Neurobiological Drivers of Mobility Resilience: The Dopaminergic System

NCT04325503 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: HUM001564905U01AG061393-05
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Walking with age becomes both slower and less 'automated', requiring more attention and brain resources. As a result, older adults have a greater risk of negative outcomes and falls. There is an urgent need to identify factors that can help compensate for these harmful factors and reduce walking impairments, as there are currently no effective treatments available. Investigators have recently discovered that \~20% of older adults maintain fast walking speed even in the presence of small blood vessel brain changes and leg problems, thus appearing to be protected against these harmful factors. The investigators work suggests that the brain dopamine (DA) system may be a source of this protective capacity. Investigators have also shown that lower levels of dopamine are associated with slow walking. Investigators will be investigating the role of dopamine on slow walking and other parkinsonian signs using detailed clinical assessment, assessment of dopamine activity, and clinical interventions.

Conditions

Parkinsonian Signs in Older Persons

Keywords

slow gait; Parkinsonian signs

Outcome Measures

Primary Outcomes (6)

• Average Gait Speed

  Average gait speed as measured using wearable sensors worn during walking tasks. Gait speed is measured in meters per second.

  7-13 days after beginning treatment.

• Montreal Cognitive Assessment (MoCA)

  Cognitive assessment used to evaluate individuals for mild cognitive impairment. Scores range from 0-30. Higher scores indicate better performance.

  7-13 days after beginning treatment

• Mini Balance Evaluation Systems Test (Mini-BESTest)

  The mini-BESTest is a 14-item evaluation of dynamic balance and postural control. It is scored from 0-28, with higher scores indicating better performance.

  7-13 days after beginning treatment

• Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total

  MDS-UPDRS part III is the motor examination portion of the UPDRS evaluation. Scores range from 0-132, with higher scores indicating greater severity of motor symptoms.

  7-13 days after beginning treatment

• Cognitive Z-score

  Composite variable calculated based on the Stroop Color Word Interference test I-IV (assessment of attention) and Delis-Kaplan Executive Function System Trail Making test I-V (assessment of executive function and working memory), adjusted based on normative data for older adults. A z-score of 0 represents the control population mean. Scores above the mean indicate better performance, while scores below the mean indicate poorer performance.

  7-13 days after beginning treatment

• Wechsler Adult Intelligence System Digit Symbol Substitution Test

  Evaluation of cognitive functioning in which a participant is given a key of numbers 1-9, each paired with a unique symbol. Below the key, is a series of random numbers which they participant must fill in the corresponding symbol for. They have 120 seconds to complete the task. Participants receive one point for each correct symbol written. Score range from 0-133.

  7-13 days after beginning treatment

Secondary Outcomes (1)

• Short Activities-specific Balance Confidence Scale Score

  7-13 days after beginning treatment

Study Arms (1)

Treatment

EXPERIMENTAL

carbidopa and carbidopa-levodopa treatment for parkinsonian signs in older persons using standard dosing, frequency for a duration for 1-2 weeks

Drug: carbidopa

Interventions

carbidopa DRUG

carbidopa and carbidopa-levodopa standard treatment

Also known as: carbidopa-levodopa

Treatment

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 60 or older (M/F)
• Evidence of mild parkinsonian signs (incl. slow gait (\< 1m/s))

You may not qualify if:

• Presence of clinically significant degenerative joint disease and/or neuropathy interfering with proper assessment of the motor UPDRS exam.
• Presence of significant dementia.
• Evidence of a large vessel stroke in a clinically relevant area (cerebral cortex, basal ganglia, thalamus) or mass lesion on structural brain imaging (MRI).
• Participants in whom magnetic resonance imaging (MRI) is contraindicated including, but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord, or cochlear implant.
• Severe claustrophobia precluding neuroimaging procedures.
• Hypersensitivity to the carbidopa, levodopa, and tablet components.
• Any other medical history determined by investigators to preclude safe participation.

Sponsors & Collaborators

• University of Michigan: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Functional Neuroimaging, Cognitive, and Mobility Lab, University of Michigan

Ann Arbor, Michigan, 48105, United States

Location

MeSH Terms

Interventions

Carbidopa; carbidopa, levodopa drug combination

Intervention Hierarchy (Ancestors)

Methyldopa; Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Hydrazines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Nicolaas Bohnen
• Organization: Unversity of Michigan

nbohnen@umich.edu

734-998-8400

Study Officials

• Nicolaas Bohnen, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 24, 2020
• First Posted: March 27, 2020
• Study Start: February 8, 2021
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: April 4, 2024
• Results First Posted: September 28, 2023

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)