Remote Ischemic Conditioning, Bimanual Skill Learning, and Corticospinal Excitability

NCT05355883 | Completed

• 1 other identifier: 21-001913
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

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 intensive bimanual skill training to enhance bimanual skill learning and to augment skill dependent plasticity in children with UCP.

Conditions

Unilateral Cerebral Palsy; Hemiplegic Cerebral Palsy; Remote Ischemic Conditioning

Keywords

Cerebral palsy; Bimanual coordination; Corticospinal excitability

Outcome Measures

Primary Outcomes (4)

• Change in Assisting Hand Assessment

  Assisting Hand Assessment assesses bimanual coordination and affected hand function. A 5-point change from pre- to post-intervention is considered a clinically meaningful improvement.

  Baseline and 1 week

• Change in Bimanual Task Performance

  The time (seconds) to complete each trial of cup stack, which will be averaged across three trials. This will be measured at visit 1 (pre-) and visit 7 (post-intervention). Smaller time to complete the task indicates better performance.

  Baseline and 1 week

• Change in Resting and Active Motor Thresholds

  The minimum intensity of the stimulator output required to produce an MEP of \> 50 μV will be determined using maximum-likelihood parameter estimation by a sequential testing (ML-PEST) algorithm from the lesioned and non-lesioned cortex. Greater reduction in resting and active motor threshold from pre- to post-intervention indicates greater corticospinal excitability.

  Baseline and 1 week

• Change in Stimulus-response curves

  Suprathreshold intensities of 110%, 120%, 130%, 140%, and 150% of resting motor threshold will be administered randomly on the lesioned and non-lesioned cortex. Greater motor evoked potential response at each of these intensities indicate greater corticospinal excitability.

  Baseline and 1 week

Secondary Outcomes (8)

• Change in Box and Blocks Test (BBT)

  Baseline and 1 week

• Change in Nine Hole Peg Test (NHPT)

  Baseline and 1 week

• Change in Jebsen Hand Function Test (JHFT)

  Baseline and 1 week

• Change in Balance performance

  Baseline and 1 week

• Change in Hand grip and pinch strength

  Baseline and 1 week

Study Arms (2)

Remote Ischemic Conditioning (RIC)

EXPERIMENTAL

RIC is achieved via blood pressure cuff inflation to at least 20 mmHg above systolic blood pressure to 250 mmHg on the more involved arm. RIC involves 5 cycles of 5 minutes blood pressure cuff inflation followed by alternating 5 minutes of cuff deflation and requires 45 minutes. RIC is performed on visits 2-6. Intervention * Hand Arm Bimanual Intensive Therapy (HABIT) * Bimanual cup stacking training * Balance training

Behavioral: Remote Ischemic Conditioning (RIC); Behavioral: Hand Arm Bimanual Intensive Therapy (HABIT); Behavioral: Bimanual Cup Stacking Training; Behavioral: Balance training

Sham Conditioning

SHAM COMPARATOR

Sham conditioning is achieved via blood pressure cuff inflation to 25 mmHg on the more involved arm. RIC involves 5 cycles of 5 minutes blood pressure cuff inflation followed by alternating 5 minutes of cuff deflation and requires 45 minutes. RIC is performed on visits 2-6. Intervention * Hand Arm Bimanual Intensive Therapy (HABIT) * Bimanual cup stacking training * Balance training

Behavioral: Sham conditioning; Behavioral: Hand Arm Bimanual Intensive Therapy (HABIT); Behavioral: Bimanual Cup Stacking Training; Behavioral: Balance training

Interventions

Remote Ischemic Conditioning (RIC) BEHAVIORAL

See descriptions under arm/group descriptions. RIC is delivered for 5 intervention visits. Visits 1 is the pre-training assessment visit, visits 2-6 are RIC plus training visits, visit 7 is a post-training assessment visit.

Also known as: Remote limb ischemic conditioning

Remote Ischemic Conditioning (RIC)

Sham conditioning BEHAVIORAL

See descriptions under arm/group descriptions. Sham conditioning is delivered for 5 intervention visits. Visits 1 is the pre-training assessment visit, visits 2-6 are RIC plus training visits, visit 7 is a post-training assessment visit.

Also known as: Sham

Sham Conditioning

Hand Arm Bimanual Intensive Therapy (HABIT) BEHAVIORAL

HABIT is a child-friendly, intensive intervention directed at improving bimanual coordination and function of the affected arm. The intervention employed in this study includes various age-appropriate fine and gross motor bimanual activities that will be delivered in a play context. Children practice bimanual activities for 6 hours per day, 5 days per week, for 1 week.

Also known as: Bimanual skill training

Remote Ischemic Conditioning (RIC); Sham Conditioning

Bimanual Cup Stacking Training BEHAVIORAL

Children practices bimanual cup stacking, 15 trials/day for 5 consecutive day.

Also known as: Cup stacking task

Remote Ischemic Conditioning (RIC); Sham Conditioning

Balance training BEHAVIORAL

All children undergo training on a balance board, learning to hold the board level with equal weight on each leg and using various bilateral upper extremity strategies. Participants perform the balance task for 15, 30-second trials per day at visits 2-6.

Remote Ischemic Conditioning (RIC); Sham Conditioning

Eligibility Criteria

• Age: 6 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children diagnosed with unilateral cerebral palsy, ages 6-16 years
• Manual Ability Classification System (MACS) levels I-III
• Ability to complete a stack of 3 cups in 2 minutes
• Mainstream in school and has sufficient cognition to follow the experiment instructions

You may not qualify if:

• Children with other developmental disabilities such as autism, developmental coordination disorders, etc.
• Children with absent active motor threshold
• Children with cognitive deficits or communication problem
• Children with known cardiorespiratory and vascular dysfunctions
• Children with metabolic disorders, neoplasm, hydrocephalus
• Children who are receiving other adjunct therapies such as rTMS and tDCS
• Children with seizures and on anti-seizure medications
• Children with metal implants and incompatible medical devices for MRI scans

Sponsors & Collaborators

• East Carolina University: lead

Study Sites (1)

Dept. of Physical Therapy, East Carolina University

Greenville, North Carolina, 27834, United States

Location

Related Publications (5)

• Surkar SM, Hoffman RM, Willett S, Flegle J, Harbourne R, Kurz MJ. Hand-Arm Bimanual Intensive Therapy Improves Prefrontal Cortex Activation in Children With Hemiplegic Cerebral Palsy. Pediatr Phys Ther. 2018 Apr;30(2):93-100. doi: 10.1097/PEP.0000000000000486.

  PMID: 29578992 BACKGROUND

• Dirnagl U, Becker K, Meisel A. Preconditioning and tolerance against cerebral ischaemia: from experimental strategies to clinical use. Lancet Neurol. 2009 Apr;8(4):398-412. doi: 10.1016/S1474-4422(09)70054-7.

  PMID: 19296922 BACKGROUND

• Gidday JM. Cerebral preconditioning and ischaemic tolerance. Nat Rev Neurosci. 2006 Jun;7(6):437-48. doi: 10.1038/nrn1927.

  PMID: 16715053 BACKGROUND

• Stetler RA, Leak RK, Gan Y, Li P, Zhang F, Hu X, Jing Z, Chen J, Zigmond MJ, Gao Y. Preconditioning provides neuroprotection in models of CNS disease: paradigms and clinical significance. Prog Neurobiol. 2014 Mar;114:58-83. doi: 10.1016/j.pneurobio.2013.11.005. Epub 2014 Jan 2.

  PMID: 24389580 BACKGROUND

• Kharbanda RK, Nielsen TT, Redington AN. Translation of remote ischaemic preconditioning into clinical practice. Lancet. 2009 Oct 31;374(9700):1557-65. doi: 10.1016/S0140-6736(09)61421-5.

  PMID: 19880021 BACKGROUND

MeSH Terms

Conditions

Cerebral Palsy

Interventions

salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Swati Surkar

  East Carolina University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants are masked to group assignment (RLIC vs. Sham conditioning) and the assessor will be masked to group assignment of the participants.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Double blinded, randomized controlled trial

Study Record Dates

• First Submitted: January 15, 2022
• First Posted: May 2, 2022
• Study Start: December 18, 2021
• Primary Completion: December 31, 2024
• Study Completion: May 30, 2025
• Last Updated: July 16, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF
• Time Frame: After publishing the results of the study
• Access Criteria: Data will be made available upon request to the principal investigator.

Locations

US (1)