Effects of Remote Ischemic Conditioning on Bimanual Skill Learning and Corticospinal Excitability in Children With Unilateral Cerebral Palsy

NCT05777070 | Completed DMC

• 1 other identifier: MS4_UMCIRB 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 bimanual skill training to enhance bimanual skill learning and to augment skill dependent plasticity in children with UCP.

Conditions

Unilateral Cerebral Palsy

Outcome Measures

Primary Outcomes (4)

• Change in Bimanual Learning

  The time (seconds) to complete each trial of cup stack, which will be averaged across nine trials. This will be measured at visit 1 (pre-) and visit 7 (post-intervention).

  Baseline and 1 week

• Change in Symmetric performance and tangential velocities

  Symmetric performance is characterized as a time-lag between the affected and less affected arm during movement onset and task completion.

  Baseline and 1 week

• Change in Resting Motor Threshold (rMT)

  The rMT is the stimulator output required to produce a motor evoked potential (MEP) of \> 50 μV in at least 5/10 trials in FDI muscle.

  Baseline and 1 week

• Change in Active Motor Threshold (aMT)

  The aMT is the stimulator output required to produce a motor evoked potential (MEP) of \> 200 μV in FDI muscle during 30% of MVIC of FDI muscle using a pinch grip. aMT is a measure of motor cortex excitability.

  Baseline and 1 week

Secondary Outcomes (9)

• Change in Assisting Hand Assessment

  Baseline and 1 week

• Change in Hand Trajectory

  Baseline and 1 week

• Change in Temporal coupling (normalized movement overlap time)

  Baseline and 1 week

• Change in total participation time of each hand

  Baseline and 1 week

• Change in Goal Synchronization

  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 1-7.

Behavioral: Bimanual Cup Stacking 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 1-7.

Behavioral: Bimanual Cup Stacking Training

Interventions

Bimanual Cup Stacking Training BEHAVIORAL

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

Also known as: Remote limb ischemic conditioning, Sham conditioning

Remote Ischemic Conditioning (RIC); Sham conditioning

Eligibility Criteria

• Age: 8 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

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

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 (8)

• 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

• 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 RESULT

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

  PMID: 16715053 RESULT

• 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 RESULT

• Mattlage AE, Sutter EN, Bland MD, Surkar SM, Gidday JM, Lee JM, Hershey T, Chen L, Lang CE. Dose of remote limb ischemic conditioning for enhancing learning in healthy young adults. Exp Brain Res. 2019 Jun;237(6):1493-1502. doi: 10.1007/s00221-019-05519-w. Epub 2019 Mar 26.

  PMID: 30915491 RESULT

• Sutter EN, Mattlage AE, Bland MD, Cherry-Allen KM, Harrison E, Surkar SM, Gidday JM, Chen L, Hershey T, Lee JM, Lang CE. Remote Limb Ischemic Conditioning and Motor Learning: Evaluation of Factors Influencing Response in Older Adults. Transl Stroke Res. 2019 Aug;10(4):362-371. doi: 10.1007/s12975-018-0653-8. Epub 2018 Aug 7.

  PMID: 30088217 RESULT

• 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.

  PMID: 32017777 RESULT

• Surkar SM, Willson JD, Cassidy JM, Kantak S, Patterson CG. Remote ischaemic conditioning combined with bimanual task training to enhance bimanual skill learning and corticospinal excitability in children with unilateral cerebral palsy: a study protocol of a single centre, phase II randomised controlled trial. BMJ Open. 2023 Sep 28;13(9):e076881. doi: 10.1136/bmjopen-2023-076881.

  PMID: 37770277 DERIVED

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants are masked to group assignments, investigators are masked to assessments, and outcomes assessors are masked to intervention groups
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Triple blinded, randomized controlled trial

Study Record Dates

• First Submitted: March 6, 2023
• First Posted: March 20, 2023
• Study Start: November 7, 2022
• Primary Completion: December 31, 2024
• Study Completion: May 30, 2025
• Last Updated: July 14, 2025

Record last verified: 2025-07

Locations

US (1)