Improving Walking Automaticity in Parkinson's Disease: Levodopa or Donepezil

NCT03599726 | Completed Early Phase 1 FDA Drug

• 1 other identifier: eIRB 17805
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Safe and independent mobility at home and in the community requires control of walking while accomplishing other functional tasks. A hallmark of healthy control of walking is automaticity, defined as the ability of the nervous system to successfully coordinate movement with minimal use of attention-demanding executive resources \[1\]. Recent evidence indicates that walking disorders are often characterized by a shift in the locomotor control strategy from healthy automaticity to compensatory executive control. This shift is potentially detrimental to walking performance as an executive control strategy is not optimized for locomotor control and it places excessive demands on a limited pool of cognitive reserve. Here, the investigators hypothesize that walking automaticity, as measured by the prefrontal cortex activity while walking, will be improved by donepezil (a cholinesterase inhibitor).

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (1)

• Oxygenated Hemoglobin levels in the prefrontal cortex while walking (microM).

  Oxygenated hemoglobin changes during walking, compared to standing, will be quantified with a wireless functional near infrared spectroscopy (fNIRS). Subjects with PD will be tested while walking after 14 days of placebo and their regular dose of levodopa or after 14 days of donepezil (5 mg/day oral) and their regular dose of levodopa, with a two week wash out in between.

  43 days

Secondary Outcomes (5)

• Stride time variability of gait (%).

  43 days

• Gait speed (m/s)

  43 days

• Stride length (m)

  43 days

• Turning velocity (degrees/s)

  43 days

• Turning duration (s)

  43 days

Study Arms (2)

Active study drug: Donepezil

EXPERIMENTAL

Donepezil 5 mg per day for week 1-2 or 5-6

Drug: Donepezil

Placebo study drug: Placebo

PLACEBO COMPARATOR

Placebo 5 mg per day for week 1-2 or 5-6

Drug: Placebo

Interventions

Donepezil DRUG

Donepezil 5 mg per day for week 1-2 or 5-6

Also known as: Aricept

Active study drug: Donepezil

Placebo DRUG

Placebo 5 mg per day for week 1-2 or 5-6

Placebo study drug: Placebo

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be able to stand unassisted for a minute and to walk continuously for 2 minutes without assistance or assistive devices.
• Diagnosis of idiopathic Parkinson's disease with sensitivity to levodopa and off-medication Hoehn \& Yahr scores of III-IV.
• Subjects must be currently taking levodopa, and not already taking donepezil
• The subjects must be able to appreciate the purpose of the research, give informed consent to participate, be able to cooperate with the testing and be compliant with taking the experimental medications.

You may not qualify if:

• Use of anticholinergics for parkinsonism, cholinesterase inhibitors for cognitive problems, bladder antispasmodics for urinary urgency or tricyclic antidepressants for depression are contraindications.

Sponsors & Collaborators

• Oregon Health and Science University: lead
• Medical Research Foundation, Oregon: collaborator

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

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

Study Officials

• Martina Mancini, PhD

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant professor of Neurology, co-director of the Balance Disorders Laboratory, Principal Investigator

Study Record Dates

• First Submitted: June 29, 2018
• First Posted: July 26, 2018
• Study Start: July 30, 2018
• Primary Completion: May 30, 2019
• Study Completion: July 30, 2019
• Last Updated: May 11, 2020

Record last verified: 2020-05

Locations

US (1)