Amyloidopathy, Cholinopathy, Dopamine Responsiveness and Freezing of Gait in PD

NCT03647137 | Completed Results

• 2 other identifiers: B1631-IHUM00110351
• Study Type: observational
• Target: 53
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Parkinson's Disease

Keywords

freezing of gait; amyloid; cholinergic; mobility; PET; imaging; MRI

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  through study completion, an average of 6 months

Secondary Outcomes (1)

• Serotonergic Innervation of Striatum and Freezing

  through study completion, an average of 6 months

Study Arms (4)

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).

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).

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).

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).

Other: Detailed motor testing, including FoG, in PD subjects

Interventions

Detailed motor testing, including FoG, in PD subjects OTHER

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.

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

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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

You may qualify if:

• 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

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead
• University of Michigan: collaborator

Study Sites (1)

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, 48105, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Saliva for DNA Serum (approx. 4ml)

MeSH Terms

Conditions

Parkinson Disease; Alzheimer Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dementia; Tauopathies; Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

The sample was predominantly male limiting generalization to the broader PD patient population.

Results Point of Contact

• Title: Dr. Nicolaas Bohnen
• Organization: Department of Veteran Affairs

nicolaas.bohnen@va.gov

7347697100

Study Officials

• Nicolaas I Bohnen, MD PhD

  VA Ann Arbor Healthcare System, Ann Arbor, MI

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2018
• First Posted: August 27, 2018
• Study Start: June 7, 2016
• Primary Completion: May 26, 2021
• Study Completion: May 26, 2021
• Last Updated: January 5, 2024
• Results First Posted: January 5, 2024

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)