural Instability and Gait Disorder (PIGD) phenotype. Duration of motor disease will be defined as the time between onset of motor symptoms and time of entry into the study. The PIGD phenotype is defined as described previously. PD subjects with defined cholinergic deficits will be recruited as described in Project II. PD subjects will have cortical cholinergic deficits based on 5th percentile cutoff of the normal controls as defined previously.
- Stable dopaminergic replacement therapy for 3 months prior to enrollment and expected to maintain stable dopaminergic therapy for duration of study participation.
Key exclusion criteria (10 listed)
- Other disorders which may resemble PD with or without dementia, such as vascular dementia, normal pressure hydrocephalus, progressive supranuclear palsy, multiple system atrophy, corticobasal ganglionic degeneration, or toxic causes of parkinsonism. Prototypical cases have distinctive clinical profiles, like vertical supranuclear gaze palsy, early and severe dysautonomia or appendicular apraxia, which may differentiate them from idiopathic PD. The use of the UKPDSBRC clinical diagnostic criteria for PD will mitigate the inclusion of subjects with atypical parkinsonism and all participants will undergo [11-Carbon]dihydrotetrabenazine PET to confirm striatal dopaminergic denervation.
- Subjects on neuroleptic, anticholinergic (trihexphenidyl, benztropine), or cholinesterase inhibitor drugs.
- Current or previous (within last 6 months) use of any product or medication containing nicotinic agents,including use of tobacco products such as cigarettes, cigars, pipes, chewing tobacco, etc., electronic cigarettes, over-the-counter nicotine patches, chewing gum containing nicotine, or varenicline.
- Evidence of a stroke 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.
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 |
|---|---|---|
| VareniclineAlso: ChantixInitial 0.25 mg oral dose of varenicline administered with monitoring over 4 hours, then total daily dose escalated over the next 2 days until final 0.5 mg BID oral varenicline administered for the remaining 3 weeks. | Drug | Placebo then Varenicline, Varenicline then Placebo |
| PlaceboInitial placebo oral dose administered with monitoring over 4 hours, then total daily dose escalated over the next 2 days until final placebo BID dosing administered orally for the remaining 3 weeks. | Drug | Placebo then Varenicline, Varenicline then Placebo |
Primary outcome
Gait Speed
Time frame: end of each period: 22 and 64 days
Gait speed, how fast a person can walk down a corridor, at normal pace with no distractors (i.e., no dual task).
JERK
Time frame: end of each period: 22 and 64 days
JERK is the time based derivative of spontaneous lower trunk accelerations during standing. It was assessed with the Ambulatory Parkinson's Disease Monitoring (APDM) wearable sensor system (APDM Wearable Technologies, Inc.) using the iSWAY protocol, with participants standing on a foam pad with eyes closed. JERK was calculated using the manufacturer's software (Mobility Lab Version 1).
1 secondary outcome
Attention
Time frame: end of period: days 22 and 64
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22750016Mancini M, Carlson-Kuhta P, Zampieri C, Nutt JG, Chiari L, Horak FB. Postural sway as a marker of progression in Parkinson's disease: a pilot longitudinal study. Gait Posture. 2012 Jul;36(3):471-6. doi: 10.1016/j.gaitpost.2012.04.010. Epub 2012 Jun 29.
- Individual participant dataSharing planned: No
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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.
Roger L Albin, 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 2 study testing Varenicline in people with Parkinson's Disease, 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 10 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 27 Jan 2021. 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 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 27 Jan 2021). 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?
Gait Speed (time frame: end of each period: 22 and 64 days). 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 NCT04403399, 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 27 Jan 2021.