search
Back to results

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

Primary Purpose

Unilateral Cerebral Palsy

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Bimanual Cup Stacking Training
Sponsored by
East Carolina University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Unilateral Cerebral Palsy

Eligibility Criteria

8 Years - 16 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 Exclusion Criteria: 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

Sites / Locations

  • Dept. of Physical Therapy, East Carolina UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Remote Ischemic Conditioning (RIC)

Sham conditioning

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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).
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.
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.
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.

Secondary Outcome Measures

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.
Change in Hand Trajectory
Hand trajectory is defined as the resultant 3D path length between the starting position and task completion.
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
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.
Change in Goal Synchronization
Goal synchronization is defined as a time lag between the initiation of the affected compared to the unaffected arm
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.
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.
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.
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.

Full Information

First Posted
March 6, 2023
Last Updated
March 19, 2023
Sponsor
East Carolina University
search

1. Study Identification

Unique Protocol Identification Number
NCT05777070
Brief Title
Effects of Remote Ischemic Conditioning on Bimanual Skill Learning and Corticospinal Excitability in Children With Unilateral Cerebral Palsy
Acronym
RIC
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 7, 2022 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
August 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
East Carolina University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Unilateral Cerebral Palsy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Triple blinded, randomized controlled trial
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
Participants are masked to group assignments, investigators are masked to assessments, and outcomes assessors are masked to intervention groups
Allocation
Randomized
Enrollment
46 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Remote Ischemic Conditioning (RIC)
Arm Type
Experimental
Arm Description
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.
Arm Title
Sham conditioning
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Bimanual Cup Stacking Training
Other Intervention Name(s)
Remote limb ischemic conditioning, Sham conditioning
Intervention Description
Children practices bimanual cup stacking, 15 trials/day for 5 consecutive days
Primary Outcome Measure Information:
Title
Change in Bimanual Learning
Description
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).
Time Frame
Baseline and 1 week
Title
Change in Symmetric performance and tangential velocities
Description
Symmetric performance is characterized as a time-lag between the affected and less affected arm during movement onset and task completion.
Time Frame
Baseline and 1 week
Title
Change in Resting Motor Threshold (rMT)
Description
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.
Time Frame
Baseline and 1 week
Title
Change in Active Motor Threshold (aMT)
Description
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.
Time Frame
Baseline and 1 week
Secondary Outcome Measure Information:
Title
Change in Assisting Hand Assessment
Description
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.
Time Frame
Baseline and 1 week
Title
Change in Hand Trajectory
Description
Hand trajectory is defined as the resultant 3D path length between the starting position and task completion.
Time Frame
Baseline and 1 week
Title
Change in Temporal coupling (normalized movement overlap time)
Description
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
Time Frame
Baseline and 1 week
Title
Change in total participation time of each hand
Description
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.
Time Frame
Baseline and 1 week
Title
Change in Goal Synchronization
Description
Goal synchronization is defined as a time lag between the initiation of the affected compared to the unaffected arm
Time Frame
Baseline and 1 week
Title
Change in total task duration
Description
Total task duration is defined as the duration from movement onset until the criteria for task completion is reached with both hands.
Time Frame
Baseline and 1 week
Title
Change in Stimulus response curve
Description
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.
Time Frame
Baseline and 1 week
Title
Change in Motor Evoked Potential (MEP) amplitude
Description
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.
Time Frame
Baseline and 1 week
Title
Change in Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF)
Description
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.
Time Frame
Baseline and 1 week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Swati Surkar, PT, PhD
Phone
2527446244
Email
surkars19@ecu.edu
Facility Information:
Facility Name
Dept. of Physical Therapy, East Carolina University
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Swati Surkar
Phone
402-714-2640
Email
surkars19@ecu.edu

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Data will be shared on NIH figshare network and will be made available on request.
Citations:
PubMed Identifier
19880021
Citation
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.
Results Reference
background
PubMed Identifier
19296922
Citation
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.
Results Reference
result
PubMed Identifier
16715053
Citation
Gidday JM. Cerebral preconditioning and ischaemic tolerance. Nat Rev Neurosci. 2006 Jun;7(6):437-48. doi: 10.1038/nrn1927.
Results Reference
result
PubMed Identifier
24389580
Citation
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.
Results Reference
result
PubMed Identifier
30915491
Citation
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.
Results Reference
result
PubMed Identifier
30088217
Citation
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.
Results Reference
result
PubMed Identifier
32017777
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.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs