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

July 9, 2025 updated by: Swati Manoharrao Surkar, East Carolina University

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
51

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • North Carolina
      • Greenville, North Carolina, United States, 27834
        • Dept. of Physical Therapy, East Carolina University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

8 years to 16 years (Child)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Remote Ischemic Conditioning (RIC)
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
Children practices bimanual cup stacking, 15 trials/day for 5 consecutive days
Other Names:
  • Remote limb ischemic conditioning
  • Sham conditioning
Sham Comparator: Sham conditioning
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
Children practices bimanual cup stacking, 15 trials/day for 5 consecutive days
Other Names:
  • Remote limb ischemic conditioning
  • Sham conditioning

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Bimanual Learning
Time Frame: Baseline and 1 week
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
Time Frame: Baseline and 1 week
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)
Time Frame: Baseline and 1 week
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)
Time Frame: Baseline and 1 week
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Assisting Hand Assessment
Time Frame: Baseline and 1 week
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 Hand Trajectory
Time Frame: Baseline and 1 week
Hand trajectory is defined as the resultant 3D path length between the starting position and task completion.
Baseline and 1 week
Change in Temporal coupling (normalized movement overlap time)
Time Frame: Baseline and 1 week
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
Baseline and 1 week
Change in total participation time of each hand
Time Frame: Baseline and 1 week
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.
Baseline and 1 week
Change in Goal Synchronization
Time Frame: Baseline and 1 week
Goal synchronization is defined as a time lag between the initiation of the affected compared to the unaffected arm
Baseline and 1 week
Change in total task duration
Time Frame: Baseline and 1 week
Total task duration is defined as the duration from movement onset until the criteria for task completion is reached with both hands.
Baseline and 1 week
Change in Stimulus response curve
Time Frame: Baseline and 1 week
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.
Baseline and 1 week
Change in Motor Evoked Potential (MEP) amplitude
Time Frame: Baseline and 1 week
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.
Baseline and 1 week
Change in Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF)
Time Frame: Baseline and 1 week
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.
Baseline and 1 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
East Carolina University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

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Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 7, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 6, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 20, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 14, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 9, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MS4_UMCIRB 21-001913

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Data will be shared on NIH figshare network and will be made available on request.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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