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

Stroke is the most common neurological disease in 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.S intends to foster structured and reproducible methods for precision neurorehabilitation of gait in stroke. The investigator will carry out a proof-of-concept study to investigate the integration of two personalized methods for each patient. Two innovative technologies are applied in concert to enhance the 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 the first step, the investigator will choose what movement aspect is therapeutically targeted, and in the second step, the investigator will define the feedback 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: Stroke
• 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: Yannik Rottenberger; Phone Number: +41 44 255 55 11; Email: yannik.rottenberger@usz.ch

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Ischemic stroke or intracerebral hemorrhage with a gait deficit older than 30 days but not more than 6 months.
• Functional Ambulation Category ≥3
• ≥18 years of age
• Informed consent as documented by signature

Exclusion Criteria:

• Cognitive impairment, Montreal Cognitive Assessment (MoCa) < 20
• Comprehensive aphasia precluding the understanding of study-related information
• Previous stroke that caused sustained clinically relevant cognitive, visual and/or gait 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
• Allergy to nickel
• Patients taking benzodiazepines or Z-drugs with a significant effect on sleep EEG

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
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)
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 min walking test (6MWT)	Change in functional walking ability assessed with the 6 min walking test (6MWT)	Pre, immediately post motor rehabilitation training and one-month post-training

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gait kinematics	Motor learning assessed via changes in gait kinematics: variability, symmetry, coordination, stability.	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
Single-channel sleep EEG (Electroencephalography)+ EMG (Electroencephalography) + EOG (Electrooculography)	Single-channel sleep EEG (Electroencephalography): sleep architecture, ERSP, ERP, frequency spectrum, slow-wave activity changes, changes in the spindle band, sleep oscillation detection (K-complexes, spindles, slow-wave-spindle-coupling) EMG ( Electromyography): signal from the chin recorded during sleep will be filtered between 10 and 100 Hz and re-referenced bilaterally according to AASM criteria and used for offline sleep staging EOG (Electrooculography): filtered between 0.3 and 35 Hz and used for offline sleep staging. EOG and EMG are only used for sleep scoring	During 15 days of motor rehabilitation training
Sleep hdEEG + EMG + EOG	Sleep high density EEG: sleep architecture, slow-wave activity topography, spindle band topography, ERSP, ERP, frequency spectrum, sleep oscillation detection (K-complexes, spindles, slow-wave-spindle-coupling). EOG (Electrooculography)and EMG ( Electromyography) are only used for sleep scoring	Pre motor rehabilitation training
Wake hdEEG	Wake high density EEG: theta topography, alpha topography, frequency spectrum at resting state, ERP in oddball task, ERSP in oddball task, characterization of wake slow waves if detectable	Pre and immediately post motor rehabilitation training
Quality of Life (EQ-5D-5L)	Patient-Reported Outcomes (PRO) measurement that can assess patients' quality of life, irrespective of the disease.	Pre motor rehabilitation training and 1 month after training

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: University Children's Hospital, Zurich; Cereneo AG; ETH Zurich (Switzerland); Vontobel-Stiftung

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 11, 2024
• First Submitted That Met QC Criteria: June 13, 2024
• First Posted (Actual): June 20, 2024

Study Record Updates

• Last Update Posted (Actual): June 20, 2024
• Last Update Submitted That Met QC Criteria: June 13, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 2022-01194

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