Effects of Cholinergic Augmentation on Measures of Balance and Gait

NCT02206620 | Completed Phase 2 Results

• 1 other identifier: 9437
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (2)

• Delta Medio-lateral Postural Sway Range (Foam)

  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 \[post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase\].

  Six weeks

• Delta of the Variability of Stride Time While Walking

  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 \[post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase\].

  Six weeks

Secondary Outcomes (2)

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

  Six weeks

• Attention Network Test

  Six weeks

Study Arms (2)

Donepezil

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Donepezil DRUG

Also known as: Aricept

Donepezil; Placebo

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Oregon Health and Science University: lead
• Michael J. Fox Foundation for Parkinson's Research: collaborator

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239-3098, United States

Location

Related Publications (1)

• 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.

  PMID: 26697847 DERIVED

Related Links

• The Michael J. Fox Foundation "Fox Trial Finder" Study Listing

MeSH Terms

Conditions

Parkinson Disease

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Martina Mancini
• Organization: Oregon Health & Science University

mancinim@ohsu.edu

5034182602

Study Officials

• John Nutt, M.D.

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: July 29, 2014
• First Posted: August 1, 2014
• Study Start: July 1, 2014
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: November 14, 2019
• Results First Posted: November 14, 2019

Record last verified: 2019-11

Locations

US (1)