Investigating the Cholinergic Contribution to Gait Dysfunction in Parkinson's Disease

NCT06903910 | Completed Phase 2 FDA Drug

• 1 other identifier: HSR230410
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

People with Parkinson's disease often experience problems with 'gait' and balance. Gait refers to the way a person moves while walking, such as their speed and length of steps. People with Parkinson's may experience slowness of movement, shuffle their feet, or have periods of 'freezing', during which their feet feel like they are stuck to the floor. Some people may struggle to maintain their balance and fall. These symptoms are frequently disabling and can lead to a worse quality of life. The nervous system is your body's messaging system - it helps different parts of your body communicate with one another. Neurotransmitters are chemicals that deliver those messages from one part of the body to another. The purpose of this study is to determine if the use of ARICEPT (Donepezil hydrochloride) improves gait and balance and its relation to the size of an area of the brain called "Cholinergic Nucleus 4" (Ch4). The study team is also studying how degeneration (breakdown and eventual loss) in Ch4 contributes to problems with gait and balance. One way this may happen is through the loss of a chemical in the brain called acetylcholine. Acetylcholine is a neurotransmitter and its activity is associated with alertness, thinking, and the ability to move. Taking a drug that increases acetylcholine, such as ARICEPT, may improve gait and balance. By better understanding this relationship, we may be able to improve the treatment of gait and balance problems in the future.

Conditions

Parkinson Disease

Keywords

Gait; Cholinergic

Outcome Measures

Primary Outcomes (1)

• Relationship between Ch4 GMD and gait speed

  We hypothesize that lower baseline Ch4 GMD will be associated with slower baseline gait speed

  Baseline

Secondary Outcomes (1)

• Relationship between baseline Ch4 GMD and gait response to donepezil

  From enrollment to the end of treatment at 12 weeks

Study Arms (1)

Donepezil

EXPERIMENTAL

Patients with Parkinson's disease and gait dysfunction will be enrolled. We will measure gait metrics and obtain an MRI at baseline, then everyone will begin donepezil (5mg nightly for 4 weeks, followed by 10mg nightly). There will be a telephone check in at week 6, then at week 12 they will return for repeat gait metrics

Drug: Donepezil (Aricept)

Interventions

Donepezil (Aricept) DRUG

Donepezil is a cholinesterase inhibitor tablet taken by mouth once nightly

Donepezil

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of PD by a neurologist as per UK Brain Bank criteria
• Age 40 or older
• Clinical evidence of gait dysfunction, as determined by a movement disorders neurologist.
• Willingness and ability to comply with scheduled visits and study procedures.
• Actively treated with a stable dose of levodopa or other anti-parkinsonian medications.
• Able to ambulate without the use of an assistive device.
• Serum chemistry from blood obtained at screening will need to be free from evidence of renal injury (elevated creatinine) or other significant metabolic abnormalities at the discretion of the examiner within 28 days of study initiation.
• Subject agrees not to participate in another study with an investigational drug/treatment during this study and for 3 months following study completion.
• Female subjects must not be breastfeeding and must have a negative serum pregnancy test at Visit 1. Women of childbearing potential (WOCBP) must use one of the following acceptable birth control methods as specified before enrollment and throughout the trial:
• Surgical sterilization (bilateral tubal occlusion/ligation) prior to signing the informed consent form (ICF).
• Intrauterine device in place for at least 3 months before the first dose of study drug and throughout the trial.
• Barrier method (condom or diaphragm) with spermicide for at least 30 days before the first dose of the study drug and throughout the trial.
• Surgical sterilization of the male partner (vasectomy at least 6 months before the first dose of study drug).
• Hormonal contraceptives with a barrier method for at least 3 months before the first dose of the study drug and throughout the trial.
• Female subjects are not considered to be of childbearing potential if they meet at least one of the following criteria as documented by the Investigator:

You may not qualify if:

• Current use of donepezil, rivastigmine, galantamine, or memantine
• Score of 3 or higher on the Anticholinergic Cognitive Burden Scale
• Presence of a deep brain stimulator, or implantation of a deep brain stimulator during the study
• Montreal Cognitive Assessment (MoCA) score less than 21
• Known allergic reactions to donepezil or piperidine derivatives
• Use of a different investigational drug/treatment within 3 months before the study
• Presence of bradycardia for bradycardia (\<60bpm) and other significant arrhythmias (not counting simple first-degree heart block), severe COPD, severe asthma, peptic ulcer disease, or other severe, acute medical comorbidities that could affect the outcome of the study, for example acute end-stage CHF or acute pneumonia
• Inability to obtain a brain MRI (presence of ferromagnetic metal inside the body, severe claustrophobia, etc)

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Donepezil

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Study Officials

• William A Dalrymple, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 25, 2025
• First Posted: April 1, 2025
• Study Start: November 1, 2024
• Primary Completion: June 30, 2025
• Study Completion: January 31, 2026
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)