Clinical trial NCT05777070: Effects of Remote Ischemic Conditioning on Bimanual Skill Learning and Corticospinal Excitability in Children With Unilateral Cerebral Palsy
Official title: Remote Ischemic Conditioning Combined With Bimanual Task Training to Enhance Bimanual Skill Learning and Corticospinal Excitability in Children With Unilateral Cerebral Palsy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Unilateral Cerebral Palsy
Lead sponsor: East Carolina University
Sponsor class: OTHER
First posted: 2023-03-20
Enrollment: 46
Sex: ALL
Minimum age (years): 8
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Triple blinded, randomized controlled trial
Primary purpose: TREATMENT

Brief summary: Unilateral cerebral palsy (UCP) is a leading cause of childhood disability. An early brain injury impairs the upper extremity function, bimanual coordination, and impacts the child's independence. The existing therapeutic interventions have higher training doses and modest effect sizes. Thus, there is a critical need to find an effective priming agent to enhance bimanual skill learning in children with UCP. This study aims to determine the effects of a novel priming agent, remote ischemic conditioning (RIC), when paired with bimanual skill training to enhance bimanual skill learning and to augment skill dependent plasticity in children with UCP.

Detailed description: Ischemic conditioning (IC) is a phenomenon of protecting the target organ from ischemia by directly exposing it to brief episodes of sublethal ischemia. RIC is a clinically feasible way of performing IC where episodes of ischemia and reperfusion are delivered with cyclic inflation and deflation of a blood pressure cuff on the arm or leg. Pre-clinical and preliminary clinical trials in humans show neuroprotective effects of RIC. Investigators prior work has shown that when paired with motor training, RIC enhances motor learning in healthy individuals. Based on these diversified benefits of RIC, the central hypothesis is that the multifactorial mechanisms of RIC can be harnessed as a priming agent to enhance motor learning and augment neuroplasticity in children with UCP. The Specific Aims are: 1) to determine the effects of RIC + training on bimanual skill learning and bimanual coordination, and 2) to determine the effects of RIC + training on corticospinal excitability in children with UCP. In this triple blind, randomized controlled trial, 46 children with UCP, ages 6-16 years will first undergo bimanual speed stack performance, functional upper extremity, and Transcranial Magnetic Stimulation assessments. Children will then undergo RIC/Sham conditioning plus training. Investigators will deliver RIC/sham conditioning via cyclic inflation and deflation of a pressure cuff on the paretic arm using a standard protocol. Training will involve 5 days (15 trials/day) of bimanual speed stack training for 5 days. The children will perform the same baseline assessments post-intervention. Investigators hypothesize that compared to sham conditioning + training, RIC + training will significantly enhance: 1) bimanual skill performance (decrease in movement time (sec) to complete bimanual speed stack task), 2) bimanual coordination and bimanual function (improvement in kinematic variables and increase in the Assisting Hand Assessment scores), 3) cortical excitability in the ipsilesional primary motor cortex (M1) (larger amplitude of motor evoked potentials and lower resting or active motor thresholds), and 4) reduce motor cortex inhibition (reduced short-interval intracortical inhibition and increase in intracortical facilitation in ipsilesional M1). The long-term goal is to develop effective interventions to improve function of children with UCP. Outcomes of this project will provide critical ingredients for designing Phase II trials that will determine the effects of RIC combined with different dose of intensive behavioral interventions to improve functional outcomes in children with UCP.

Eligibility criteria: Inclusion Criteria:

1. Children diagnosed with unilateral cerebral palsy (UCP)
2. Manual Ability Classification System (MACS) levels I-III
3. Ability to complete a stack of 3 cups in 1 minute
4. Mainstream in school

Exclusion Criteria:

1. Children with other developmental disabilities such as autism, attention deficit hyperactivity disorder, developmental coordination disorders, etc.
2. Children with absent active motor threshold
3. Children with known cardiorespiratory, vascular, and metabolic disorders
4. Children with neoplasm and hydrocephalus
5. Children who are currently receiving or received other adjunct therapies such as rTMS and tDCS in the past 6 months
6. Children with seizures within last 2 years and on anti-seizure medications
7. Children with metal implants and incompatible medical devices

Primary outcomes:
measure: Change in Bimanual Learning
timeFrame: Baseline and 1 week
measure: Change in Symmetric performance and tangential velocities
timeFrame: Baseline and 1 week
measure: Change in Resting Motor Threshold (rMT)
timeFrame: Baseline and 1 week
measure: Change in Active Motor Threshold (aMT)
timeFrame: Baseline and 1 week
Secondary outcomes:
measure: Change in Assisting Hand Assessment
timeFrame: Baseline and 1 week
measure: Change in Hand Trajectory
timeFrame: Baseline and 1 week
measure: Change in Temporal coupling (normalized movement overlap time)
timeFrame: Baseline and 1 week
measure: Change in total participation time of each hand
timeFrame: Baseline and 1 week
measure: Change in Goal Synchronization
timeFrame: Baseline and 1 week
measure: Change in total task duration
timeFrame: Baseline and 1 week
measure: Change in Stimulus response curve
timeFrame: Baseline and 1 week
measure: Change in Motor Evoked Potential (MEP) amplitude
timeFrame: Baseline and 1 week
measure: Change in Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF)
timeFrame: Baseline and 1 week
Other outcomes:
Locations:
city: Greenville
country: United States
facility: Dept. of Physical Therapy, East Carolina University
state: North Carolina
Study officials:
References:
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citation: Surkar SM, Bland MD, Mattlage AE, Chen L, Gidday JM, Lee JM, Hershey T, Lang CE. Effects of remote limb ischemic conditioning on muscle strength in healthy young adults: A randomized controlled trial. PLoS One. 2020 Feb 4;15(2):e0227263. doi: 10.1371/journal.pone.0227263. eCollection 2020.