Personalized Stimulation Loop for Neurorehabilitation in Parkinson: a Proof-of-principle Study

Overview

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-Sleep intends to foster structured and reproducible methods for precision neurorehabilitation of gait in PD. The investigators will conduct a proof-of-concept study to investigate a sleep intervention tailored to the individual patient in the context of motor rehabilitation. • Targeted auditory stimulation during sleep (TASS): The investigators aim to reactive rehabilitation-related memories through presentation of auditory stimuli during sleep with the goal of promoting motor memory consolidation into stable motor commands. The investigators will leverage TASS to enhance consolidation of the movement patterns that are learned during rehabilitation. The investigators expect that this intervention will lead to greater gains in functional walking ability and balance. Beyond demonstrating a proof-of-concept for novel methods of applying TASS stimulation in the context of neurorehabilitation, positive results of this project may have implications for neurorehabilitation treatment in general by providing first insights into the benefits and interplay of TASS with a rehabilitation.

Interventions

• Other TASS Intervention (Sham)
  Participants will sleep with the portable EEG (TSB, Axo, Tosoo AG, Zurich, CH) during 15 days of their regular motor rehabilitation. No auditory stimuli will be delivered.
• Other TASS Intervention (Verum)
  TASS: Participants will sleep with the portable EEG (TSB, Axo, Tosoo AG, Zurich, CH) during 15 days of their regular motor rehabilitation. Auditory stimuli will be delivered through the integrated headphones when non-rapid-eye-movement (NREM) sleep is detected during the night to induce TASS.

Primary outcome measures

• functional walking ability [Time frame: Baseline, one to three days after the last intervention day (post-assessment), one month after the last intervention day (follow-up assessment).]
• postural stability [Time frame: Baseline, one to three days after the last intervention day (post-assessment), one month after the last intervention day (follow-up assessment).]

Secondary outcome measures (5)

• Phase Coordination Index [Time frame: Baseline, one to three days after the last intervention day (post-assessment), one month after the last intervention day (follow-up assessment).]
• Continuous Relative Phase [Time frame: Baseline, one to three days after the last intervention day (post-assessment), one month after the last intervention day (follow-up assessment).]
• Variability [Time frame: Baseline, one to three days after the last intervention day (post-assessment), one month after the last intervention day (follow-up assessment).]
• Symmetry [Time frame: Baseline, one to three days after the last intervention day (post-assessment), one month after the last intervention day (follow-up assessment).]
• Margin of Stability [Time frame: Baseline, one to three days after the last intervention day (post-assessment), one month after the last intervention day (follow-up assessment).]

Eligibility criteria

Inclusion criteria

• Idiopathic Parkinson's disease with gait and postural stability deficits
• ≥18 years of age
• UPDRS III gait scores 1-3
• UPDRS III postural instability scores 1-3
• Prescribed rehabilitation therapy
• Informed consent as documented by signature
• Adjustments in dopaminergic medication and DBS stimulation to improve

Exclusion criteria

• Cognitive impairment, Montreal Cognitive Assessment (MoCa) < 20
• Other neurological or medical condition that caused sustained clinically relevant gait and/or postural stability deficits
• 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 assessments
• 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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Switzerland · 1 center

• University of Zurich — Zurich

Identifiers

NCT: NCT07082595 · StimuLOOP_PD-S · 2024-01941

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗