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Effects of Cholinergic Augmentation on Measures of Balance and Gait

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ClinicalTrials.gov Identifier: NCT02206620
Recruitment Status : Completed
First Posted : August 1, 2014
Results First Posted : November 14, 2019
Last Update Posted : November 14, 2019
Sponsor:
Collaborator:
Michael J. Fox Foundation for Parkinson's Research
Information provided by (Responsible Party):
John G. Nutt, Oregon Health and Science University

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Parkinson's Disease Drug: Donepezil Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Cholinergic Augmentation on Measures of Balance and Gait
Actual Study Start Date : July 2014
Actual Primary Completion Date : July 2017
Actual Study Completion Date : July 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Donepezil
Donepezil 5 mg per day for week 1-3 or 12-14. 10 mg/day for weeks 4-6 or 14-18, if tolerated.
Drug: Donepezil
Other Name: Aricept

Placebo Comparator: Placebo
Placebo 5 mg per day for week 1-3 or 12-14. 10 mg/day for weeks 4-6 or 14-18, if tolerated.
Drug: Donepezil
Other Name: Aricept




Primary Outcome Measures :
  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 Outcome Measures :
  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.




Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02206620


Locations
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United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239-3098
Sponsors and Collaborators
Oregon Health and Science University
Michael J. Fox Foundation for Parkinson's Research
Investigators
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Principal Investigator: John Nutt, M.D. Oregon Health and Science University
  Study Documents (Full-Text)

Documents provided by John G. Nutt, Oregon Health and Science University:

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: John G. Nutt, M.D., Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT02206620    
Other Study ID Numbers: 9437
First Posted: August 1, 2014    Key Record Dates
Results First Posted: November 14, 2019
Last Update Posted: November 14, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Donepezil
Cholinergic Agents
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents