Clinical trial NCT02206620: Effects of Cholinergic Augmentation on Measures of Balance and Gait
Official title: Effects of Cholinergic Augmentation on Measures of Balance and Gait
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson's Disease
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: Michael J. Fox Foundation for Parkinson's Research
First posted: 2014-08-01
Enrollment: 49
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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
* Use of cholinesterase inhibitors
* Use of bladder antispasmodics
* Use of tricyclic antidepressants

Primary outcomes:
measure: Delta Medio-lateral Postural Sway Range (Foam)
timeFrame: Six weeks
measure: Delta of the Variability of Stride Time While Walking
timeFrame: Six weeks
Secondary outcomes:
measure: Short-latency Afferent Inhibition is a Marker of Cortical Cholinergic Activity
timeFrame: Six weeks
measure: Attention Network Test
timeFrame: Six weeks
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: John Nutt, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mancini M, Fling BW, Gendreau A, Lapidus J, Horak FB, Chung K, Nutt JG. Effect of augmenting cholinergic function on gait and balance. BMC Neurol. 2015 Dec 23;15:264. doi: 10.1186/s12883-015-0523-x.