Ischemic Conditioning to Enhance Function (I-C-FUN) in Children With Cerebral Palsy

NCT ID: NCT04598711

Last Updated: 2023-03-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-15

Study Completion Date

2022-12-30

Brief Summary

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The purpose of this research study is to determine if remote limb ischemic conditioning (RLIC) can increase skeletal muscle power, enhance learning of motor (dynamic balance) task, and improve walking performance in children with cerebral palsy (CP).

Detailed Description

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Ischemic conditioning is a phenomenon in which an organ exposed to a controlled, short-term, local, sublethal ischemia protects from subsequent ischemia. Remote ischemic conditioning is another more practical approach where transient ischemia and reperfusion applied to a remote organ or tissue, protects other organs or tissues from further episodes of lethal ischemia/reperfusion injury. Remote limb ischemic conditioning (RLIC) is a clinically feasible way of performing remote ischemic conditioning where alternating, brief ischemia and reperfusion is delivered with cyclic inflation and deflation of a blood pressure cuff on the arm or leg.

The overall goal of this research is to use ischemic conditioning to enhance muscle power, motor leaning, and mobility in children with CP. Our previous work demonstrated that when paired with strength training, RLIC improved muscle strength and activation in healthy, young adults and motor learning in healthy older adults. The current study extends that work to determine if RLIC enhances muscle power, dynamic balance, and walking performance in children with CP. This Phase II study will yield the necessary information to design and execute subsequent randomized controlled trials in children with CP as well as other neurological conditions.

Conditions

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Cerebral Palsy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Double blinded, randomized controlled trial
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors
Participants are masked to group assignment (RLIC vs. Sham conditioning) and the assessor will be masked to group assignment of the participants.

Study Groups

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Remote Limb Ischemic Conditioning (RLIC)

RLIC is achieved via blood pressure cuff inflation to at least 20 mmHg above systolic blood pressure to 200 mmHg on the more involved thigh. RLIC involves 5 cycles of 5 minutes blood pressure cuff inflation followed by alternating 5 minutes of cuff deflation and requires 45 minutes. RLIC is performed on visits 1-14.

Interventions:

* Behavioral: RLIC
* Behavioral: Muscle power training
* Behavioral: Balance training
* Behavioral: Treadmill training

Group Type EXPERIMENTAL

RLIC

Intervention Type BEHAVIORAL

See descriptions under arm/group descriptions. RLIC is delivered for 14 visits. Visits 1-3 occur on consecutive work days and visits 4-14 occur on alternating week days.

Muscle Power training

Intervention Type BEHAVIORAL

All participants undergo power training of the quadriceps muscles using unilateral and bilateral leg presses (Total Gym GTS, San Diego, CA), 3 times/week for 4 consecutive weeks (12 sessions). Power training will follow standard American College of Sports Medicine guidelines for frequency, intensity, progression etc. Power training is provided at visits 3-14.

Balance training

Intervention Type BEHAVIORAL

All participants undergo training on a balance board, learning to hold the board level with equal weight on each leg. Participants perform the balance task for 15, 30-second trials per day at visits 3-14.

Treadmill Training

Intervention Type BEHAVIORAL

All participants will undergo short burst interval treadmill training using self-selected and fast walking speeds.

Sham Conditioning

Sham conditioning is achieved via blood pressure cuff inflation to 25 mmHg on the more involved thigh. Sham involves 5 cycles of 5 minutes blood pressure cuff inflation followed by alternating 5 minutes of cuff deflation and requires 45 minutes. Sham conditioning is performed on visits 1-14.

Interventions:

* Behavioral: RLIC
* Behavioral: Muscle power training
* Behavioral: Balance training
* Behavioral: Treadmill training

Group Type SHAM_COMPARATOR

Sham Conditioning

Intervention Type BEHAVIORAL

See descriptions under arm/group descriptions. Sham conditioning is delivered for 14 visits. Visits 1-3 occur on consecutive work days and visits 4-14 occur on alternating week days.

Muscle Power training

Intervention Type BEHAVIORAL

All participants undergo power training of the quadriceps muscles using unilateral and bilateral leg presses (Total Gym GTS, San Diego, CA), 3 times/week for 4 consecutive weeks (12 sessions). Power training will follow standard American College of Sports Medicine guidelines for frequency, intensity, progression etc. Power training is provided at visits 3-14.

Balance training

Intervention Type BEHAVIORAL

All participants undergo training on a balance board, learning to hold the board level with equal weight on each leg. Participants perform the balance task for 15, 30-second trials per day at visits 3-14.

Treadmill Training

Intervention Type BEHAVIORAL

All participants will undergo short burst interval treadmill training using self-selected and fast walking speeds.

Interventions

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RLIC

See descriptions under arm/group descriptions. RLIC is delivered for 14 visits. Visits 1-3 occur on consecutive work days and visits 4-14 occur on alternating week days.

Intervention Type BEHAVIORAL

Sham Conditioning

See descriptions under arm/group descriptions. Sham conditioning is delivered for 14 visits. Visits 1-3 occur on consecutive work days and visits 4-14 occur on alternating week days.

Intervention Type BEHAVIORAL

Muscle Power training

All participants undergo power training of the quadriceps muscles using unilateral and bilateral leg presses (Total Gym GTS, San Diego, CA), 3 times/week for 4 consecutive weeks (12 sessions). Power training will follow standard American College of Sports Medicine guidelines for frequency, intensity, progression etc. Power training is provided at visits 3-14.

Intervention Type BEHAVIORAL

Balance training

All participants undergo training on a balance board, learning to hold the board level with equal weight on each leg. Participants perform the balance task for 15, 30-second trials per day at visits 3-14.

Intervention Type BEHAVIORAL

Treadmill Training

All participants will undergo short burst interval treadmill training using self-selected and fast walking speeds.

Intervention Type BEHAVIORAL

Other Intervention Names

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Remote Limb Ischemic Conditioning Sham Quadriceps power training Dynamic Stability Platform Training Gait training

Eligibility Criteria

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Inclusion Criteria

1. Children diagnosed with unilateral or diplegia cerebral palsy (CP)
2. Gross Motor Function Classification System (GMFCS) levels I-III

Exclusion Criteria

1. Children with other developmental disabilities such as autism, developmental coordination disorders, etc.
2. Children with cognitive deficits or communication problem
3. Children with balance disorders such as vestibular disorders, posterior fossa tumors etc.
4. Children with known cardiorespiratory dysfunctions
5. Children who are receiving other adjunct therapies such as TMS, tDCS, vagal nerve stimulation
6. Presence of lower extremity condition, injury, or surgery which could compromise conditioning and training
7. Children with sickle cell disease
Minimum Eligible Age

6 Years

Maximum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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East Carolina University

OTHER

Sponsor Role lead

Responsible Party

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Swati Manoharrao Surkar

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Swati M Surkar, PT, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistant Professor, East Carolina University

Locations

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East Carolina University

Greenville, North Carolina, United States

Site Status

Countries

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United States

References

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

Reference Type BACKGROUND
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Saxena P, Newman MA, Shehatha JS, Redington AN, Konstantinov IE. Remote ischemic conditioning: evolution of the concept, mechanisms, and clinical application. J Card Surg. 2010 Jan-Feb;25(1):127-34. doi: 10.1111/j.1540-8191.2009.00820.x. Epub 2009 Jun 22.

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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.

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Meng R, Asmaro K, Meng L, Liu Y, Ma C, Xi C, Li G, Ren C, Luo Y, Ling F, Jia J, Hua Y, Wang X, Ding Y, Lo EH, Ji X. Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology. 2012 Oct 30;79(18):1853-61. doi: 10.1212/WNL.0b013e318271f76a. Epub 2012 Oct 3.

Reference Type BACKGROUND
PMID: 23035060 (View on PubMed)

Ali ZA, Callaghan CJ, Lim E, Ali AA, Nouraei SA, Akthar AM, Boyle JR, Varty K, Kharbanda RK, Dutka DP, Gaunt ME. Remote ischemic preconditioning reduces myocardial and renal injury after elective abdominal aortic aneurysm repair: a randomized controlled trial. Circulation. 2007 Sep 11;116(11 Suppl):I98-105. doi: 10.1161/circulationaha.106.679167.

Reference Type BACKGROUND
PMID: 17846333 (View on PubMed)

Liu ZJ, Chen C, Li XR, Ran YY, Xu T, Zhang Y, Geng XK, Zhang Y, Du HS, Leak RK, Ji XM, Hu XM. Remote Ischemic Preconditioning-Mediated Neuroprotection against Stroke is Associated with Significant Alterations in Peripheral Immune Responses. CNS Neurosci Ther. 2016 Jan;22(1):43-52. doi: 10.1111/cns.12448. Epub 2015 Sep 19.

Reference Type BACKGROUND
PMID: 26384716 (View on PubMed)

Jean-St-Michel E, Manlhiot C, Li J, Tropak M, Michelsen MM, Schmidt MR, McCrindle BW, Wells GD, Redington AN. Remote preconditioning improves maximal performance in highly trained athletes. Med Sci Sports Exerc. 2011 Jul;43(7):1280-6. doi: 10.1249/MSS.0b013e318206845d.

Reference Type BACKGROUND
PMID: 21131871 (View on PubMed)

Kjeld T, Rasmussen MR, Jattu T, Nielsen HB, Secher NH. Ischemic preconditioning of one forearm enhances static and dynamic apnea. Med Sci Sports Exerc. 2014 Jan;46(1):151-5. doi: 10.1249/MSS.0b013e3182a4090a.

Reference Type BACKGROUND
PMID: 23846166 (View on PubMed)

de Groot PC, Thijssen DH, Sanchez M, Ellenkamp R, Hopman MT. Ischemic preconditioning improves maximal performance in humans. Eur J Appl Physiol. 2010 Jan;108(1):141-6. doi: 10.1007/s00421-009-1195-2. Epub 2009 Sep 18.

Reference Type BACKGROUND
PMID: 19760432 (View on PubMed)

Bailey TG, Jones H, Gregson W, Atkinson G, Cable NT, Thijssen DH. Effect of ischemic preconditioning on lactate accumulation and running performance. Med Sci Sports Exerc. 2012 Nov;44(11):2084-9. doi: 10.1249/MSS.0b013e318262cb17.

Reference Type BACKGROUND
PMID: 22843115 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32017777 (View on PubMed)

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.

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Damiano DL, Laws E, Carmines DV, Abel MF. Relationship of spasticity to knee angular velocity and motion during gait in cerebral palsy. Gait Posture. 2006 Jan;23(1):1-8. doi: 10.1016/j.gaitpost.2004.10.007. Epub 2005 Jan 7.

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Steele KM, Damiano DL, Eek MN, Unger M, Delp SL. Characteristics associated with improved knee extension after strength training for individuals with cerebral palsy and crouch gait. J Pediatr Rehabil Med. 2012;5(2):99-106. doi: 10.3233/PRM-2012-0201.

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Steele KM, van der Krogt MM, Schwartz MH, Delp SL. How much muscle strength is required to walk in a crouch gait? J Biomech. 2012 Oct 11;45(15):2564-9. doi: 10.1016/j.jbiomech.2012.07.028. Epub 2012 Sep 5.

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Hyngstrom AS, Murphy SA, Nguyen J, Schmit BD, Negro F, Gutterman DD, Durand MJ. Ischemic conditioning increases strength and volitional activation of paretic muscle in chronic stroke: a pilot study. J Appl Physiol (1985). 2018 May 1;124(5):1140-1147. doi: 10.1152/japplphysiol.01072.2017. Epub 2018 Feb 8.

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Cherry-Allen KM, Gidday JM, Lee JM, Hershey T, Lang CE. Remote limb ischemic conditioning enhances motor learning in healthy humans. J Neurophysiol. 2015 Jun 1;113(10):3708-19. doi: 10.1152/jn.01028.2014. Epub 2015 Apr 1.

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Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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19-003232

Identifier Type: -

Identifier Source: org_study_id

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