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Unilateral Cerebral PalsyRICNCT05777070

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

A study testing Bimanual Cup Stacking Training in people with Unilateral Cerebral Palsy, run by East Carolina University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 8 to 16 years
Conditions the study is for
Unilateral Cerebral Palsy
What is being tested?
Bimanual Cup Stacking Training
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
51 participants
Where
1 siteUnited States
Study dates
7 Nov 2022to 30 May 2025
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 8 to 16 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Dept. of Physical Therapy, East Carolina University

    Greenville, North Carolina, 27834

Other trials in United States

About this study

Official title: Remote Ischemic Conditioning Combined With Bimanual Task Training to Enhance Bimanual Skill Learning and Corticospinal Excitability in Children With Unilateral Cerebral Palsy

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.

Read the 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.

Being tested
Bimanual Cup Stacking Training

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bimanual Cup Stacking TrainingBehavioural

    Also called Remote limb ischemic conditioning, Sham conditioning

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

Study groups in NCT05777070
Study groupRoleWhat they receive
Remote Ischemic Conditioning (RIC)ExperimentalRIC 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.
Receives: Behavioral: Bimanual Cup Stacking Training
Sham conditioningSham comparatorSham 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.
Receives: Behavioral: Bimanual Cup Stacking Training

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Baseline and 1 week

  2. 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.

    Measured: Baseline and 1 week

  3. 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.

    Measured: Baseline and 1 week

  4. 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.

    Measured: Baseline and 1 week

Secondary outcomes (9)
  1. 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.

    Measured: Baseline and 1 week

  2. Change in Hand Trajectory

    Hand trajectory is defined as the resultant 3D path length between the starting position and task completion.

    Measured: Baseline and 1 week

  3. Change in Temporal coupling (normalized movement overlap time)

    Normalized movement overlap time is calculated as the percentage of total task completion time that both hands are participating in the stacking sequence during bimanual coordination task

    Measured: Baseline and 1 week

  4. Change in total participation time of each hand

    Total participation time is calculated as the total amount of time the affected and the less affected hand participate in bimanual coordination task. A hand will be considered as participating in the task any time the wrist marker tangential velocity remains over 2.0 cm/s for at least 100 ms.

    Measured: Baseline and 1 week

  5. Change in Goal Synchronization

    Goal synchronization is defined as a time lag between the initiation of the affected compared to the unaffected arm

    Measured: Baseline and 1 week

  6. Change in total task duration

    Total task duration is defined as the duration from movement onset until the criteria for task completion is reached with both hands.

    Measured: Baseline and 1 week

  7. Change in Stimulus response curve

    stimulus-response curves will be constructed for the ipsilesional as well as contralesional M1 at intensities of 90%, 100%, 110%, 120%, 130%, 140%, and 150% of rMT (10 stimuli per intensity in random order). The peak-to-peak amplitude of MEPs and area under the curve of resultant MEPs to these intensities will be calculated.

    Measured: Baseline and 1 week

  8. Change in Motor Evoked Potential (MEP) amplitude

    The peak-to-peak amplitude of the EMG response from the affected as well as unaffected FDI muscle while stimulating the ipsilesional as well as contralesional motor cortex will be recorded at 100% rMT and averaged across 10 single-pulse trials. MEP amplitude indicates the strength of motor response to TMS.

    Measured: Baseline and 1 week

  9. Change in Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF)

    SICI and ICF will be obtained by applying a conditioning stimulus at 80% rMT intensity or AMT intensity followed by a test stimulus at 120% rMT intensity over the hot spot. The interstimulus interval between the conditioning and test stimulus will be 3 ms for obtaining measures of SICI and 15 ms for obtaining ICF.

    Measured: Baseline and 1 week

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2023
  2. Study start7 Nov 2022
  3. Primary completion31 Dec 2024
  4. Study completion30 May 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Triple blinded, randomized controlled trial
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05777070
Sponsor's protocol ID
MS4_UMCIRB 21-001913
Acronym
RIC
Status last verified
Jul 2025
First submitted
6 Mar 2023
Last updated
14 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: Data will be shared on NIH figshare network and will be made available on request.

Publications

  • 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.

    PubMed 19880021
  • 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.

    PubMed 19296922
  • Gidday JM. Cerebral preconditioning and ischaemic tolerance. Nat Rev Neurosci. 2006 Jun;7(6):437-48. doi: 10.1038/nrn1927.

    PubMed 16715053
  • 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.

    PubMed 24389580
  • 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.

    PubMed 30915491
  • 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.

    PubMed 30088217
  • 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.

    PubMed 32017777
  • 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.

    PubMed 37770277

Questions about this trial

What is this clinical trial studying?

A study testing Bimanual Cup Stacking Training in people with Unilateral Cerebral Palsy, run by East Carolina University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Bimanual Learning (time frame: Baseline and 1 week). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05777070, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2025.

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