Ischemic Conditioning to Enhance Function (I-C-FUN) in Children With Cerebral Palsy

Study Overview
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Brief Summary
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The purpose of this research study is to determine if remote limb ischemic conditioning (RLIC) can increase skeletal muscle power, enhance learning of motor (dynamic balance) task, and improve walking performance in children with cerebral palsy (CP).

Detailed Description
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Ischemic conditioning is a phenomenon in which an organ exposed to a controlled, short-term, local, sublethal ischemia protects from subsequent ischemia. Remote ischemic conditioning is another more practical approach where transient ischemia and reperfusion applied to a remote organ or tissue, protects other organs or tissues from further episodes of lethal ischemia/reperfusion injury. Remote limb ischemic conditioning (RLIC) is a clinically feasible way of performing remote ischemic conditioning where alternating, brief ischemia and reperfusion is delivered with cyclic inflation and deflation of a blood pressure cuff on the arm or leg. The overall goal of this research is to use ischemic conditioning to enhance muscle power, motor leaning, and mobility in children with CP. Our previous work demonstrated that when paired with strength training, RLIC improved muscle strength and activation in healthy, young adults and motor learning in healthy older adults. The current study extends that work to determine if RLIC enhances muscle power, dynamic balance, and walking performance in children with CP. This Phase II study will yield the necessary information to design and execute subsequent randomized controlled trials in children with CP as well as other neurological conditions.

Official Title
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Effects of Remote Limb Ischemic Conditioning to Enhance Muscle Power, Dynamic Balance, and Walking Performance in Children With Cerebral Palsy

Conditions
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Cerebral Palsy

Intervention / Treatment
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* Behavioral: RLIC
* Behavioral: Sham Conditioning
* Behavioral: Muscle Power training
* Behavioral: Balance training
* Behavioral: Treadmill Training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children diagnosed with unilateral or diplegia cerebral palsy (CP) Gross Motor Function Classification System (GMFCS) levels I-III Exclusion Criteria: Children with other developmental disabilities such as autism, developmental coordination disorders, etc. Children with cognitive deficits or communication problem Children with balance disorders such as vestibular disorders, posterior fossa tumors etc. Children with known cardiorespiratory dysfunctions Children who are receiving other adjunct therapies such as TMS, tDCS, vagal nerve stimulation Presence of lower extremity condition, injury, or surgery which could compromise conditioning and training Children with sickle cell disease

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

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
Interventional Model Description: Double blinded, randomized controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remote Limb Ischemic Conditioning (RLIC)<br>RLIC is achieved via blood pressure cuff inflation to at least 20 mmHg above systolic blood pressure to 200 mmHg on the more involved thigh. RLIC involves 5 cycles of 5 minutes blood pressure cuff inflation followed by alternating 5 minutes of cuff deflation and requires 45 minutes. RLIC is performed on visits 1-14. Interventions: Behavioral: RLIC Behavioral: Muscle power training Behavioral: Balance training Behavioral: Treadmill training | Behavioral: RLIC<br>* See descriptions under arm/group descriptions. RLIC is delivered for 14 visits. Visits 1-3 occur on consecutive work days and visits 4-14 occur on alternating week days.<br>* Other names: Remote Limb Ischemic Conditioning;Behavioral: Muscle Power training<br>* All participants undergo power training of the quadriceps muscles using unilateral and bilateral leg presses (Total Gym GTS, San Diego, CA), 3 times/week for 4 consecutive weeks (12 sessions). Power training will follow standard American College of Sports Medicine guidelines for frequency, intensity, progression etc. Power training is provided at visits 3-14.<br>* Other names: Quadriceps power training;Behavioral: Balance training<br>* All participants undergo training on a balance board, learning to hold the board level with equal weight on each leg. Participants perform the balance task for 15, 30-second trials per day at visits 3-14.<br>* Other names: Dynamic Stability Platform Training;Behavioral: Treadmill Training<br>* All participants will undergo short burst interval treadmill training using self-selected and fast walking speeds.<br>* Other names: Gait training;|
| Sham Comparator: Sham Conditioning<br>Sham conditioning is achieved via blood pressure cuff inflation to 25 mmHg on the more involved thigh. Sham involves 5 cycles of 5 minutes blood pressure cuff inflation followed by alternating 5 minutes of cuff deflation and requires 45 minutes. Sham conditioning is performed on visits 1-14. Interventions: Behavioral: RLIC Behavioral: Muscle power training Behavioral: Balance training Behavioral: Treadmill training | Behavioral: Sham Conditioning<br>* See descriptions under arm/group descriptions. Sham conditioning is delivered for 14 visits. Visits 1-3 occur on consecutive work days and visits 4-14 occur on alternating week days.<br>* Other names: Sham;Behavioral: Muscle Power training<br>* All participants undergo power training of the quadriceps muscles using unilateral and bilateral leg presses (Total Gym GTS, San Diego, CA), 3 times/week for 4 consecutive weeks (12 sessions). Power training will follow standard American College of Sports Medicine guidelines for frequency, intensity, progression etc. Power training is provided at visits 3-14.<br>* Other names: Quadriceps power training;Behavioral: Balance training<br>* All participants undergo training on a balance board, learning to hold the board level with equal weight on each leg. Participants perform the balance task for 15, 30-second trials per day at visits 3-14.<br>* Other names: Dynamic Stability Platform Training;Behavioral: Treadmill Training<br>* All participants will undergo short burst interval treadmill training using self-selected and fast walking speeds.<br>* Other names: Gait training;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Peak knee extension power | Power is defined as the ability to exert a maximum force in short amount of time (speed) while performing knee extension. Bilateral quadriceps power will be measured using Humac Norm Isokinetic testing device (Computer Sports Medicine Inc, Stoughton, MA). | Pre-intervention to 1 month post-intervention follow-up | 
| Change in Balance Score | The average amount of time in seconds that a participant maintains the stability platform within ±5° of horizontal position during 15 trials of 30 seconds each. The total score will range between 0-30 seconds. Higher balance score indicates better balance performance. | Pre-intervention to 1 month post-intervention follow-up | 
| Change in Walking Speed | Self-selected and fast walking speeds will be measured using 10-meter walk test. | Pre-intervention to 1 month post-intervention follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quadriceps Electromyography | While performing the isokinetic power testing, the electromyography (EMG) data will be recorded simultaneously. The EMG data will be used to quantify the electrical amplitude of quadriceps muscle. | Pre-intervention to 1 month post-intervention follow-up | 
| Gait Analysis | Lower extremity walking kinematics and kinetics will be measured using 10-camera motion analysis system (Qualisys Inc., Gothenburg, Sweden). Specific kinematic variables are hip, knee, and ankle joint torques. Kinetic variables are peak hip, knee, and ankle sagittal plane joint moments. | Pre-intervention to 1 month post-intervention follow-up | 
| Lower limb activity | Lower extremity activity will be measured using accelerometers (Actigraphs) worn on bilateral ankles for 24 hours. Specific accelerometry variable will be number of steps. | Pre-intervention to 1 month post-intervention follow-up |