Effects of Cholinergic Augmentation on Measures of Balance and Gait
Overview
- Phase
- Phase 2
- Intervention
- Donepezil
- Conditions
- Parkinson's Disease
- Sponsor
- Oregon Health and Science University
- Enrollment
- 49
- Locations
- 1
- Primary Endpoint
- Delta of the Variability of Stride Time While Walking
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
John G. Nutt
M.D.
Oregon Health and Science University
Eligibility 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
Arms & Interventions
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.
Intervention: Donepezil
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.
Intervention: Donepezil
Outcomes
Primary Outcomes
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 \[post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase\].
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 \[post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase\].
Secondary Outcomes
- Short-latency Afferent Inhibition is a Marker of Cortical Cholinergic Activity(Six weeks)
- Attention Network Test(Six weeks)