Parkinson's DiseaseFOGNCT03647137
Amyloidopathy, Cholinopathy, Dopamine Responsiveness and Freezing of Gait in PD
An observational study of Parkinson's Disease, run by VA Office of Research and Development at 1 site in United States.
Trial summary
Early stage Parkinson disease (PD) is characterized by a 'honeymoon' phase in terms of responsiveness of motor symptoms, including gait, to dopaminergic pharmacotherapy. Advancing PD is associated with disabling axial motor complications, such as freezing of gait (FoG), with decreased or even refractory dopamine… Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- Detailed motor testing, including FoG, in PD subjects
- How many people
- 53 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Jun 2016to 26 May 2021
- Phase
- Observational
- 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Community sample recruited from the following sources 1. UMHS Movement Disorders Clinics 2. VA Ann Arbor HS Movement Disorders Clinic 3. Existing studies at Functional Neuroimaging, Cognitive, and Mobility Lab at the University of Michigan
Who may be able to join
- PD based on the United Kingdom Parkinson's Disease Society Brain Bank
- Diagnostic Research Criteria with or without Freezing of Gait
- Duration of Disease > 5 years
- Mini-Mental State Examination (MMSE) > 23
Who cannot join
- Dementia
- Dementia with Lewy Bodies
- Other disorders which may resemble PD
- Subjects on neuroleptic, anticholinergic (trihexyphenidyl, benztropine) or cholinesterase inhibitor drugs
- Evidence of a stroke or mass lesion on structural brain imaging (MRI)
- Participants in whom MRI is contraindicated including, but not limited to:
Show all 12Show fewer
- those with a pacemaker
- presence of metallic fragments near the eyes or spinal cord
- cochlear implant
- Severe claustrophobia precluding MR or PET imaging
- Subjects limited by participation in research procedures involving ionizing radiation
- Pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Ann Arbor Healthcare System, Ann Arbor, MI
Ann Arbor, Michigan, 48105
About this study
Early stage Parkinson disease (PD) is characterized by a 'honeymoon' phase in terms of responsiveness of motor symptoms, including gait, to dopaminergic pharmacotherapy. Advancing PD is associated with disabling axial motor complications, such as freezing of gait (FoG), with decreased or even refractory dopamine responsiveness in over 50% of patients. The management of dopamine resistant gait problems represents the most important unmet need in PD. This study will related detailed motor testing to brain PET imaging to see if certain molecules (or lack thereof) involved with neurologic transmission in the brain are involved with FoG.
Read the detailed description
Early stage Parkinson disease (PD) is characterized by a 'honeymoon' phase in terms of responsiveness of motor symptoms, including gait, to dopaminergic pharmacotherapy. Advancing PD is associated with disabling axial motor complications, such as freezing of gait (FoG), with decreased or even refractory dopamine responsiveness in over 50% of patients. The management of dopamine resistant gait problems represents the most important unmet need in PD. At present, there is no biomarker of FoG in patients with PD as there is a lack of mechanistic understanding of dopamine nonresponsiveness of FoG. The investigators have previously identified cholinergic denervation as a prominent factor related to both falls and gait slowing in PD. The investigators recently identified that cortical -amyloid deposition not only associates with cognitive decline but also with postural instability and gait difficulties in PD. In this proposal, the investigators present preliminary data suggesting that FoG is associated with either cholinopathy, amyloidopathy or both in PD. The investigators propose to test the novel hypothesis that comorbid amyloidopathy may be a possible mechanistic factor underlying the poor response of FoG to dopaminergic therapy in advancing PD. In contrast, isolated cholinopathy would be expected to be associated with preserved dopamine responsiveness of FoG. For this purpose, the investigators propose to perform detailed motor, including FoG, testing in PD patients "on" and "off" their dopaminergic medications and relate this to dopaminergic 11C-dihydrotetrabenazine (DTBZ), vesicular acetylcholine transporter 18F-fluoroethoxybenzovesamicol (FEOBV) and -amyloid 11C-labeled Pittsburgh Compound-B (PIB) brain PET imaging in PD subjects with and without FoG. Furthermore, based on recent clinical observations that serotoninergic drugs, like the popular anti-depressant selective serotonin reuptake inhibitor (SSRI) drugs, are associated with significantly lower build- up of -amyloid plaques in the elderly population, and based on the investigators' subsequent observation of an intriguing inverse relationship between -amyloid plaque deposition and striatal serotoninergic terminal in PD, the investigators propose to perform an exploratory sub-study to test a new hypothesis that PD subjects with FoG will exhibit not only higher striatal -amyloid but also lower striatal serotoninergic innervation (as determined by 11C-DASB serotonin PET imaging) compared to PD subjects without FoG. If confirmed, positive findings in this study would allow the identification of different PD subgroups ('personalized medicine'), such as presence amyloidopathy or cholinopathy, to select patients for targeted pharmacotherapies to potentially prevent the development of FoG (anti-amyloid, such as serotoninergic drugs) or manage its clinical manifestation (cholinergic augmentation therapy) in order to preserve and maintain a good quality of life in individuals with PD.
- Conditions
- Parkinson's Disease
- Being tested
- Detailed motor testing, including FoG, in PD subjects
- Keywords
- freezing of gait, amyloid, cholinergic, mobility, PET, imaging, MRI
- Medical subject headings
- Parkinson Disease, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Detailed motor testing, including FoG, in PD subjectsOther
Subjects with PD with and without freezing of gait (FoG) will undergo a biomechanical assessment during a FoG provocation protocol in both the dopaminergic "on" and "off" state.
| Study group | Role | What they receive |
|---|---|---|
| Parkinson's disease without FoG | Subjects with Parkinson's disease that do not have freezing of gait observed during motor assessment while both on or off dopaminergic medication who have undergone Brain PET imaging of 11C-DBTZ, 18F-FEOBV (vesicular acetylcholine transporter, and 11C-PIB (beta-amyloid). Receives: Other: Detailed motor testing, including FoG, in PD subjects | |
| Parkinson's disease with FoG only while off-meds | Subjects with Parkinson's disease that have freezing of gait observed during motor assessment only while off dopaminergic medication who have undergone Brain PET imaging of 11C-DBTZ, 18F-FEOBV (vesicular acetylcholine transporter, and 11C-PIB (beta-amyloid). Receives: Other: Detailed motor testing, including FoG, in PD subjects | |
| Parkinson's disease with FoG worse while off-meds | Subjects with Parkinson's disease that have freezing of gait observed during motor assessment while both on and off dopaminergic medication, but greater severity of FoG under off-med, who have undergone Brain PET imaging of 11C-DBTZ, 18F-FEOBV (vesicular acetylcholine transporter, and 11C-PIB (beta-amyloid). Receives: Other: Detailed motor testing, including FoG, in PD subjects | |
| Parkinson's disease with FoG equivalent between on and off meds | Subjects with Parkinson's disease that have freezing of gait observed during motor assessment while both on and off dopaminergic medication, with no apparent effect of dopaminergic medication on FoG, who have undergone Brain PET imaging of 11C-DBTZ, 18F-FEOBV (vesicular acetylcholine transporter, and 11C-PIB (beta-amyloid). Receives: Other: Detailed motor testing, including FoG, in PD subjects |
What is being measured
The primary outcome is the main question the study is designed to answer.
L-DOPA Insensitivity
Participants are considered as L-DOPA insensitive if their freezing of gait is not observed to be any different between motor assessment while on dopaminergic medication and off dopaminergic medication.
Measured: through study completion, an average of 6 months
Striatal FEOVB PET Binding
Parametric distribution volume ratio (DVR) of FEOVB, a cholinergic PET tracer, in the striatum.
Measured: through study completion, an average of 6 months
Striatal DTBZ PET Binding
Parametric distribution volume ratio (DVR) of DTBZ, a dopaminergic PET tracer, in the striatum.
Measured: through study completion, an average of 6 months
Striatal PIB PET Binding
Parametric distribution volume ratio (DVR) of PIB, an amyloid PET tracer, in the striatum.
Measured: through study completion, an average of 6 months
Secondary outcomes (1)
Serotonergic Innervation of Striatum and Freezing
Serotonergic innervation of striatum as assessed by DASB PET scan across freezer groups.
Measured: through study completion, an average of 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2018
- Study start7 Jun 2016
- Primary completion26 May 2021
- Study completion26 May 2021
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 VA Office of Research and DevelopmentThe 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- University of Michigan
- Responsible party
- Sponsor
- Investigators
- Nicolaas I Bohnen, MD PhD, Principal investigator, VA Ann Arbor Healthcare System, Ann Arbor, MI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03647137
- Sponsor's protocol ID
- B1631-I
- Other IDs
- HUM00110351
- Acronym
- FOG
- Status last verified
- Mar 2023
- First submitted
- 23 Aug 2018
- Last updated
- 5 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Amyloidopathy, Cholinopathy, Dopamine Responsiveness and Freezing of Gait in PD
- ClinicalTrials.gov ID
- NCT03647137
- Acronym / sponsor ID
- FOG / B1631-I
- Conditions
- Parkinson's Disease
- Keywords
- freezing of gait, amyloid, cholinergic, mobility, PET, imaging, MRI
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- University of Michigan
- Study start
- 7 Jun 2016 (actual)
- Primary completion
- 26 May 2021 (actual)
- Study completion
- 26 May 2021 (actual)
- First posted
- 27 Aug 2018 (actual)
- Results
- Posted 5 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Early stage Parkinson disease (PD) is characterized by a 'honeymoon' phase in terms of responsiveness of motor symptoms, including gait, to dopaminergic pharmacotherapy. Advancing PD is associated with disabling axial motor complications, such as freezing of gait (FoG), with decreased or even refractory dopamine responsiveness in over 50% of patients. The management of dopamine resistant gait problems represents the most important unmet need in PD. This study will related detailed motor testing to brain PET imaging to see if certain molecules (or lack thereof) involved with neurologic transmission in the brain are involved with FoG.
Detailed description
Early stage Parkinson disease (PD) is characterized by a 'honeymoon' phase in terms of responsiveness of motor symptoms, including gait, to dopaminergic pharmacotherapy. Advancing PD is associated with disabling axial motor complications, such as freezing of gait (FoG), with decreased or even refractory dopamine responsiveness in over 50% of patients. The management of dopamine resistant gait problems represents the most important unmet need in PD. At present, there is no biomarker of FoG in patients with PD as there is a lack of mechanistic understanding of dopamine nonresponsiveness of FoG. The investigators have previously identified cholinergic denervation as a prominent factor related to both falls and gait slowing in PD. The investigators recently identified that cortical -amyloid deposition not only associates with cognitive decline but also with postural instability and gait difficulties in PD. In this proposal, the investigators present preliminary data suggesting that FoG is associated with either cholinopathy, amyloidopathy or both in PD. The investigators propose to test the novel hypothesis that comorbid amyloidopathy may be a possible mechanistic factor underlying the poor response of FoG to dopaminergic therapy in advancing PD. In contrast, isolated cholinopathy would be expected to be associated with preserved dopamine responsiveness of FoG. For this purpose, the investigators propose to perform detailed motor, including FoG, testing in PD patients "on" and "off" their dopaminergic medications and relate this to dopaminergic 11C-dihydrotetrabenazine (DTBZ), vesicular acetylcholine transporter 18F-fluoroethoxybenzovesamicol (FEOBV) and -amyloid 11C-labeled Pittsburgh Compound-B (PIB) brain PET imaging in PD subjects with and without FoG. Furthermore, based on recent clinical observations that serotoninergic drugs, like the popular anti-depressant selective serotonin reuptake inhibitor (SSRI) drugs, are associated with significantly lower build- up of -amyloid plaques in the elderly population, and based on the investigators' subsequent observation of an intriguing inverse relationship between -amyloid plaque deposition and striatal serotoninergic terminal in PD, the investigators propose to perform an exploratory sub-study to test a new hypothesis that PD subjects with FoG will exhibit not only higher striatal -amyloid but also lower striatal serotoninergic innervation (as determined by 11C-DASB serotonin PET imaging) compared to PD subjects without FoG. If confirmed, positive findings in this study would allow the identification of different PD subgroups ('personalized medicine'), such as presence amyloidopathy or cholinopathy, to select patients for targeted pharmacotherapies to potentially prevent the development of FoG (anti-amyloid, such as serotoninergic drugs) or manage its clinical manifestation (cholinergic augmentation therapy) in order to preserve and maintain a good quality of life in individuals with PD.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Parkinson's disease without FoG | – | Other: Detailed motor testing, including FoG, in PD subjectsSubjects with Parkinson's disease that do not have freezing of gait observed during motor assessment while both on or off dopaminergic medication who have undergone Brain PET imaging of 11C-DBTZ, 18F-FEOBV (vesicular acetylcholine transporter, and 11C-PIB (beta-amyloid). |
| Parkinson's disease with FoG only while off-meds | – | Other: Detailed motor testing, including FoG, in PD subjectsSubjects with Parkinson's disease that have freezing of gait observed during motor assessment only while off dopaminergic medication who have undergone Brain PET imaging of 11C-DBTZ, 18F-FEOBV (vesicular acetylcholine transporter, and 11C-PIB (beta-amyloid). |
| Parkinson's disease with FoG worse while off-meds | – | Other: Detailed motor testing, including FoG, in PD subjectsSubjects with Parkinson's disease that have freezing of gait observed during motor assessment while both on and off dopaminergic medication, but greater severity of FoG under off-med, who have undergone Brain PET imaging of 11C-DBTZ, 18F-FEOBV (vesicular acetylcholine transporter, and 11C-PIB (beta-amyloid). |
| Parkinson's disease with FoG equivalent between on and off meds | – | Other: Detailed motor testing, including FoG, in PD subjectsSubjects with Parkinson's disease that have freezing of gait observed during motor assessment while both on and off dopaminergic medication, with no apparent effect of dopaminergic medication on FoG, who have undergone Brain PET imaging of 11C-DBTZ, 18F-FEOBV (vesicular acetylcholine transporter, and 11C-PIB (beta-amyloid). |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Community sample recruited from the following sources 1. UMHS Movement Disorders Clinics 2. VA Ann Arbor HS Movement Disorders Clinic 3. Existing studies at Functional Neuroimaging, Cognitive, and Mobility Lab at the University of Michigan
Key inclusion criteria (4 listed)
- PD based on the United Kingdom Parkinson's Disease Society Brain Bank
- Diagnostic Research Criteria with or without Freezing of Gait
- Duration of Disease > 5 years
- Mini-Mental State Examination (MMSE) > 23
Key exclusion criteria (12 listed)
- Dementia
- Dementia with Lewy Bodies
- Other disorders which may resemble PD
- Subjects on neuroleptic, anticholinergic (trihexyphenidyl, benztropine) or cholinesterase inhibitor drugs
- Evidence of a stroke or mass lesion on structural brain imaging (MRI)
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 |
|---|---|---|
| Detailed motor testing, including FoG, in PD subjectsSubjects with PD with and without freezing of gait (FoG) will undergo a biomechanical assessment during a FoG provocation protocol in both the dopaminergic "on" and "off" state. | Other | Parkinson's disease with FoG equivalent between on and off meds, Parkinson's disease with FoG only while off-meds, Parkinson's disease with FoG worse while off-meds, Parkinson's disease without FoG |
Primary outcome
L-DOPA Insensitivity
Time frame: through study completion, an average of 6 months
Participants are considered as L-DOPA insensitive if their freezing of gait is not observed to be any different between motor assessment while on dopaminergic medication and off dopaminergic medication.
Striatal FEOVB PET Binding
Time frame: through study completion, an average of 6 months
Parametric distribution volume ratio (DVR) of FEOVB, a cholinergic PET tracer, in the striatum.
Striatal DTBZ PET Binding
Time frame: through study completion, an average of 6 months
Parametric distribution volume ratio (DVR) of DTBZ, a dopaminergic PET tracer, in the striatum.
Striatal PIB PET Binding
Time frame: through study completion, an average of 6 months
Parametric distribution volume ratio (DVR) of PIB, an amyloid PET tracer, in the striatum.
1 secondary outcome
Serotonergic Innervation of Striatum and Freezing
Time frame: through study completion, an average of 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2024.
- 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.
Nicolaas I Bohnen, MD PhD principal investigator
VA Ann Arbor Healthcare System, Ann Arbor, MI
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Parkinson's Disease, run by VA Office of Research and Development 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 12 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 5 Jan 2024. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jan 2024). 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?
L-DOPA Insensitivity (time frame: through study completion, an average of 6 months). The study lists 4 primary outcomes in all. 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 5 Jan 2024.