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Parkinson DiseaseNCT05459753

Cholinergic Mechanisms of Attentional-motor Integration and Gait Dysfunction in Parkinson Disease (UDALL)

A study testing (18)F]fluoroethoxybenzovesamicol ([(18)F (FEOBV) PET and Dihydrotetrabenazine (DTBZ) PET in people with Parkinson Disease and Progressive Supranuclear Palsy, run by University of Michigan at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

To perform a prospective cohort study with [(18)F]fluoroethoxybenzovesamicol (FEOBV) brain PET at baseline and 2-year follow-up in PD subjects at risk of conversion to non-episodic and episodic (falls and FoG) PIGD motor features and cognitive changes at the same time points. Read more about this study

Who is it for?
Ages 21 years and olderHealthy volunteers can take part
What is being tested?
(18)F]fluoroethoxybenzovesamicol ([(18)F (FEOBV) PET and Dihydrotetrabenazine (DTBZ) PET
Could I receive a placebo?
No, everyone receives an active treatment
How many people
125 participants
Where
1 siteUnited States
Study dates
1 Mar 2022to 30 Jun 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

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 21 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Age ≥21 for normal control subjects (Male/Female) and ≥45 for Parkinson's disease (PD), Progressive supranuclear palsy (PSP), or Alzheimer's disease (AD) participants (Male/Female).
  • For normal control subjects, no significant neurological or psychiatric symptoms and normal neuropsychological examination for age.
  • PD diagnosis (with or without Mild Cognitive Impairment/dementia) will follow the Movement Disorder Society-revised clinical diagnostic criteria for PD or Parkinson-PSP patients.
  • Modified Hoehn and Yahr stages 1-4.
  • AD subjects meeting the criteria listed in Guy M. McKhann et al.
  • All PD subjects are required to have nigrostriatal dopaminergic denervation as demonstrated by vesicular monoaminergic transporter type-2 (VMAT) [18F]9-fluoropropyl-(+)-dihydrotetrabenazine (DTBZ) positron emission tomography (PET) imaging. This may be based on a prior DTBZ PET scan or the DTBZ PET scan performed as part of this study.

Who cannot join

  • Disorders which may resemble PD, such as dementia with Lewy bodies, vascular dementia, normal pressure hydrocephalus, multiple system atrophy, corticobasal ganglionic degeneration, or toxic causes of parkinsonism. The use of the Movement Disorder Society-revised clinical diagnostic criteria will mitigate the inclusion of PD subjects with atypical parkinsonism.
  • Subjects on neuroleptic, anticholinergic (trihexyphenidyl, benztropine), or cholinesterase inhibitor drugs. Subjects with prior exposure to disallowed medications may be eligible if there has been an interval of > 2 months off these medications.** Note that patients on pimavanserin will be eligible.
  • Evidence of a large vessel stroke in a clinically relevant area (cerebral cortex, basal ganglia, thalamus) or mass lesion on structural brain imaging (MRI or CT).**
  • Participants in whom 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.**
  • Subjects limited by previous participation in research procedures involving ionizing radiation.**
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  • Pregnancy (test within 48 hours of each PET session) or breastfeeding.**
  • History of deep brain stimulation surgery.**
  • Suicidality (responses 2 or 3 for question 9 on the Beck Depression Inventory).
  • Subjects from the previous U-M Udall Center cohort who have developed a contraindication for neuroimaging procedures (Exclusion criteria #4 - #9) or have started taking cholinergic medications (Exclusion criterion #3) will be eligible to continue their participation in clinical assessments but will not be referred to neuroimaging assessments.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Michigan - Michigan Medicine

    Ann Arbor, Michigan, 48106

Other trials in United States

About this study

To perform a prospective cohort study with [(18)F]fluoroethoxybenzovesamicol (FEOBV) brain PET at baseline and 2-year follow-up in PD subjects at risk of conversion to non-episodic and episodic (falls and FoG) PIGD motor features and cognitive changes at the same time points.

Read the detailed description

Postural instability and gait difficulty (PIGD) motor and cognitive changer features are common in Parkinson disease (PD), and a significant cause of treatment-refractory disability. Accumulating evidence implicates cholinergic systems dysfunctions as significant contributors to gait and balance and cognitive impairment. During the initial funding period, the investigators established the vesicular acetylcholine transporter (VAChT) ligand FEOBV, which uniquely assesses cholinergic terminal density in high density regions such as the striatum. Recent cross-sectional findings suggest that people with Parkinson's (PwP) participants with isolated falls and those with freezing of gait (FoG) status share common cholinergic deficits in the thalamus (lateral geniculate nucleus (LGN)) and striatum (caudate) with more extensive striatal, limbic, and prefrontal VAChT reductions in PwP with FoG. These data suggest that SChI deficits are a common denominator in the etiology of falls and FoG. These results emphasize the need to understand PIGD, falls, and FoG as products of cholinergic projection dysfunctions within the framework of failing Attentional-Motor Integration (AMI) combined with failures of additional multisensory and cognitive integration.

There is novel preliminary data that cholinergic deficits of the medial geniculate nucleus (MGN) and the entorhinal cortex (ERC) are robustly associated with non-episodic PIGD deficits. These results imply a significant role of impaired sensorimotor integration underlying non-episodic PIGD motor features in PwP. There is also have novel data that cholinergic changes in the cingulo-opercular task control network (COTC) are a robust correlate of cognitive changes in PwP. The overarching goal of this project is to investigate the evolution of cholinergic deficits within multisensory, cognitive and motor integration brain regions and development of PIGD features and cognitive deficits in PwP. This study will perform a prospective cohort study with FEOBV brain PET at baseline and 2-year follow-up.

Being tested
(18)F]fluoroethoxybenzovesamicol ([(18)F (FEOBV) PET, Dihydrotetrabenazine (DTBZ) PET
Keywords
Parkinson's Disease, Parkinson, Parkinson's, Freezing of Gait, FOG, PIGD
Medical subject headings
Parkinson Disease, Supranuclear Palsy, Progressive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • (18)F]fluoroethoxybenzovesamicol ([(18)F (FEOBV) PETRadiation

    Participants will receive an injection of 8 mCi [18F]FEOBV PET tracer and undergo a CT of the head.

  • Dihydrotetrabenazine (DTBZ) PETRadiation

    Participants will receive an injection of 15 mCi [11C]DTBZ PET tracer and undergo a CT of the head.

Study groups in NCT05459753
Study groupRoleWhat they receive
Parkinson's DiseaseExperimentalIndividuals with idiopathic Parkinson's disease.
Receives: Radiation: (18)F]fluoroethoxybenzovesamicol ([(18)F (FEOBV) PET; Radiation: Dihydrotetrabenazine (DTBZ) PET

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Interval change on the Unified Parkinson's disease rating scale (UPDRS) motor rating scale over a 2-yr period

    Interval change baseline vs 2-yr follow-up on the UPDRS motor score. UPDRS motor section is scored from 0-132, with higher scores indicating more severe motor symptoms.

    Measured: At Baseline and at 2-year follow up

  2. Cholinergic brain PET FEOBV PET distribution volume ratio (DVR) interval change over a 2-yr period

    Interval change baseline vs 2-yr follow in cholinergic brain FEOBV PET DVR

    Measured: At Baseline and at 2-year follow up

  3. Cognitive 2-yr interval change on the Montreal Cognitive Assessment (MoCa) cognitive scale

    Interval change baseline vs 2-yr follow-up on the Montreal Cognitive Assessment (MoCa) cognitive scale. The MoCa is scored out of 30, with higher scores indicating better cognition.

    Measured: At Baseline and at 2-year follow up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jul 2022
  2. Study start1 Mar 2022
  3. Primary completion30 Jun 2027 (estimated)
  4. Study completion30 Jun 2027 (estimated)

Resources

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 N/A
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
125 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05459753
Sponsor's protocol ID
HUM00197590
Other IDs
1P50NS123067-01
Status last verified
Jul 2026
First submitted
1 Jul 2022
Last updated
27 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Barr J, Vangel R, Kanel P, Roytman S, Pongmala C, Albin RL, Scott PJH, Bohnen NI. Topography of Cholinergic Nerve Terminal Vulnerability and Balance Self-Efficacy in Parkinson's Disease. J Integr Neurosci. 2024 Sep 24;23(9):178. doi: 10.31083/j.jin2309178.

    PubMed 39344233

Questions about this trial

What is this clinical trial studying?

A study testing (18)F]fluoroethoxybenzovesamicol ([(18)F (FEOBV) PET and Dihydrotetrabenazine (DTBZ) PET in people with Parkinson Disease and Progressive Supranuclear Palsy, 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 6 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: under way, not looking for participants, as of the sponsor's last update on 27 Jul 2026. 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?

This study is still under way. Results are not available in the source record yet.

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?

Interval change on the Unified Parkinson's disease rating scale (UPDRS) motor rating scale over a 2-yr period (time frame: At Baseline and at 2-year follow up). The study lists 3 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 NCT05459753, 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 Jul 2026.

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