Parkinson Disease
Conditions
Brief summary
Parkinson's disease (PD) is a neurodegenerative disease that affects about 1% of the elderly population and accounts for substantial disability and health care costs. Disability is largely driven by mobility deficits caused by impaired gait. Effective treatments are available to restore lower limb function and improve gait, but response to treatment varies greatly from patient to patient and often shows only small effect sizes. Addressing this heterogeneity requires personalization, a concept referred to precision neurorehabilitation. StimuLOOP.PD intends to foster structured and reproducible methods for precision neurorehabilitation of gait in PD. The investigator will conduct a proof-of-concept study to investigate a combination of two methods that are each tailored to the individual patient. Two innovative technologies are applied in concert to enhance recovery of lower limb function. 1. Hyper-personalized feedback (HPF): For lower limb motor rehabilitation, the investigator will employ real-time continuous feedback for movement aspects that are specific to each participant's motor deficit. The feedback will be adapted and tailored to each participant. This results in a two-step personalization; in a first step, the investigator will choose what movement aspect is therapeutically targeted, and in a second step, the investigator will define how the feedback is presented to the participant. 2. Targeted auditory stimulation during sleep (TASS):The investigator aim to reactivate rehabilitation- related memories through the presentation of auditory stimuli during sleep with the goal of promoting motor memory consolidation into stable motor commands. The HPF intervention is expected to induce rapid adaptations, which however do not persist over multiple days. To counter this, the investigator will leverage memory reactivation during sleep to enhance the consolidation of the movement patterns that are learned during HPF. The investigator expect that these interventions will lead to greater gains in functional walking ability. Beyond demonstrating a proof-of-concept for novel methods of precision neurorehabilitation, positive results of this project may have implications for neurorehabilitation treatment in general by providing first insights into the benefits and interplay of HPF and TASS.
Interventions
For lower limb motor rehabilitation, the investigator will employ real-time continuous feedback for movement aspects that are specific to each participant's motor deficit. The feedback will be adapted and tailored to each participant.
The investigator aim to reactivate rehabilitation- related memories through the presentation of auditory stimuli during sleep with the goal of promoting motor memory consolidation into stable motor commands
Identical auditory presentation during the motor rehabilitation training, but not during the night (sham promotion memory reactivation)
Sponsors
ETH Zurich (Switzerland)
Cereneo AG
University Children's Hospital, Zurich
Lake Lucerne Institute AG
University of Zurich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Quadruple (participant, care provider, investigator, outcomes assessor).
Intervention model description
Consolidation Arm: hyper-personalized feedback based-motor rehabilitation with targeted auditory stimulation during sleep (HPF intervention, TASS intervention)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Idiopathic Parkinson's disease with gait and postural stability deficits * ≥18 years of age * United Parkinson Disease Rating Scale (UPDRS) III gait scores 1-3 * UPDRS III postural instability scores 1-3 * Prescribed rehabilitation therapy at cereneo * Informed consent as documented by signature * Adjustments in dopaminergic medication and deep brain stimulation (DBS) to improve motor symptoms implemented to the current best possible extent
Exclusion criteria
* Cognitive impairment, Montreal Cognitive Assessment (MoCa) \< 20 * Comprehensive aphasia precluding the understanding of study-related information * Other neurological or medical condition that caused sustained clinically relevant gait and/or postural stability deficits * Expected acute hospitalization during the training period * History of a physical or neurological condition that interferes with study procedures * Social and/or personal circumstances that interfere with the ability to return for therapy sessions and follow-up assessments * Not capable of voluntary gait adaptation * Patients taking benzodiazepines or Z-drugs that have a significant effect on sleep EEG * Recent DBS implant (≤ 6 months) * Inability to perform outcome assessments without walking aid * Skin disorders/problems/allergies in face/ear area that could worsen with electrode application (e.g. nickel allergy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6 min walking test | Pre, immediately post motor rehabilitation and 1 month post motor rehabilitation | Change in functional walking ability assessed with the 6 min walking test |
| MiniBEST test | Pre, immediately post motor rehabilitation and 1 month post motor rehabilitation | the change in postural stability assessed with the MiniBEST test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase Coordination Index | Pre, immediately post motor rehabilitation training and during 15 days of motor rehabilitation training and one-month post-training | Motor learning assessed via changes in coordination. Coordination assessed using the Phase Coordination Index. |
| Continuous Relative Phase | Pre, immediately post motor rehabilitation training and during 15 days of motor rehabilitation training and one-month post-training | Motor learning assessed via changes in coordination. Coordination assessed using Continous Relative Phase. |
| Variability | Pre, immediately post motor rehabilitation training and during 15 days of motor rehabilitation training and one-month post-training | Motor learning assessed via changes in variability. Variability assessed using the coefficient of variation (%CV) of common spatio-temporal gait parameters, including stride time, stride length, step length, swing time, stance time, step width, and double limb support time. |
| Symmetry | Pre, immediately post motor rehabilitation training and during 15 days of motor rehabilitation training and one-month post-training | Motor learning assessed via changes in symmetry. Symmetry (%) in step length and step time. |
| Margin of Stability | Pre, immediately post motor rehabilitation training and during 15 days of motor rehabilitation training and one-month post-training | Motor learning assessed via changes in stability. Stability assessed using Margin of Stability. |
| Resilience | Pre, immediately post motor rehabilitation training and during 15 days of motor rehabilitation training and one-month post-training | Motor learning assessed via changes in stability: Stability assessed using resilience metrics. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Event related spectral perturbation (ERSP) | During 15 days of motor rehabilitation training | ERSP: \[µV\^2/Hz or % or dB of baseline if normalized over time\] and event-related potential (ERP) \[µV over time\] locked to stimuli from frontal, single-channel EEG signal |
| Frequency spectrum | During 15 days of motor rehabilitation training | Single-channel sleep EEG: \[µV\^2/Hz\] from frontal, single-channel EEG signal |
| Slow-wave activity | During 15 days of motor rehabilitation training | Single-channel sleep EEG: \[µV\^2/Hz or % or dB of baseline if normalized\] in scored non-rapid eye movement (NREM) sleep from frontal, single-channel EEG signal |
| Sigma power | During 15 days of motor rehabilitation training | Single-channel sleep EEG: \[µV\^2/Hz or % or dB of baseline if normalized\] in scored NREM sleep from frontal, single-channel EEG signal |
| Quantity | During 15 days of motor rehabilitation training | Single-channel sleep EEG: density \[number/min\], and characteristics (amplitude, peak frequency, bandwidth) of sleep oscillations (spindles, K-complexes, slow-wave-spindle-coupling) in scored NREM sleep from frontal, single-channel EEG signal. |
| Quality of Life (EQ-5D-5L) | Pre motor rehabilitation training and 1 month after training | Patient-Reported Outcomes (PRO) measurement that can assess patients' quality of life, irrespective of the disease. Quality of life scale developed by EuroQol Group called EQ-5D-5L, scoring from level 1 indicating no problem to level 5 indicating extreme problems. |
| Standard sleep architecture measures | During 15 days of motor rehabilitation training | Single-channel sleep Electroencephalography (EEG): (e.g. % N3, % N2, wake after sleep onset, Sleep efficiency) from scored EEG, electromyography (EMG), and electrooculography (EOG) signal (note: bandpass filtered EMG and EOG signal will only be used for offline sleep scoring according to American Academy of Sleep Medicine standards) |
Countries
Switzerland
Outcome results
None listed