Effects of Tele-prehabilitation in Patients Waiting for Knee Replacement

Study Overview
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Brief Summary
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After knee arthroplasty rehabilitation is fundamental to patient's functional recovery, but in recent years there has been a growing interest in the possibility to prepare patients for surgery through a prehabilitation program. This two-parallel groups randomized clinical trial aims at evaluating the effects of a preoperative rehabilitation programme carried out at patient's home using advanced technologies, on subjects waiting for knee replacement. In particular, the primary objective of this study is to assess the superiority of a tele-prehabilitation programme compared to standard prehabilitation (remotely delivered with a booklet) in determining an improvement in lower limb function, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire, at the end of the programme. This study also aims at assessing possible differences between groups in muscle function, pain, autonomy in the activity of daily living, adherence to treatment and patients' satisfaction with the prehabilitation modality. Through the analysis of quadriceps muscle and blood samples, we will also evaluate possible changes in the expression of specific markers that the prehabilitation programme may be able to determine at muscle level. Both the intervention and the control groups will perform a prehabilitation program in the 6 weeks just before surgery. The program will include therapeutic exercises and educational contents. Subjects in the tele-prehabilitation group will receive a tablet with two accelerometers and a balance board for the remote execution of the program, while the control group will receive the same intervention through a booklet. Subjects recruited will be assessed at 5 timepoints: before starting the prehabilitation program, the day of surgery, 7± 2 and 15 ± 2 days after surgery, 3 months ± 7 days after surgery.

Detailed Description
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Based on the existing literature, we expected to observe an effect size of 0.8 in WOMAC (primary outcome) between groups at the end of the tele-prehabilitation program. Therefore, considering a test power of 80% and an alpha error of 5%, we have computed a sample size of 48 subjects, 24 for each group (taking into account a possible drop-out rate of 15-20%). Ten healthy young subjects will be also recruited only for muscle and blood samples collection, that will be used as benchmarks for the intervention and control groups analyses (they will no undergo any prehabilitation program). The recruited subjects will be randomly allocated (with a 1:1 ratio randomization list) in the tele-prehabilitation or in the control groups. During the 6 weeks just before surgery, both groups will perform 5 sessions a week of the same home-based prehabilitation program. Each session is planned as follow: 5 minutes of warm-up, 30 minutes of work (mobility, strengthening and balance exercises) and 5 minutes of cool-down. In details, for each session subjects will perform the following exercises: Warm-up (about 5 minutes) Knee bending and extension in lying position; Knee extensions while sitting; Get on tiptoes in standing position; March on site. Working phase (about 30 minutes) Hip bending keeping the knee extended in lying position; Hip motion in space planes (imagining of drawing numbers with the tiptoe); Hip abduction keeping the knee extended side lying; Knee bending and hip extension in standing position; Half squat; Half lateral lunge; Monopodalic standing; Tandem walking; Weight shifting on unstable surface. Cool-down (about 5 minutes) Free walk; Leg swings while sitting. Subjects of both groups will also have to read, once a week, an educational content (digital for the tele-prehabilitation group, printed for the control one) dealing with: Information about knee osteoarthritis and replacement; Post-operative symptoms, what to expect; Advices for home organization after surgery; Healthy life style: physical activity, nutrition and sleep; Advices for maintaining progresses; Motivational intervention. The tele-prehabilitation program will be delivered using the following devices (Khymeia, Padova, Italy -Khymeia - e-health innovation): TeleCockpit, a workstation used by the clinician to manage remotely patient's home device, interact real-time or check the adherence to treatment; VRRS Home Tablet, with an uploaded mobile application for the exercises execution at home; VRRS Khymu, two accelerometers for patient's interaction with the virtual reality system during knee motion; VRRS Balance, a balance board for patient's interaction with the virtual reality system during centre-of-mass motion. The exercise volume of the work section of the prehabilitative session will increase during the 6 weeks according to patient's symptoms. This progression will be based on the score, measured at the end of each workout, obtained at the Borg CR-10 scale self-administered by the patient at the end of each session. A score below 5 indicates the need to increase the workload in the next session. The progression of the working volume will be considered and eventually managed weekly by the clinician in charge, for the intervention group connecting to the patient's device with the TeleCockpit workstation, and for the control group by communicating the changes in the prescription details with a phone call.

Official Title
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Effects of Tele-prehabilitation on Clinical and Muscular Recover in Patients Waiting for Knee Replacement: a Randomized Controlled Trial

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Other: Tele-prehabilitation
* Other: Standard prehabilitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for TELE-pre and Con-O groups (also previous information are valid only for these groups): Scheduled unilateral total knee replacement surgery according to Fast-Track pathway; Preoperative criteria for home discharge; At least one person cohabitant; Familiarity with tablet/computer use and Internet access; Informed consent signature. Inclusion Criteria for Con-Y group: Male sex of any ethnicity; Age between 18 and 30 years; Scheduled Anterior Cruciate Ligament reconstruction surgery; Body Mass Index ≤ 30. Exclusion Criteria for TELE-pre and Con-O groups: Scheduled surgery for knee revision arthroplasty; Lower limbs surgery in the previous 6 months; Lower limbs fractures in the previous 6 months; Congenital or post-traumatic knee morphologic alterations; Rehabilitation treatments in the previous 6 months focused on the interested knee functional recovery; Ongoing neurological or oncological diseases; HIV, HCV, HBV, TPHA infection; Cognitive impairment; Known local anaesthetics allergic reactions; Ongoing non-suspendable anticoagulant therapies; Known muscular diseases. Exclusion Criteria for Con-Y group: Body Mass Index > 30; Ongoing oncological diseases; Sampling area infection; HIV, HCV, HBV, TPHA infection; Known neuromuscular/muscular diseases; Ongoing non-suspendable anticoagulant therapies.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TELE-pre group<br>Subjects in the TELE-prehabilitation group receive remote prehabilitation using advanced technologies. | Other: Tele-prehabilitation<br>* Preoperative tele-rehabilitation using a virtual reality system.<br>|
| Active Comparator: Control group<br>The control group is composed by the Con-O (Control Older) group and the Con-Y (Control Young) group. In the Con-O group (n=24) subjects receive home-based prehabilitation using a printed booklet; in the Con-Y group (n=10) subjects do not receive any prehabilitation program. Subjects in the Con-Y group will be recruited from patients waiting for anterior cruciate ligament reconstruction, thus they will be only assessed with muscular biopsy and blood sampling. | Other: Standard prehabilitation<br>* Preoperative home-based rehabilitation delivered with a printed booklet for the Con-O subjects and no intervention for the Con-Y subjects.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 6/7 weeks | The WOMAC questionnaire is a self-administrated health status measure for pain, stiffness and function assessment in patients with hip or knee osteoarthritis. It is composed by 24 items and uses a 5-point Likert scale (from 0 to 4). | The day of the recruitment (T0); 6/7 weeks after T0, the day of surgery (T1). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) | The WOMAC questionnaire is a self-administrated health status measure for pain, stiffness and function assessment in patients with hip or knee osteoarthritis. It is composed by 24 items and uses a 5-point Likert scale (from 0 to 4). | 7 +/- 2 days after surgery (T2); 15 +/- 2 days after surgery (T3); 90 +/- 7 days after surgery (T4) | 
| Oxford Knee Score (OKS) | The OKS is a self-administrated questionnaire assessing symptoms and function in patients undergoing knee replacement. It is composed by 12 items and uses a 5-point Likert scale. | The day of the recruitment (T0); 6/7 weeks after T0, the day of surgery (T1); 7 +/- 2 days after surgery (T2); 15 +/- 2 days after surgery (T3); 90 +/- 7 days after surgery (T4) | 
| Numeric Pain Rating Scale (NPRS) | The NPRS is an 11-point scale from 0 to 10 assessing pain. 0 is no pain, 10 is the most intense pain imaginable. | The day of the recruitment (T0); 6/7 weeks after T0, the day of surgery (T1); 7 +/- 2 days after surgery (T2); 15 +/- 2 days after surgery (T3); 90 +/- 7 days after surgery (T4) | 
| Short Form-12 | The Short Form-12 is questionnaire for health assessment, composed by 12 items, which can be self-administrated or completed through an interview. An algorithm is used to obtain the final composite score. | The day of the recruitment (T0); 6/7 weeks after T0, the day of surgery (T1); 7 +/- 2 days after surgery (T2); 15 +/- 2 days after surgery (T3); 90 +/- 7 days after surgery (T4) | 
| International Physical Activity Questionnaire (IPAQ) | The IPAQ is a 9-item self-reported measure of physical activity. Adding up the week minutes of walking, moderate-intensity activity and vigorous-intense activity, multiplied per specific coefficients, the questionnaire estimate the overall Metabolic Equivalent of Task. | The day of the recruitment (T0); 6/7 weeks after T0, the day of surgery (T1); 7 +/- 2 days after surgery (T2); 15 +/- 2 days after surgery (T3); 90 +/- 7 days after surgery (T4) | 
| Sit-to-stand test | The subject is asked to stand-up and sit-down on a chair, standardized in size, for 5 consecutive times as much faster as he can. Time (in seconds) to complete the task is representative of the lower limb strength. | The day of the recruitment (T0); 6/7 weeks after T0, the day of surgery (T1); 7 +/- 2 days after surgery (T2); 15 +/- 2 days after surgery (T3); 90 +/- 7 days after surgery (T4) | 
| Knee extensor and flexors maximal strength assessment | Maximal strength will be assessed using a dynamometer and expressed in kilograms (Kg). | The day of the recruitment (T0); 6/7 weeks after T0, the day of surgery (T1); 7 +/- 2 days after surgery (T2); 15 +/- 2 days after surgery (T3); 90 +/- 7 days after surgery (T4) | 
| Timed Up-and-Go test | The subject is asked, starting from seated on a chair, to stand-up, walk 3m, go back to the chair and sit-down. Time (in seconds) to complete the task is representative of the subject's risk of fall. | The day of the recruitment (T0); 6/7 weeks after T0, the day of surgery (T1); 7 +/- 2 days after surgery (T2); 15 +/- 2 days after surgery (T3); 90 +/- 7 days after surgery (T4) | 
| Knee Range Of Motion | Knee motion in flexion and extension is measured using a goniometer and expressed in degree. | The day of the recruitment (T0); 6/7 weeks after T0, the day of surgery (T1); 7 +/- 2 days after surgery (T2); 15 +/- 2 days after surgery (T3); 90 +/- 7 days after surgery (T4) | 
| Satisfaction interview | This interview is a 6-item self-reported measure of participant's satisfaction about the prehabilitation delivery modality, which uses a 11-point Likert scale. This interview has been created ad hoc for this study. | 6/7 weeks after T0. | 
| Prehabilitation diary | This diary has been created ad hoc to assess participant's adherence to treatment. The measure of adherence is expressed by the total number of sessions reported in the diary. It will be used only to assess adherence of the Con-O group. | 6/7 weeks after T0. | 
| Muscle metabolism markers | Muscle will be sampled by needle aspiration (for participants belonging to Tele-pre or Con-O groups) or discarded muscle material collection during surgical procedures. In collected muscle samples, myosin heavy chain (MHC) isoform distribution will be assessed by SDS-PAGE electrophoresis, while levels of markers as PGC1alpha will be investigated by ELISA or Western Blot. Proteomics analysis will be conducted by LC-MS, using TMT quantification, whereas lipidomics and sphingolipidomics analyses will be conducted by untargeted and targeted LC-MS. | The day of the recruitment (T0); the day of surgery (T1); 90 +/- 7 days after surgery (T4) | 
| Blood biomarkers | Blood sample will taken according to standard procedures. Levels of proteins or lipids suggested to be potential biomarkers will be investigated in collected sera, by ELISA or MRM-MS. | The day of the recruitment (T0); the day of surgery (T1); 90 +/- 7 days after surgery (T4) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tele-prehabilitation, Prehabilitation, Virtual Reality, Advanced technologies, Knee osteoarthritis, Arthroplasty, Replacement, Knee