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Completed

NCT Number: NCT02206620

Effects of Cholinergic Augmentation on Measures of Balance and Gait

This study will compare the effects of placebo and donepezil, a drug that helps conserve concentrations of the neurotransmitter, acetylcholine, on measures of balance and gait in subjects with Parkinson's disease (PD). This study is a double-blind, placebo controlled, cross-over randomized clinical trial. Short-latency afferent inhibition (SAI), a physiological index of cholinergic function will be measured to determine if the deficits in balance and gait correlate with abnormalities of the SAI and if SAI is altered by donepezil as a measure of drug efficacy. Cognitive tests like the Attention Network Test (ANT) will be administered to determine if changes in gait and balance are mediated by changes in attention.

The results of this study will be the most direct test of the hypothesized role of cholinergic neurons and the neurotransmitter, acetylcholine in terms of gait and balance. The study is exploratory because it is not known whether donepezil will affect gait, balance or attention, nor which measures of gait, balance or attention will be sensitive to drug manipulation. The study's immediate goal is to determine the potential utility of cholinergic manipulation as a strategy for preventing or treating balance and gait dysfunction in PD. The findings of this trial are intended to lead to more sharply focused questions about the role of cholinergic neurons in balance and gait and eventually to Phase II B trials to determine clinical utility of cholinergic manipulation to prevent falls and improve mobility.

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Key information

Conditions

Parkinson's Disease Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Movement Disorders Nervous System Diseases Neurodegenerative Diseases Parkinson Disease Parkinsonian Disorders Synucleinopathies

Age range

30 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Oregon Health & Science University

Portland, Oregon, 97239-3098, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 30 years old or older
  • Diagnosis of idiopathic Parkinson's disease
  • Stand unassisted (without use of an assistance device) and walk continuously for at least 2 minutes.

Exclusion criteria

  • musculoskeletal disorders that affect standing and walking
  • Uncorrected vision disturbance
  • Vestibular problems
  • Major depression
  • Hallucinations or other psychiatric disturbances
  • Tachycardia
  • Bradycardia
  • Arrhythmias
  • Peptic ulcer disease
  • Use of anticholinergics
  • Use of cholinesterase inhibitors
  • Use of bladder antispasmodics
  • Use of tricyclic antidepressants

Treatment and study plan

Donepezil

Drug

Other names: Aricept

Primary outcomes

  1. Delta Medio-lateral Postural Sway Range (Foam)

    Time frame: Six weeks

    Increased body sway while standing may be markers for increased risk of falling in Parkinson's disease. Sway was measured with an inertial sensor attached to the waist. Participants did this task on a foam pad. We reported the delta in the donepezil and placebo phases [post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase].

  2. Delta of the Variability of Stride Time While Walking

    Time frame: Six weeks

    Variability in stride time time and an increase with dual tasking is another marker for increased fall risk in Parkinson's disease. Stride time variability was measured with inertial sensors attached to both feet. The delta for each phase is reported [post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase].

Secondary outcomes

  1. Short-latency Afferent Inhibition is a Marker of Cortical Cholinergic Activity

    Time frame: Six weeks

    Short-latency afferent inhibition (SAI) by a peripheral stimulation is a transcranial magnetic stimulation method to evaluate cortical cholinergic activity. Short-latency afferent Inhibition will be used to determine if our subjects with Parkinson's disease have evidence of reduced cholinergic tone which correlates with their measures of postural and gait instability. We report the SAI at the end of each phase (post-placebo phase and post-donepezil phase). SAI is reported in motor-evoked potential (MEP).

  2. Attention Network Test

    Time frame: Six weeks

    Attention Network Test (ANT) is 15 minute computerized test or reaction times with various cues and targets designed to assess alerting, orienting and executive control of attention. Deficits of attention are related to fall risk and may be affected by donepezil.

    The delta of the Orienting Network Efficiency is reported for each phase (pre- and post-donepezil phase and pre- and post-placebo phase).

    Details: In accordance with Fan et al. (2002), the subtraction method was applied to isolate the efficiency of the three attentional networks as follows: for the alerting network efficiency: mean RT NC trials - mean RT DC trials; for the orienting network efficiency: mean RT CC trials - mean RT SC trials; and for the executive network efficiency: mean RT I trials - mean RT C trials. For both the alerting and orienting effects, higher subtraction scores indicate greater efficiency; by contrast, the more efficient the executive network is, the lower the subtraction score.

Sponsors and collaborators

Lead sponsor

Oregon Health and Science University

Other

Collaborators

  • Michael J. Fox Foundation for Parkinson's Research

Registry information

Important dates

Study start
2014
Primary completion
2017
Study completion
2017
First posted
Aug 1, 2014
Registry last updated
Nov 14, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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