Neurobiological Drivers of Mobility Resilience: The Dopaminergic System - Placebo-Controlled Arm

NCT06219915 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: HUM00156490-A5U01AG061393-05
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

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 in this double-blinded, placebo-controlled study 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 (1)

• Average Gait Speed

  Average gait speed as measured using wearable sensors and while walking on a sensor mat. Measured in meters per second.

  Baseline and post-intervention (7-13 days after beginning supplement)

Secondary Outcomes (3)

• Parkinson's Disease (PD)-Cognitive Rating Scale Score

  Baseline and post-intervention (7-13 days after beginning supplement)

• Mean of Number of Incorrect Responses on the Stroop Color Word Stepping Test

  Baseline and post-intervention (7-13 days after beginning supplement)

• Mean of Reaction Time During the Stroop Color Word Stepping Test

  Baseline and post-intervention (7-13 days after beginning supplement)

Study Arms (2)

Carbidopa Monotherapy and Carbidopa-Levodopa

EXPERIMENTAL

Participants will begin by taking 25mg of Carbidopa monotherapy three times per day (TID) for 3 days. On day four, participants will begin taking 1 tablet of Carbidopa-Levodopa (25/100mg) TID in addition to the Carbidopa monotherapy. On day seven, participants will increase to 1.5 tablets of Carbidopa-Levodopa (25/100mg) TID while maintaining 25mg Carbidopa monotherapy TID. The intervention will end after ten days of supplementation.

Drug: Carbidopa 25 mg; Drug: Carbidopa-Levodopa 25/100 mg

Placebo

PLACEBO COMPARATOR

Participants will begin by taking a 25mg placebo tablet three times per day (TID) for 3 days. On day four, participants will begin taking a separate placebo tablet TID in addition to the original placebo. On day seven, participants will increase to 1.5 tablets of the second placebo TID while maintaining 25mg original placebo TID. The intervention will end after ten days of supplementation.

Drug: Placebo 1; Drug: Placebo 2

Interventions

Carbidopa 25 mg DRUG

Participants will take one 25mg Carbidopa tablet 3 times a day for 10 days.

Carbidopa Monotherapy and Carbidopa-Levodopa

Carbidopa-Levodopa 25/100 mg DRUG

Participants will take one 25/100mg carbidopa-levodopa tablet 3 times a day on days 4-6, then increase to 1.5 tablets 3 times a day on days 7-10.

Also known as: Sinemet

Carbidopa Monotherapy and Carbidopa-Levodopa

Placebo 1 DRUG

Participants will take one 25mg placebo tablet 3 times a day for 10 days.

Placebo

Placebo 2 DRUG

Participants will take one 100mg placebo tablet 3 times a day on days 4-6, then increase to 1.5 tablets 3 times a day on days 7-10.

Placebo

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:

• Evidence of prior established diagnosis and/or treatment for PD.
• Presence of clinically significant degenerative joint disease and/or neuropathy interfering with proper assessment of the motor exam.
• Presence of significant dementia.
• History of stroke with residual clinical deficit interfering with walking.
• For optional MR imaging only: 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.
• For optional brain imaging only: Severe claustrophobia precluding neuroimaging procedures.
• Participants that have been on monoamine oxidase inhibitors (MAOIs) within 2 weeks prior to starting study.
• Inability to stand or walk without an assistive device
• Hypersensitivity to the carbidopa, levodopa, and tablet components.
• History of myocardial infarction (MI) with residual arterial, nodal or ventricular arrhythmia
• History of peptic ulcer
• Chronic wide angle glaucoma
• Narrow angle glaucoma
• Major psychotic disorder
• Severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease

Sponsors & Collaborators

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

Study Sites (2)

Domino's Farms

Ann Arbor, Michigan, 48105, United States

Location

University Hospital

Ann Arbor, Michigan, 48109, 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: Principle Investigator
• Organization: University of Michigan

pchatkae@umich.edu

734-998-8400

Study Officials

• Chatkaew Pongmala, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Investigator

Study Record Dates

• First Submitted: January 12, 2024
• First Posted: January 23, 2024
• Study Start: March 15, 2024
• Primary Completion: May 30, 2024
• Study Completion: May 30, 2024
• Last Updated: June 17, 2025
• Results First Posted: June 17, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)