Clinical trial NCT03237520: Comparing Virtual Reality Therapy With Modified-CIMT Versus Modified-CIMT Alone in Hemiparetic Children
Official title: Comparing Efficacy of Virtual Reality Therapy With Modified Constraint Induced Movement Therapy (mCIMT) Versus mCIMT Alone, for 5-18 Years Children With Hemiparetic Cerebral Palsy - An Open Label, Randomized Controlled, Superiority Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hemiparesis
Lead sponsor: All India Institute of Medical Sciences
Sponsor class: OTHER
First posted: 2017-08-02
Enrollment: 60
Sex: ALL
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: An open labeled, randomized controlled, parallel design, superiority trial
Primary purpose: TREATMENT

Brief summary: This study intends to compare the efficacy of of virtual reality therapy(VRT) with modified constraint induced movement therapy(mCIMT) versus modified constraint induced movement therapy alone for children with hemiparetic cerebral palsy aged \>/= 5-18 years, in improving the upper limb functions, as measured by the QUEST (Quality of Upper Extremity Skill Test score) over 3 months of intervention.

Detailed description: Sample size: Based on the previous studies, on CIMT in hemiparetic CP children using QUEST scores,

* Anticipated increase in total QUEST scores at 2 months in the mCIMT group:

  10 + 5(mean + SD)
* Anticipated increase in total QUEST scores at 2 months in the mCIMT+ VRT group:

  15 + 5(mean + SD)
* Alpha error= 5%
* Power= 80%
* Calculated sample size : 23 children in each group
* Considering loss due to attrition of roughly 25%,investigators would enroll 30 children in each of the two groups.
* At least 10 children in each group will be analyzed with baseline and follow up fMRI and DTI. These children in each group will be selected through systematic sampling method.

Method:

* Block randomization in 1:1 ratio with variable block size will be done using computer generated random numbers. These will be generated by the person not involved in the trial. Subjects will be randomized to

  * mCIMT + VRT
  * mCIMT alone
* Each random number will be kept in an opaque sealed envelope and will be opened only at the time of enrollment of the study subjects.Principal investigator will then enroll the participants, and will assign the participants to interventions. After obtaining informed consent from parents, and assent from the children participating in the trial(whenever possible), of hemiparetic cerebral palsy, subjects will be enrolled in the study as per the inclusion and exclusion criteria. Details for each patient will be recorded in a structured proforma

The total study duration will be 3 months, of which 2 months of supervised intervention will be given.Home based therapy will be continued all through the 3 months of intervention in both the groups.

* Functional assessment of the upper limbs will be done using QUEST/Nine Hole Peg Board Test/ Hand Held Dynamometer and quality of life by cerebral palsy quality of life(CP-QOL)- child scale. Baseline fMRI(Functional Magnetic Resonance Imaging) and DTI(Diffusion Tensor Imaging) Brain will be performed up to one week before starting intervention.
* Baseline fMRI and DTI will be done in at least 10 children of each group, selected by systematic sampling method within each group.
* mCIMT+ VRT program will be initiated within one week of baseline assessment, at the institute(Department of PMR). There will be 12 visits over the duration of intervention for supervised sessions, in each group. It would be twice weekly for 4 weeks followed by once a week for next 4 weeks. Parents will be advised regarding the therapy to be provided at home on these visits. Compliance log will be provided to them at the first visit
* Compliance log will be checked on each subsequent visit; reinforcement will be provided; video records of one session per week of each item of mCIMT done at home will also be reviewed. Those following regimen for \<70 % of the total time recommended for mCIMT each day for at least 21 out of 28 days will be considered to be poorly compliant. Those following regimen for \>80% of the total time recommended for mCIMT each day for at least 21 out of 28 days will be considered to have compliance. Those following the regimen for 80-90% of the total time recommended for mCIMT each day for at least 21 out of 28 days will be considered to have fair compliance.Those following the regimen for \>90% of the total time recommended for mCIMT each day for at least 21 out of 28 days will be considered to have good compliance.\[All children(both with good and poor compliance), will be included in the intention to treat analysis\]

CIMT(Control group and intervention group) :

• Sling will be applied to the unaffected arm, as a restraint (sling will be provided free of cost). mCIMT will be performed for 2 hours per session during the scheduled visits(in the control group) and 2 hours every day at home(by both the groups). Functional activities will be carried out by the affected, unrestrained arm under supervision. Repetitive activities and shaping will be practiced. mCIMT will be provided by trained occupational therapist, first investigator and with the caregiver's participation and would be tailor made to each patient. At each visit, the methodology followed at home will be reviewed (log books with/without video records). Reinforcement will be provided at each visit regarding subsequent therapy to be done at home.

VRT(Intervention group only):

* VRT software and device is developed in collaboration with IIT Delhi using Kinect system. Kinect- motion sensor and computer set up is required. VRT (CIMT in a virtual environment)will be provided for 2 hours at every visit(twice weekly for first 4 weeks, once a week for next 4 weeks). VRT will be provided only during scheduled visits with the same principle as mCIMT. Functional activities like repetition of the tasks and shaping will be performed with the affected hand using VRT and CIMT while the unaffected arm is restrained. At home, 2 hours of modified CIMT will be given daily, as for the control group. At each visit, the methodology of CIMT followed at home is reviewed (log books with/without video records). Reinforcement will be provided at each visit regarding subsequent therapy to be done at home
* FMRI and DTI will be done within 1 week of completion of 08 weeks of intervention in all those children who have had a baseline fMRI/DTI.
* After 8 weeks of intervention, children will be followed up again at the end of 12 weeks from the baseline. They will be asked to continue mCIMT daily for 2 hours at home and maintain the daily logs during this period. At this visit, all clinical assessments will be repeated
* Outcome assessors will be blinded to the study subject's group allocation.
* Data will be recorded in a pre-designed proforma and managed in an excel spread sheet.All the entries will be checked for any possible key board errors. Statistical analysis will be done using Stata 14.0 statistical software.
* Intention to treat analysis and per protocol analysis will be done
* Categorical variables will be summarized by frequency (%) and test of proportions will be used to compare the proportions between the two groups. Quantitative variables will be assessed for approximate normal distribution and these will be denoted as mean+SD or median (Interquartile range/min-max), as appropriate.Student's t test/ Wilcoxon rank sum test will be used to compare the mean value between the two groups at the end of the intervention and at the end of 3 months. In case of any imbalance at the baseline, analysis of covariance(ANCOVA) will be used to compute adjusted mean of the outcome variables bet the two groups and the corresponding effect size(95%CI).In this study p value \<0.05 will be considered statistically significant.

Eligibility criteria: Inclusion Criteria:

1. Children aged \>5-18 years
2. Children with hemiparetic cerebral palsy \* (both perinatal and postnatal acquired brain injury)
3. Intelligence quotient \>70 (Binet Kamat Test/Malin's Intelligence Scale for Children)
4. Modified Ashworth scoring 1-3 for affected limb
5. Can sit independently or with support (Gross Motor Functional Classification System stage: 1-4 and Manual Ability Classification System stage: 1-3)
6. Preserved vision and hearing (with or without correction)

Exclusion Criteria:

1. Uncontrolled epilepsy as defined by seizure frequency \>1/month for preceding 3 months
2. Severe concurrent illness or diseases not associated with CP or unstable medical conditions like pneumonia
3. Genetic or syndromic associations
4. Children diagnosed with autistic spectrum disorders
5. Modified Ashworth scale score more than 3 at shoulder/elbow /wrist
6. Contractures of the affected limb
7. Severe movement disorder like dystonia, choreo-athetosis or ballismus interfering with purposeful limb movement
8. Any congenital brain malformation detected on conventional MRI brain
9. Recent orthopedic surgery/cast/splint in the affected limb
10. Botulinum toxin/phenol blocking in the affected limb in the past 6 months or are planning to receive in the study period
11. Those receiving tone modifying agents in week before enrollment(Tizanidine,baclofen,benzodiazepines,dantrolene)
12. Any contraindications for MRI - examples- presence of pacemaker, metallic implant

Primary outcomes:
measure: 8 weeks of VRT with mCIMT versus mCIMT alone
timeFrame: Within 1 week of completing 8 weeks, from the beginning of intervention
Secondary outcomes:
measure: To compare the improvement in the sub domains(dissociated movements, grasp, protective extension and weight bearing) of QUEST score between the 2 groups
timeFrame: Within 1 week of completing 8 weeks, from the beginning of intervention
measure: Comparing the improvement in speed of movements between 2 groups
timeFrame: Within 1 week of completing 8 weeks,from the beginning of intervention
measure: Comparing the improvement in muscle strength between 2 groups
timeFrame: Within 1 week of completing 8 weeks,from the beginning of intervention
measure: Functional Magnetic Resonance Imaging(fMRI) in the 2 groups
timeFrame: Upto 1 week before starting mCIMT+ VRT program and within 1 week of completing 08 weeks, from the beginning of the intervention
measure: fMRI changes copared with clinical improvement in 2 groups before and after intervention
timeFrame: Upto 1 week before starting mCIMT+ VRT program and within 1 week of completing 08 weeks, from the beginning of the intervention
measure: DTI(Diffusion Tensor Imaging) changes compared with clinical improvement in 2 groups before and after intervention
timeFrame: Upto 1 week before starting mCIMT+ VRT program and within 1 week of completing 08 weeks, from the beginning of the intervention
measure: Diffusion Tensor Imaging changes in 2 groups
timeFrame: Upto 1 week before starting mCIMT+ VRT program and within 1 week of completing 08 weeks, from the beginning of the intervention
measure: Sustained improvement
timeFrame: Baseline and at 12 weeks of intervention
measure: Quality of life improvement
timeFrame: At the end of 8 weeks, from the beginning of intervention
measure: Compliance
timeFrame: At the end of 8 weeks, from the beginning of intervention
Other outcomes:
Locations:
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