Parkinson's DiseasePhase 2UdallP3NCT02933372
Cholinergic Mechanisms of Gait Dysfunction in Parkinson's Disease Experiments 1 & 2 - Proj #3
A Phase 2 study testing Varenicline in people with Parkinson's Disease, run by University of Michigan.
Trial summary
Varying oral doses of Varenicline (VCN), starting with very low doses, will be administered to participants with Parkinson's Disease (PD) or healthy controls without PD for several days. Read more about this study
- Who is it for?
- Ages 45 years and olderHealthy volunteers can take part
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- Varenicline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- No sites listed yet
- Study dates
- 5 Oct 2015to 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
- Healthy volunteers accepted
- 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.
About this study
Official title: Cholinergic Mechanisms of Gait Dysfunction in Parkinson's Disease Experiments 1 & 2 - Projects #3
Varying oral doses of Varenicline (VCN), starting with very low doses, will be administered to participants with Parkinson's Disease (PD) or healthy controls without PD for several days. Positron emission tomography (PET) scans after administration of VCN will be used to determine the lowest oral dose of VCN producing an adequate brain level of VCN. These experiments (1 \& 2) will be used to determine an appropriate oral dose of VCN to administer to PD participants for experiment 3 of the study (see NCT04403399).
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
- 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
Participants take varenicline for 10 days. Each participant will be on one dosage throughout the 10 days, but not all participants receive the same dosage. The dosages that were utilized for both Parkinson's disease participants and healthy volunteers were 0.25mg once a day, 0.25mg twice a day, and 0.5mg twice a day. A fourth dosing group of 1 mg varenicline twice a day was studied in Parkinson's disease participants, but not in healthy volunteers.
| Study group | Role | What they receive |
|---|---|---|
| Parkinson's Disease Patients | Experimental | Participants take varenicline for several days and have two Positron Emission Tomography (PET) scans. PET scans are used to estimate how much varenicline is actually in the brain. Safety monitoring with clinical assessments of severity of Parkinson disease (PD) and cognition are performed. Receives: Drug: Varenicline |
| Healthy Controls | Experimental | Participants take varenicline for several days and have two Positron Emission Tomography (PET) scans. The PET scans are used to estimate how much varenicline is actually in the brain. Safety monitoring with clinical assessments for presence of Parkinson disease (PD) and cognition are performed. Receives: Drug: Varenicline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Varenicline Occupancy of alpha4beta2* Nicotinic Acetylcholine Receptors
Varenicline occupancy of alpha4beta2* nicotinic acetylcholine receptors (nAChR) was assessed with ascending doses of varenicline and the selective alpha4beta2* nAChR positron emission tomography (PET) ligand [18F]Flubatine. Alpha4beta2* nAChR agonists may induce nAChR expression. Consequently, we imaged participants at the end of their drug exposure periods (Day 10) and again after 5 days (~5 half-lives) of washout from drug exposure (Day 15). We used the difference between the two PET scans, (Day 10 - Day 15)/Day 15 x 100%, to determine the receptor occupancy of alpha4beta2* nicotinic acetylcholine receptors (nAChR) by each dose of varenicline.
Measured: 15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2016 (estimated)
- Study start5 Oct 2015
- 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.
- 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
- Parallel groups
- Model description
- All participants (Parkinson's disease patients and healthy controls) will receive the study drug varenicline.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 25 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
- NCT02933372
- Sponsor's protocol ID
- HUM00093188
- Acronym
- UdallP3
- Status last verified
- Jan 2021
- First submitted
- 6 Apr 2016
- Last updated
- 12 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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 12 Feb 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 Experiments 1 & 2 - Projects #3
- ClinicalTrials.gov ID
- NCT02933372
- Acronym / sponsor ID
- UdallP3 / HUM00093188
- Conditions
- Parkinson's Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Study start
- 5 Oct 2015 (actual)
- Primary completion
- 26 Jun 2019 (actual)
- Study completion
- 26 Jun 2019 (actual)
- First posted
- 14 Oct 2016 (estimated)
- Results
- Posted 12 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Varying oral doses of Varenicline (VCN), starting with very low doses, will be administered to participants with Parkinson's Disease (PD) or healthy controls without PD for several days. Positron emission tomography (PET) scans after administration of VCN will be used to determine the lowest oral dose of VCN producing an adequate brain level of VCN. These experiments (1 \& 2) will be used to determine an appropriate oral dose of VCN to administer to PD participants for experiment 3 of the study (see NCT04403399).
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
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- All participants (Parkinson's disease patients and healthy controls) will receive the study drug varenicline.
| Arm | Type | Receives |
|---|---|---|
| Parkinson's Disease Patients | Experimental | Drug: VareniclineParticipants take varenicline for several days and have two Positron Emission Tomography (PET) scans. PET scans are used to estimate how much varenicline is actually in the brain. Safety monitoring with clinical assessments of severity of Parkinson disease (PD) and cognition are performed. |
| Healthy Controls | Experimental | Drug: VareniclineParticipants take varenicline for several days and have two Positron Emission Tomography (PET) scans. The PET scans are used to estimate how much varenicline is actually in the brain. Safety monitoring with clinical assessments for presence of Parkinson disease (PD) and cognition are performed. |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- 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: ChantixParticipants take varenicline for 10 days. Each participant will be on one dosage throughout the 10 days, but not all participants receive the same dosage. The dosages that were utilized for both Parkinson's disease participants and healthy volunteers were 0.25mg once a day, 0.25mg twice a day, and 0.5mg twice a day. A fourth dosing group of 1 mg varenicline twice a day was studied in Parkinson's disease participants, but not in healthy volunteers. | Drug | Healthy Controls, Parkinson's Disease Patients |
Primary outcome
Varenicline Occupancy of alpha4beta2* Nicotinic Acetylcholine Receptors
Time frame: 15 days
Varenicline occupancy of alpha4beta2* nicotinic acetylcholine receptors (nAChR) was assessed with ascending doses of varenicline and the selective alpha4beta2* nAChR positron emission tomography (PET) ligand [18F]Flubatine. Alpha4beta2* nAChR agonists may induce nAChR expression. Consequently, we imaged participants at the end of their drug exposure periods (Day 10) and again after 5 days (~5 half-lives) of washout from drug exposure (Day 15). We used the difference between the two PET scans, (Day 10 - Day 15)/Day 15 x 100%, to determine the receptor occupancy of alpha4beta2* nicotinic acetylcholine receptors (nAChR) by each dose of varenicline.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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
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.
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 12 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
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 12 Feb 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?
Varenicline Occupancy of alpha4beta2* Nicotinic Acetylcholine Receptors (time frame: 15 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 12 Feb 2021.