Clinical trial NCT02443857: Feasibility of a New Pediatric Arm Rehabilitation Robot ChARMin
Official title: Feasibility of a New Pediatric Arm Rehabilitation Robot ChARMin: A Monocentric Interventional Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Nervous System Diseases
Lead sponsor: University Children's Hospital, Zurich
Sponsor class: OTHER
First posted: 2015-05-14
Enrollment: 430
Sex: ALL
Minimum age (years): 5
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this study is to investigate the applicability and feasibility of the newly developed robot platform for upper extremity therapy ("ChARMin") in children undergoing neurorehabilitation.

Detailed description: Background and Rationale: Children with neurological diagnoses including congenital or acquired brain lesions often have impaired upper extremity function that limits activities of daily life and independence. While several rehabilitation technologies in the clinical routines are being applied to improve upper extremity functions in these patients, the technology to train more severely affected children was not available so far. Since 3 years, the investigators are working together with the Sensory-Motor Systems Lab at ETH Zurich on a new robot platform specifically developed for upper extremity therapy in children (the 'Children's Arm Rehabilitation Mechatronic Interface' or 'ChARMin'). This group showed recently in a single blinded RCT that their adult upper extremity robot ARMin is an effective neurorehabilitation tool for adults after stroke (especially for the more severely affected patients). Now, that ChARMin is finished the investigators would like to study whether it is feasible to apply this prototype to children and adolescents undergoing neurorehabilitation.

Objective(s): As ChARMin was specifically developed for children and adolescents, the investigators first want to explore whether it is feasible to apply it to children and adolescents undergoing neurorehabilitation. Six studies will be performed with the following main objectives: (i) to investigate the applicability (technical aspects, patient-related aspects, operability/handling of the robot, the different control modes of the device, safety and the software interface) of ChARMin; (ii) to determine whether differences between game scores, kinematic and kinetic metrics provided by ChARMin, additionally applied physiological measures and adverse events differ when participants train with the free non-supported mode, the assist-as-needed mode and the fully guided mode; (iii) to determine the psychometric properties (validity, reliability and responsiveness) of the assessments integrated in ChARMin; (iv) to describe the application of the system in 30 participants and evaluate the concomitant changes in upper extremity motor function (open labelled interventional study without control group); (v) specific motor learning studies in 120 patients investigating whether children with neurological diagnoses can improve arm and hand task performance during repetitive training with ChARMin, are able to retain improved levels of task performance and how task performance is influenced by other interventions; (vi) to perform an ecological study monitoring safety, functional progress and (changes in) the application of ChARMin in 120 participants following an in- or out-patient program (comparable to subproject iv).

Outcome(s): The outcomes are in line with the objectives of each subproject. Some outcome measures are specifically performed for this study (e.g. safety, game scores, assessments integrated in ChARMin), others are clinically routinely applied measures (no additional burden for the patient). The investigators do not apply any invasive tools and assure that the amount of additional assessments will be limited to keep the burden for the participants acceptable.

Study design: Most projects are open labelled interventional studies investigating the applicability, safety and usability of a newly developed upper extremity robot ChARMin. Project (i) will investigate the feasibility of ChARMin in 30 children and adolescents. Project (ii) will be a randomized study investigating differences in the various measures between the 3 control modes of ChARMin. Project (iii) include psychometric studies where a single measurement is necessary (validity), or two repeated measurements are performed (within 3-7 days to determine reliability and between onset and end of rehabilitation to determine responsiveness). Project (v) consists of motor learning studies where a large number of repetitions are performed in a relative short time to determine changes in task performance, retention and generalizability. Projects (iv) and (vi) are open labelled interventional studies investigating the application of ChARMin and concomitant changes in upper extremity function without control group.

Measurements and procedures: Participants will be positioned in a comfortable position on a chair. After the required anthropometrics have been assessed, the ChARMin is adjusted and the cuffs of ChARMin will be fixated to the patient. Depending on the study, the participant will be informed and instructed what task/assessment or game will be made and what the goal is. Then, the participant will perform the task, while the investigator/therapist will be there to answer any questions, make sure the patient is comfortable, and to control the device, including the emergency buttons. Afterwards, the investigator/therapist will loosen the cuffs and assist if needed the participant getting out of the chair. The therapist will control the participant's skin and will ask for any other signs of discomfort. The duration of a session will remain within 45 minutes. In other sessions, clinical routine assessments will be performed.

Study Product / Intervention: The Children's Arm Rehabilitation Mechatronic Interface (ChARMin) is a newly developed upper extremity exoskeleton robot which can assist single joint movements and complex spatial reaching movements involving movements for shoulder, elbow, wrist and hand. As several subprojects are performed, the intervention could last a single training session of about 45 minutes, two or three sessions (for example to investigate reliability of assessments) or a longer training duration as prescribed by the medical doctor (e.g. for several weeks 3-5 times per week, as part of an intense a rehabilitation program).

Control Intervention (if applicable): NA (subproject 2: each child is its own control)

Number of Participants with Rationale: In general, the investigators plan to include about 30 participants per project as this number would results in a more or less normal distribution, and for psychometric studies, this is the number of participants needed to score a psychometric study of sufficient quality to be included in a best evidence synthesis.

Subproject (i): 30 participants. Subproject (ii): 30 participants. For subproject (iii) the investigators plan to recruit 60 participants (with at least 2 measurements per participant). Likely, the number might be smaller if participants agree to undergo 3 assessment sessions (first for validity, second for reliability and a final one for responsiveness). Reference values will be obtained in 40 healthy participants.

Subproject (iv): 30 participants. Subproject (v): Pilot motor learning studies will be performed in 40 participants, while the definite motor learning studies will be performed in 80 participants.

Subproject (vi): 120 participants. Please note, participants will likely contribute to more than 1 subproject with no high burden. Therefore, the total number of patients will therefore likely be smaller than 390.

Study Duration: 5 years

Study Schedule: Month Year of First-Participant-In (Mai 2015). Month Year of Last-Participant-Out (April 2020)

Study Centre(s): Monocentric study: Rehabilitation Center Affoltern am Albis

Statistical Considerations: The investigators will mainly report descriptive statistics. Normal distribution will be determined with the Shapiro-Wilk test. Comparisons between two dependent groups will be performed with Wilcoxon's or paired-t-test. Comparisons between two independent groups will be performed with a Mann-Whitney U test or a Student's t-test. Differences between three groups will be determined with a Friedman's test (dependent groups) or an ANOVA (independent groups). Relationships will be analysed with a Spearman's or Pearson correlation coefficient. Motor learning will be quantified with various measures: learning or adaptive rate will be fitted with a power or exponential regression; ratios will be calculated to quantify the transfer or retention between blocks of trials and retention.

GCP Statement: This study will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the ICH-GCP or ISO EN 14155 (as far as applicable) as well as all national legal and regulatory requirements.

Eligibility criteria: Inclusion Criteria:

* Age between 5 and 21 years
* Neurological diagnoses
* Impairment of the upper extremity (for projects (i) and (ii) we might also include patients without upper extremity impairments to cover a wide range of patients with different abilities)
* Other (non-neurological) diagnoses, who require intense training of the upper extremity

Exclusion Criteria:

* Strong adipositas, which makes it not possible to adjust the cuffs and orthoses to the anthropometrics of the participant
* Fixed contractures of the upper extremity that should be positioned in ChARMin
* Instabilities of bones or joints, fractures or osteoporosis/osteopenia
* Allergy against material of cuffs
* Open skin lesions of the upper extremity that should be positioned in ChARMin
* Luxations or subluxations of joints of the upper extremity that should be positioned in ChARMin
* Strong pain that increases while training in ChARMin\*
* Injuries or lesioned nerves of the upper extremity that should be positioned in ChARMin\*
* Strong spontaneous movements like ataxia, dyskinesia, myoclonus\*
* Instable vital functions like pulmonal or cardiovascular conditions
* Implanted pace maker, defibrillator of the heart
* Implanted shunt by hydrocephalus\*
* Implanted cochlear or baha\*
* Uncooperative or aggressive behaviour
* Known or suspected non-compliance
* Severe cognitive deficits
* Inability to signal pain or discomfort
* Apraxia\*
* Severe visual impairment (inability to see the screen)
* Severe spasticity (Ashworth 4)
* Severe epilepsy\*
* Insufficient head stability
* Infections requiring isolation of the patient Contraindications marked with an \* are relative contraindications. Final approval needs to be obtained from the medical doctor.

Primary outcomes:
measure: ChARMin-1: Score on the feasibility questionnaire [points]
timeFrame: Up to 8 weeks
measure: ChARMin-2: Game Scores [points]
timeFrame: up to 24 weeks
measure: ChARMin-3: Assessment battery integrated into the ChARMin software [points]
timeFrame: Up to 24 weeks
measure: ChARMin-3: Change from baseline of the assessment battery integrated into the ChARMin software [delta points]
timeFrame: Twice within 3-7 days
measure: ChARMin-3: Change from baseline of the assessment battery integrated into the ChARMin software
timeFrame: At onset and end of the hospital stay, which covers an expected average of 7 weeks
measure: ChARMin-4 and ChARMin-6: Change from baseline in the Box and Block Test [delta of the number of blocks transferred]
timeFrame: At onset and end of hospital stay, which covers an expected average of 7 weeks
measure: ChARMin-5: Game scores [points]
timeFrame: up to 24 weeks
Secondary outcomes:
measure: ChARMin-2: Joint angle measures provided by ChARMin [degrees]
timeFrame: up to 24 weeks
measure: ChARMin-2: Force measures provided by ChARMin [Newton]
timeFrame: up to 24 weeks
measure: ChARMin-2: Amplitude of muscle activation [microVolt]
timeFrame: up to 24 weeks
measure: ChARMin-2: Palmar skin conductance [microVolt]
timeFrame: up to 24 weeks
measure: ChARMin-2: Heart rate [beats per minute]
timeFrame: up to 24 weeks
measure: ChARMin-2: Adverse events [number and kind of events]
timeFrame: up to 24 weeks
measure: ChARMin-2: Score on the motivational questionnaire [points]
timeFrame: up to 24 weeks
measure: ChARMin-4 and ChARMin-6: Change from baseline in the score of the assessment battery integrated into the ChARMin software [delta points]
timeFrame: At onset and end of hospital stay, which covers an expected average of 7 weeks
measure: ChARMin-4 and ChARMin-6: Change from baseline in the Nine-hole Peg Test [delta seconds]
timeFrame: At onset and end of hospital stay, which covers an expected average of 7 weeks
measure: ChARMin-4 and ChARMin-6: Change from baseline in the brain reorganization measured by transcranial magnetic stimulation [delta milliseconds]
timeFrame: At onset and end of hospital stay, which covers an expected average of 7 weeks
measure: ChARMin-4 and ChARMin-6: Change from baseline in strength of fingers and hand [delta Newton]
timeFrame: At onset and end of hospital stay, which covers an expected average of 7 weeks
Other outcomes:
Locations:
city: Affoltern am Albis
country: Switzerland
facility: Rehabilitation Center for Children and Adolescents of the University Children's Hospital Zurich
Study officials:
affiliation: Rehabilitation Center for Children and Adolescents of the University Children's Hospital Zurich
name: Hubertus JA van Hedel, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Graser JV, Prospero L, Liesch M, Keller U, van Hedel HJA. Test-retest reliability of upper limb robotic exoskeleton assessments in children and youths with brain lesions. Sci Rep. 2022 Oct 6;12(1):16685. doi: 10.1038/s41598-022-20588-8.
citation: Graser JV, Bastiaenen CHG, Gut A, Keller U, van Hedel HJA. Contextual interference in children with brain lesions: a pilot study investigating blocked vs. random practice order of an upper limb robotic exergame. Pilot Feasibility Stud. 2021 Jun 25;7(1):135. doi: 10.1186/s40814-021-00866-4.
citation: Graser JV, Bastiaenen CHG, Keller U, van Hedel HJA. Contextual interference in children with brain lesions: protocol of a pilot study investigating blocked vs. random practice order of an upper limb robotic exergame. Pilot Feasibility Stud. 2020 Oct 15;6:156. doi: 10.1186/s40814-020-00694-y. eCollection 2020.