The Effect of Donepezil on Gait and Balance in Parkinson's Disease

September 9, 2021 updated by: Amie Hiller, MD, Oregon Health and Science University

A Randomized, Double-blind, Placebo Controlled, Crossover Study to Evaluate the Effect of Donepezil on Gait and Balance in Parkinson's Disease

This study involves Parkinson's disease (PD). Symptoms include slow movement, tremor, and muscle rigidity. Current medications for the treatment of PD do not improve gait and balance difficulties in individuals with PD. Donepezil (study drug) has been found to reduce falls in individuals with PD. The mechanism in which this reduction of falls occurs is unclear. The investigators study will look at what aspects of gait and balance are improved by the study drug. The study drug is not approved to treat PD in the United States or other countries because we do not know enough about it.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Parkinson's disease (PD) is a common neuro-degenerative disease affecting about 2% of the adult population in the United States over the age of 65. Some of the most disabling symptoms of Parkinson's disease are balance and gait dysfunction, leading to falls. These symptoms do not respond to current dopamine directed therapies. Evidence from both pathologic studies and advanced imaging has demonstrated that a cholinergic deficiency in the thalamus and basal ganglia is found in individuals with PD who fall compared to non-fallers. The central acting acetylcholine esterase inhibitor, donepezil, has been demonstrated to decrease falls in individuals with PD. The mechanism by which falls decreased is unknown. Our open label pilot data indicates that donepezil can improve quantitative measures of balance in individuals with PD. Suggesting that improvements in balance in the mechanism by which donepezil reduces falls. Our goal is to determine whether donepezil will:

  • Improve quantitative measures of balance in subjects with Parkinson's disease compared to placebo.
  • Improve quantitative measures of gait in subjects with Parkinson's disease compared to placebo.
  • Improve cognitive measures in non-demented subjects with Parkinson's disease.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Oregon
      • Portland, Oregon, United States, 97239
        • Parkinson's Center of Oregon - Oregon Health and Science University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Idiopathic Parkinson's disease, defined by the UK Brain Bank criteria, with a Hoehn and Yahr score of 2 to 4
  • Treated with levodopa for at least a year and on a stable antiparkinsonian regimen for at least one month
  • Abnormal computerized dynamic posturography (CDP) on screening defined as a composite score below 65 (range 1-100)

Exclusion Criteria:

  • Dementia defined by MMSE less than 27
  • Other medical conditions other than PD affecting balance or gait as determined by the investigators
  • Unable to stand unassisted for 30 minutes
  • Current use of an acetylcholinesterase inhibitors or drugs with known anticholinergic properties
  • Medical or psychiatric co-morbidities that may interfere with compliance or might place subject in danger as determined by the investigators

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Donepezil, Then Placebo
Donepezil 5 mg a day for weeks 1 - 3, if tolerated increased to 10 mg a day for weeks 4 - 6. After a washout period of 4 weeks, placebo 5 mg a day for weeks 1 - 3, if tolerated increased to 10 mg a day for weeks 4 - 6.
Drug: Donepezil
Use 1 capsule (5 mg) of donepezil once per day for first 21 days than donepezil 10mg qday for 21 days.
Other Names:
  • Aricept
Drug: Placebo
Use 1 capsule (5 mg) once per day for first 21 days than 10mg qday for 21 days.
Other Names:
  • Sugar Pill
Experimental: Placebo, Then Donepezil

Placebo 5 mg a day for weeks 1 - 3, if tolerated increased to 10 mg a day for weeks 4 - 6.

After a washout period of 4 weeks, donepezil 5 mg a day for weeks 1 - 3, if tolerated increased to 10 mg a day for weeks 4 - 6.
Drug: Donepezil
Use 1 capsule (5 mg) of donepezil once per day for first 21 days than donepezil 10mg qday for 21 days.
Other Names:
  • Aricept
Drug: Placebo
Use 1 capsule (5 mg) once per day for first 21 days than 10mg qday for 21 days.
Other Names:
  • Sugar Pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensory Organization Test - Composite Score
Time Frame: Change from Day 1 of each treatment phase to Day 42 of each treatment phase
Balance was measured using the Sensory Organization test (SOT) on the NeuroCom Balance Master Clinical Research System platform (Neurocom International, Inc), which tests sway in 6 conditions, eyes open, eyes closed, and a moving visual surround first with a stable platform then with a moving platform. Center of Pressure (CoP) was calculated from the recordings. Forces and moments were recorded at 100Hz sampling frequency. A change score from the beginning of each treatment phase (placebo or active drug) to the end of the treatment phase. The SOT is scored on an interval scale with the highest possible score of 100 indicating no sway at all. The lowest possible score of 0 indicates the trial was stopped due to an impending fall. Higher scores are indicative of better balance (greater stability).
Change from Day 1 of each treatment phase to Day 42 of each treatment phase
Sensory Organization Test (SOT) - Condition 4 (Eyes Open, Moving Surround, Stable Platform).
Time Frame: Change from Day 1 of each treatment phase to Day 42 of each treatment phase
Condition 4 of the Sensory Organization Test. The participants eyes are open as the surround moves and the platform remains stable. A change score from the beginning of each treatment phase (placebo or active drug) to the end of the treatment phase. The SOT is scored on an interval scale with the highest possible score of 100 indicating no sway at all. The lowest possible score of 0 indicates the trial was stopped due to an impending fall. Higher scores are indicative of better balance (greater stability).
Change from Day 1 of each treatment phase to Day 42 of each treatment phase

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Trails B - A
Time Frame: Change from Day 1 of each treatment phase to Day 42 of each treatment phase
The Trail Making Test (TMT) consists of two parts (A & B) in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. The test provides information about visual search speed, scanning, speed of processing, and executive functioning. Part A measures processing speed and part B measures executive functioning. The TMT is time to complete each part of the test in seconds. Higher scores indicate greater impairment. Subtracting part A from part B (Trails B-A) is theorized to reduce the influence of the working memory and visuo-spatial demands and, therefore, provides a relatively pure indicator of executive function. A change score from the beginning of each treatment phase (placebo or active drug) to the end of the treatment phase.
Change from Day 1 of each treatment phase to Day 42 of each treatment phase

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oregon Health and Science University

Investigators

  • Principal Investigator: Seth Kareus, MD, Movement Disorders Program - Parkinson's Center of Oregon - Oregon Health and Science University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2011

Primary Completion (Actual)

April 1, 2012

Study Completion (Actual)

July 1, 2012

Study Registration Dates

First Submitted

January 12, 2012

First Submitted That Met QC Criteria

January 25, 2012

First Posted (Estimate)

January 30, 2012

Study Record Updates

Last Update Posted (Actual)

October 5, 2021

Last Update Submitted That Met QC Criteria

September 9, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OHSU-7363

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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