Clinical trial NCT03840837: Cholinergic Neurotransmission in Mobility and Cognition in Parkinson Disease
Official title: Cholinergic Neurotransmission - A Common Underlying Mechanism of Cognitive and Gait Impairment in Parkinson Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Parkinson Disease
Parkinson Disease Dementia
Keywords: cognitive impairment
Parkinson disease dementia
wearable sensor
gait analysis
rivastigmine
cholinesterase inhibitor
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2019-02-15
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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).
Primary purpose: TREATMENT

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.

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).

Eligibility 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).

Primary outcomes:
measure: Timed-Up-and-Go (TUG) duration [s]
timeFrame: Data analysis will be completed within 6 months of completing study enrollment.
measure: NeuroTrax Executive Function score
timeFrame: Data analysis will be completed within 6 months of completing study enrollment.
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland School of Medicine, Dept. of Neurology
state: Maryland
Study officials:
affiliation: University of Maryland, Baltimore
name: Rainer von Coelln, Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: