Cholinergic Neurotransmission in Mobility and Cognition in Parkinson Disease

• ClinicalTrials.gov Identifier: NCT03840837
• Recruitment Status: Completed
• First Posted: February 15, 2019
• Last Update Posted: January 31, 2022
• Sponsor: University of Maryland, Baltimore
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): F. Rainer von Coelln, MD, University of Maryland, Baltimore

Study Description

Brief Summary:

This is a single-site non-randomized open label pilot study. The investigators will use accelerometer-based instrumented gait analysis and computerized cognitive testing to study the interaction of motor and cognitive dysfunction in Parkinson disease dementia (PDD), and the effect of rivastigmine on motor and cognitive performance. All study participants will be tested for motor and cognitive performance at baseline (arm 1). A subgroup of study participants will then be treated with rivastigmine for 12 weeks (arm 2), and the effect of this treatment on gait measures and cognitive measures will be analyzed at the follow-up visit 12 weeks after the baseline visit. Specifically, we will determine which components of motor and cognitive impairment are associated with each other, and which components of the two domains respond to rivastigmine-mediated stimulation of cholinergic neurotransmission.

Condition or disease	Intervention/treatment	Phase
Parkinson Disease; Parkinson Disease Dementia	Drug: Rivastigmine transdermal patch	Phase 4

Detailed Description:

This is a single-site non-randomized open label clinical trial in patients with Parkinson disease (PD) and mild to moderate cognitive deficits, designed to 1) identify associations between cognitive impairment and gait impairment, and 2) identify cognitive domains and gait measures that improve after 12 weeks of treatment with rivastigmine. Aim 1 will be addressed with a cross-sectional approach (arm 1, baseline only, all participants), and aim 2 will be addressed with a longitudinal interventional approach (arm 2, 12 week-treatment with rivastigmine, subgroup of participants).

Patients with idiopathic Parkinson disease (PD) and mild to moderate cognitive deficits amounting to PD dementia (PDD) will be enrolled. At baseline (arm 1), all participants will perform the timed-up-and-go test (TUG), wearing a light-weight sensor device strapped to the lower back with a neoprene belt. Participants will also complete a computerized cognitive test battery (NeuroTrax Mild Cognitive Impairment & Early Dementia Battery by MindStreams). A subgroup of participants (arm 2) will then be treated with transdermal rivastigmine for 12 weeks, with dose increases every 4 weeks and titration up to 13.3 mg/24h, if tolerated. The same assessment (quantitative gait testing and NeuroTrax computerized cognitive test battery) will be repeated after 12 weeks, with the participant on a stable dose of transdermal rivastigmine.

The investigators will analyze correlation of iTUG measures and cognitive measures at baseline (cross-sectional analysis). The investigators will also analyze change in iTUG measures and cognitive measures between baseline and follow-up for the subgroup of participants in arm 2 (in other words, before and after rivastigmine treatment; longitudinal analysis).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: All participants perform a baseline assessment (arm 1 - cross-sectional). A subgroup of participants (based on physician and participant choice) proceed to a 12-week treatment phase with the study drug (transdermal rivastigmine) and subsequent follow-up assessment (arm 2 - longitudinal).
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Cholinergic Neurotransmission - A Common Underlying Mechanism of Cognitive and Gait Impairment in Parkinson Disease
• Actual Study Start Date: May 2, 2019
• Actual Primary Completion Date: April 1, 2020
• Actual Study Completion Date: April 1, 2020

Arms and Interventions

Arm	Intervention/treatment
No Intervention: Arm 1: baseline only (cross-sectional); At baseline, all participants will undergo instrumented gait/balance testing, using a wearable sensor (Dynaport MT), and cognitive testing, using a computerized cognitive test battery (NeuroTrax Mild Cognitive Impairment & Early Dementia Battery by MindStreams). In other words, all participants will be part of arm 1.
Experimental: Arm 2: rivastigmine (longitudinal); As study intervention, a subgroup of participants will then be treated with transdermal rivastigmine patch for 12 weeks, with dose increases every 4 weeks and titration up to 13.3 mg/24h, if tolerated. For the arm 2 subgroup of participants, the same assessment that was performed at baseline (quantitative gait testing and NeuroTrax computerized cognitive test battery) will be repeated after 12 weeks, with the patient on a stable dose of transdermal rivastigmine.	Drug: Rivastigmine transdermal patch; Titration of transdermal rivastigmine, as per arm description.; Other Name: Exelon transdermal patch

Outcome Measures

Primary Outcome Measures :

1. Timed-Up-and-Go (TUG) duration [s] [ Time Frame: Data analysis will be completed within 6 months of completing study enrollment. ]
   Time participant needs to complete the TUG.
2. NeuroTrax Executive Function score [ Time Frame: Data analysis will be completed within 6 months of completing study enrollment. ]
   Result of the NeuroTrax computerized cognitive test of executive function.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age ≥ 18 years.
• Diagnosis of idiopathic Parkinson disease.
• Mild to moderate cognitive impairment, as determined by a MoCA score of ≤ 25 and ≥ 10.
• Patient passes the Evaluation to Sign Consent (ESC) or a legally authorized representative (LAR) is present at the time of enrollment and signs the informed consent form on behalf of the patient.
• Patient is enrolled (or willing to be enrolled) in the University of Maryland Parkinson Disease and Movement Disorders Center PD Research Database (HP 42195)

Exclusion Criteria:

• Advanced Parkinson disease (Hoehn & Yahr stage 5), with inability to walk unassisted.
• Other medical condition(s) that significantly interfere(s) with gait and balance (e.g., advanced arthritis).

Contacts and Locations

Locations

United States, Maryland

University of Maryland School of Medicine, Dept. of Neurology

Baltimore, Maryland, United States, 21201

Sponsors and Collaborators

University of Maryland, Baltimore

National Institute on Aging (NIA)

Investigators

• Principal Investigator: Rainer von Coelln, Dr. med.; University of Maryland School of Medicine

More Information

• Responsible Party: F. Rainer von Coelln, MD, Assistant Professor, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT03840837
• Other Study ID Numbers: HP-00084074; 3P30AG028747-13S3 ( U.S. NIH Grant/Contract )
• First Posted: February 15, 2019
• Last Update Posted: January 31, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Plan Description

All data generated during this project will be shared with the scientific community through peer-reviewed publications and presentations at national and international conferences.

We will share our raw data with qualified collaborating scientists upon request. Only aggregated data of study participants will be made available to other researchers.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by F. Rainer von Coelln, MD, University of Maryland, Baltimore:

cognitive impairment; Parkinson disease dementia; wearable sensor; gait analysis; rivastigmine; cholinesterase inhibitor

Additional relevant MeSH terms:

Parkinson Disease; Dementia; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Rivastigmine; Cholinesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Neuroprotective Agents; Protective Agents