Clinical trial NCT05229185: Error-enhancement for Arm Rehabilitation Post Stroke
Official title: Error-enhancement as Basis for Novel Upper Limb Rehabilitation in the Chronic Phase After Stroke: a 5-day Pre-post Intervention Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Chronic Stroke
Keywords: upper limb
neurorehabilitation
error-enhancement
robotic treatment
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: KU Leuven
name: Bioxtreme Ltd.
First posted: 2022-02-08
Enrollment: 22
Sex: ALL
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study has a pre-post intervention design, recruiting 20 patients in the chronic phase after stroke. Pre- and post-intervention assessments are administered on day 1 and 7.The 5 days in between, all patients receive the same training with the robot, there is no control group.
Primary purpose: TREATMENT

Brief summary: Even in a chronic phase after stroke, most patients have difficulty moving the affected arm, resulting in limitations in simple tasks in daily living, most frequently limiting reaching task. In the chronic phase, significant improvements are usually no longer observed. Nevertheless, even these patients can still improve their functional abilities due to exercise-dependent plasticity.

A new device was developed, the deXtreme robot, a rehabilitation device that offers error-enhancement approach during three-dimensional movements. The goal error-enhancement is to elicit better accuracy, stability, fluidity and range of motion during reaching. games are projected on a screen, requiring 3D active reaching movements. The duration of the study for a single participant will be 7 consecutive working days, including 1 day of pre-intervention assessment, 5 days of training and 1 day of post-intervention assessment. The overall aim of this project is to gain knowledge into the potential of error-enhancement robot training in patients with upper limb impairments in the chronic phase after stroke. Hypothesizing that the 5-day training will have a positive effect on both the robotic and clinical outcome measures.

Detailed description: The overall aim of this study is to gain knowledge into the potential of error-enhancement robot training in patients with upper limb impairments in the chronic phase after stroke. Error-enhancement is characterized as unexpected external perturbation forces acting upon the upper limb during a reaching movement, causing the upper limb to deflect from the reaching pathway, and this results in errors. If one allows for repetitive reaching performance with the same systematic perturbation forces, then a decrease in errors and improvement in movement performance is expected. The robot used for the training, the DeXtreme, is a CE marked rehabilitation device that offers this error-enhancement approach during three-dimensional movements.

The pilot study has a pre-post intervention design, recruiting 20 patients in the chronic phase after stroke. Error-enhancement treatment will be provided on day 2 to 6, i.e., for 5 consecutive days and will consist of facilitation of accuracy, range of movement, stability, and smoothness. Algorithms provide progression in terms of accuracy, range of movement, stability and smoothness, depending upon the performance of the patient.

The treatment will start with the installation of the patient and a warming up, followed by a first block of DeXtreme training. Then a short break is given followed by a short conventional therapy session. The content of the conventional therapy will involve active relaxation, focusing on stretching and (auto-)mobilisation. Afterwards, a second block of training with the DeXtreme follows, and it finishes with a cooling down. A therapist trained by the company will provide all assessment and training sessions. Training with the DeXtreme is additional to the conventional therapy the patient receives. Therefore, a diary of their conventional therapy sessions will be kept, and the content will be reviewed with the patient.

Advancements in upper limb motor function and activity will be evaluated through a triad of measurements including clinical and patient-reported outcomes, error-enhancement variables, and objective quantification of uni- and bimanual sensorimotor function by making use of the KINARM robotic manipulandum. These tests and questionnaires are administered on day 1 and day 7.

The aim of the study is to investigate whether patients with upper limb impairments in a chronic phase after stroke clinical and meaningful benefits from 5 hours DeXtreme training. In addition, it is examined whether improvements in the upper limb outcome is the result of restitution or compensation in the upper limb function.

In order to evaluate whether a randomized controlled trial is useful, the investigators will analyse the outcomes of our study twofold. (1) At group level, the investigators will calculate mean and standard deviation or median and interquartile range (based on whether data is normally distributed or not) and evaluate whether pre- to post-intervention scores for clinical, deXtreme and objective outcomes are significantly improved by means of Wilcoxon signed rank test (nonparametric), at a 0,05 significance level. Each p-value will be interpreted in a descriptive manner.

(2) At patient level, the investigators will evaluate how many patients (%) achieve a clinically significant improvement based on the therapy provided.

To see if the improvement might be explained by restitution or compensation, the association between the scores of the MAL-14 and the visually guided reaching task of the KINARM will be explored by Spearman correlations.

Eligibility criteria: Inclusion Criteria:

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
2. First stroke, confirmed by neurologist based on clinical and/or imaging findings
3. Ischemic/hemorrhagic stroke, at least more than six months ago
4. Stroke affecting the dominant/non-dominant upper limb (unilateral weakness)
5. Less than 85 years old
6. Having a motor impairment yet no severe spasticity in the upper limb: be able to open and close the hand 5 times and be able to flex and extend the elbow 2 times but score less than 66 (maximum) on the Fugl-Meyer Assessment.

Exclusion Criteria:

1. Having sensory aphasia (evaluated by item 9 of the National Institutes of Health Stroke Scale)
2. Having apraxia (evaluated by the apraxia screen of TULIA)
3. Having neglect (evaluated by the Star Cancellation Test)
4. Cognitive deficit with a score under 24 out of 30 on the Mini-mental State Examination
5. Shoulder pain (yes/no)
6. Providing no informed consent

Primary outcomes:
measure: Action research arm test
timeFrame: day 1(pre) - day 7 (post)
measure: Fugl-Meyer motor assessment upper extremity
timeFrame: day 1(pre) - day 7 (post)
measure: Kinarm: visually guided reaching task
timeFrame: day 1(pre) - day 7 (post)
measure: DeXtreme: reaching task - Market stand
timeFrame: day 1(pre) - day 7 (post)
measure: DeXtreme: reaching task - Alchemist
timeFrame: day 1(pre) - day 7 (post)
Secondary outcomes:
measure: Visual analogue scale (VAS) - Pain
timeFrame: day 1(pre) - day 7 (post); after treatment (day 2-5)
measure: Motor assessment scale - tonus
timeFrame: day 1(pre) - day 7 (post); after treatment (day 2-5)
measure: Kinarm: sensory processing task
timeFrame: day 1(pre) - day 7 (post)
measure: Motor assessment scale - upper limb
timeFrame: day 1(pre) - day 7 (post)
measure: Stroke impact scale - Hand
timeFrame: day 1(pre) - day 7 (post)
measure: Motor Activity Log - 14 items
timeFrame: day 1(pre) - day 7 (post)
measure: Kinarm: arm position matching task
timeFrame: day 1(pre) - day 7 (post)
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams-Brabant
Study officials:
affiliation: KU Leuven
name: Geert Verheyden
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kim RK, Kang N. Bimanual Coordination Functions between Paretic and Nonparetic Arms: A Systematic Review and Meta-analysis. J Stroke Cerebrovasc Dis. 2020 Feb;29(2):104544. doi: 10.1016/j.jstrokecerebrovasdis.2019.104544. Epub 2019 Dec 6.
citation: Ward NS, Brander F, Kelly K. Intensive upper limb neurorehabilitation in chronic stroke: outcomes from the Queen Square programme. J Neurol Neurosurg Psychiatry. 2019 May;90(5):498-506. doi: 10.1136/jnnp-2018-319954. Epub 2019 Feb 15.
citation: Israely S, Leisman G, Carmeli E. Improvement in Hand Trajectory of Reaching Movements by Error-Augmentation. Adv Exp Med Biol. 2018;1070:71-84. doi: 10.1007/5584_2018_151.
citation: Huang VS, Haith A, Mazzoni P, Krakauer JW. Rethinking motor learning and savings in adaptation paradigms: model-free memory for successful actions combines with internal models. Neuron. 2011 May 26;70(4):787-801. doi: 10.1016/j.neuron.2011.04.012.