Striatal and Extra-Striatal Cholinergic Terminal Density in LRRK2-PD Mutation

NCT07642908 | Recruiting DMC

• 1 other identifier: HUM00276006
• Study Type: observational
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This study explores how a specific genetic mutation of leucine-rich repeat kinase 2 (LRRK2) affects individuals with Parkinson's disease (PD), comparing those with the mutation to others with Parkinson's disease and without the mutation (iPD). Participants will complete positron emission tomography (PET) and magnetic resonance imaging (MRI) brain imaging, cognitive tests, motor tests, sensory tests, and questionnaires. The aims of this study are to compare brain chemicals in LRRK2 PD patients with iPD patients and to correlate brain chemicals with motor and cognitive tests in LRRK2 PD and iPD patients.

Conditions

Parkinson Disease

Keywords

Parkinson's Disease; LRRK; LRRK2; functional neuroimaging

Outcome Measures

Primary Outcomes (6)

• Cholinergic Differences Between leucine-rich repeat kinase 2 (LRRK2) Parkinson's disease (PD) and Idiopathic/non-LRRK2 PD (iPD)

  The cholinergic system changes for people with PD. It is anticipated that LRRK2-PD will demonstrate different cholinergic expression compared to iPD. 18F-fluoroethoxybenzovesamicol (\[18F\]FEOBV) PET scans will be used to measure Vesicular acetylcholine transporter (VAChT). Higher levels of VAChT binding indicate higher levels of acetylcholine in the brain. Lower levels of VAChT binding indicate lower levels of acetylcholine in the brain. VAChT levels will be compared across brain regions for LRRK2 vs iPD.

  Baseline

• Dopaminergic Differences Between LRRK2-PD and iPD

  The dopaminergic system changes for people with PD. It is anticipated that LRRK2-PD will demonstrate different dopaminergic expression compared to iPD. N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methyl-phenyl)nortropane (\[¹¹C\]PE2i) PET scans will be used to measure dopamine transporter (DAT). Higher levels of DAT binding indicate higher levels of dopamine in the brain. Lower levels of DAT binding indicate lower levels of dopamine in the brain. DAT levels will be compared across brain regions for LRRK2 vs iPD.

  Baseline

• Association of Cholinergic Data With Cognition in LRRK2-PD

  Association of the global average cholinergic uptake (represented by VAChT uptake) with the global average cognitive z-score of individuals with LRRK2-PD.

  Baseline

• Association of Cholinergic Data With Postural Instability and Gait Difficulties (PIGD) in LRRK2-PD

  Association of the global average cholinergic uptake (represented by VAChT uptake) with the global average PIGD score of individuals with LRRK2-PD.

  Baseline

• Association of Dopaminergic Data With Cognition in LRRK2-PD

  Association of the global average dopaminergic uptake (represented by DAT uptake) with the global average cognitive z-score of individuals with LRRK2-PD.

  Baseline

• Association of Dopaminergic Data With PIGD in LRRK2-PD

  Association of the global average dopaminergic uptake (represented by DAT uptake) with the global average PIGD score of individuals with LRRK2-PD.

  Baseline

Study Arms (2)

LRRK2

Individuals with PD and LRRK2 genetic mutation.

iPD

Individuals with PD and without LRRK2 genetic mutation (Pre-existing cohorts, not recruiting).

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals with Parkinson's disease and the LRRK2 genetic mutation.

You may qualify if:

• Male or Female, age 45 years and over.
• Diagnosis of PD based on the United Kingdom Parkinson's Disease Society Brain Bank Diagnostic Research Criteria (Hughes et al., 1992).
• Presence of LRRK2 mutation as confirmed by referral from UM Movement Disorders clinic, medical record review, or participation in the PDGENEration study.

You may not qualify if:

• Evidence of atypical parkinsonism.
• Contra-indications to MR imaging including but not limited to pacemakers, aneurysm clips, intraocular metal, cochlear implant, or severe claustrophobia.
• Evidence of large vessel stroke or mass lesion on MRI.
• Regular use of typical anti-cholinergic drugs or cholinesterase inhibitors.
• History of deep brain stimulation surgery.
• Pregnant or nursing.
• Suicidal ideation, as indicated by a response of 2 or 3 on question 9 of the Beck Depression Inventory.
• Cognitive impairment that results in the inability to give consent, as demonstrated by the Decision Making Capacity Tool.
• Any other condition or criterion that would preclude safe and meaningful participation in the study.

Sponsors & Collaborators

• University of Michigan: lead
• Michael J. Fox Foundation for Parkinson's Research: collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48106, United States

RECRUITING

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Prabesh Kanel, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nathan Alexander, BSc

CONTACT

734-998-6894; natealex@med.umich.edu

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Assistant Professor of Radiology

Study Record Dates

• First Submitted: May 13, 2026
• First Posted: June 11, 2026
• Study Start: September 18, 2025
• Primary Completion (Estimated): September 17, 2026
• Study Completion (Estimated): September 17, 2026
• Last Updated: June 11, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will be made available within 12 months of primary study completion (by September 2027) and will remain available for a minimum of 5 years.
• Access Criteria: Researchers seeking access to de-identified data must submit a brief research proposal to the principal investigator and execute a data use agreement in accordance with University of Michigan institutional policies or request access to the data via PPMI.

Locations

US (1)