Precision Sensorimotor Neurorehabilitation Through Personalized Stimulation Loops (StimuLOOP-PD)

Precision Sensorimotor Neurorehabilitation Through Personalized Stimulation Loops in a Proof-of-principle Study

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.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Behavioral: Hyper-personalized feedback (HPF intervention); Behavioral: Control targeted auditory stimulation during sleep (TASS sham intervention); Behavioral: Targeted auditory stimulation during sleep (TASS verum intervention)

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Zurich
    • Zürich, Zurich, Switzerland, 8091
      • Recruiting
      • University Hospital Zurich
      • Contact: Angelina Maric; Phone Number: +41 44 255 86 15; Email: Angelina.Maric@usz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Consolidation arm; Hyper-personalized feedback-based motor rehabilitation with targeted auditory stimulation during sleep (HPF intervention, TASS verum intervention)	Behavioral: Hyper-personalized feedback (HPF intervention); 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.; Behavioral: Targeted auditory stimulation during sleep (TASS verum intervention); 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
Sham Comparator: Adaptation Arm; Hyper-personalized feedback-based motor rehabilitation with sham targeted auditory stimulation during sleep (HPF intervention, TASS sham intervention)	Behavioral: Hyper-personalized feedback (HPF intervention); 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.; Behavioral: Control targeted auditory stimulation during sleep (TASS sham intervention); Identical auditory presentation during the motor rehabilitation training, but not during the night (sham promotion memory reactivation)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 min walking test	Change in functional walking ability assessed with the 6 min walking test	Pre, immediately post motor rehabilitation and 1 month post motor rehabilitation
MiniBEST test	the change in postural stability assessed with the MiniBEST test	Pre, immediately post motor rehabilitation and 1 month post motor rehabilitation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Coordination Index	Motor learning assessed via changes in coordination. Coordination assessed using the Phase Coordination Index.	Pre, immediately post motor rehabilitation training and during 15 days of motor rehabilitation training and one-month post-training
Continuous Relative Phase	Motor learning assessed via changes in coordination. Coordination assessed using Continous Relative Phase.	Pre, immediately post motor rehabilitation training and during 15 days of motor rehabilitation training and one-month post-training
Variability	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.	Pre, immediately post motor rehabilitation training and during 15 days of motor rehabilitation training and one-month post-training
Symmetry	Motor learning assessed via changes in symmetry. Symmetry (%) in step length and step time.	Pre, immediately post motor rehabilitation training and during 15 days of motor rehabilitation training and one-month post-training
Margin of Stability	Motor learning assessed via changes in stability. Stability assessed using Margin of Stability.	Pre, immediately post motor rehabilitation training and during 15 days of motor rehabilitation training and one-month post-training
Resilience	Motor learning assessed via changes in stability: Stability assessed using resilience metrics.	Pre, immediately post motor rehabilitation training and during 15 days of motor rehabilitation training and one-month post-training

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life (EQ-5D-5L)	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.	Pre motor rehabilitation training and 1 month after training
Standard sleep architecture measures	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)	During 15 days of motor rehabilitation training
Event related spectral perturbation (ERSP)	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	During 15 days of motor rehabilitation training
Frequency spectrum	Single-channel sleep EEG: [µV^2/Hz] from frontal, single-channel EEG signal	During 15 days of motor rehabilitation training
Slow-wave activity	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	During 15 days of motor rehabilitation training
Sigma power	Single-channel sleep EEG: [µV^2/Hz or % or dB of baseline if normalized] in scored NREM sleep from frontal, single-channel EEG signal	During 15 days of motor rehabilitation training
Quantity	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.	During 15 days of motor rehabilitation training

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: University Children's Hospital, Zurich; Cereneo AG; ETH Zurich (Switzerland); Lake Lucerne Institute AG

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: August 9, 2024
• First Submitted That Met QC Criteria: September 19, 2024
• First Posted (Actual): September 23, 2024

Study Record Updates

• Last Update Posted (Actual): October 1, 2024
• Last Update Submitted That Met QC Criteria: September 27, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 2023-01400

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No