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

NCT04598711 | Completed DMC

• 1 other identifier: 19-003232
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Cerebral Palsy

Outcome Measures

Primary Outcomes (3)

• Change in Peak knee extension power

  Power is defined as the ability to exert a maximum force in short amount of time (speed) while performing knee extension. Bilateral quadriceps power will be measured using Humac Norm Isokinetic testing device (Computer Sports Medicine Inc, Stoughton, MA).

  Pre-intervention to 1 month post-intervention follow-up

• Change in Balance Score

  The average amount of time in seconds that a participant maintains the stability platform within ±5° of horizontal position during 15 trials of 30 seconds each. The total score will range between 0-30 seconds. Higher balance score indicates better balance performance.

  Pre-intervention to 1 month post-intervention follow-up

• Change in Walking Speed

  Self-selected and fast walking speeds will be measured using 10-meter walk test.

  Pre-intervention to 1 month post-intervention follow-up

Secondary Outcomes (3)

• Quadriceps Electromyography

  Pre-intervention to 1 month post-intervention follow-up

• Gait Analysis

  Pre-intervention to 1 month post-intervention follow-up

• Lower limb activity

  Pre-intervention to 1 month post-intervention follow-up

Study Arms (2)

Remote Limb Ischemic Conditioning (RLIC)

EXPERIMENTAL

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

Behavioral: RLIC; Behavioral: Muscle Power training; Behavioral: Balance training; Behavioral: Treadmill Training

Sham Conditioning

SHAM COMPARATOR

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

Behavioral: Sham Conditioning; Behavioral: Muscle Power training; Behavioral: Balance training; Behavioral: Treadmill Training

Interventions

RLIC 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.

Also known as: Remote Limb Ischemic Conditioning

Remote Limb Ischemic Conditioning (RLIC)

Sham Conditioning 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.

Also known as: Sham

Sham Conditioning

Muscle Power training 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.

Also known as: Quadriceps power training

Remote Limb Ischemic Conditioning (RLIC); Sham Conditioning

Balance training 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.

Also known as: Dynamic Stability Platform Training

Remote Limb Ischemic Conditioning (RLIC); Sham Conditioning

Treadmill Training BEHAVIORAL

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

Also known as: Gait training

Remote Limb Ischemic Conditioning (RLIC); Sham Conditioning

Eligibility Criteria

• Age: 6 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• East Carolina University: lead

Study Sites (1)

East Carolina University

Greenville, North Carolina, 27834, United States

Location

Related Publications (21)

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

  PMID: 16715053 BACKGROUND

• 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.

  PMID: 19549044 BACKGROUND

• 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

• Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E, Ashley E, Vichare S, Di Salvo C, Kolvekar S, Hayward M, Keogh B, MacAllister RJ, Yellon DM. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet. 2007 Aug 18;370(9587):575-9. doi: 10.1016/S0140-6736(07)61296-3.

  PMID: 17707752 BACKGROUND

• Botker HE, Kharbanda R, Schmidt MR, Bottcher M, Kaltoft AK, Terkelsen CJ, Munk K, Andersen NH, Hansen TM, Trautner S, Lassen JF, Christiansen EH, Krusell LR, Kristensen SD, Thuesen L, Nielsen SS, Rehling M, Sorensen HT, Redington AN, Nielsen TT. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet. 2010 Feb 27;375(9716):727-34. doi: 10.1016/S0140-6736(09)62001-8.

  PMID: 20189026 BACKGROUND

• 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.

  PMID: 23035060 BACKGROUND

• 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.

  PMID: 17846333 BACKGROUND

• 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.

  PMID: 26384716 BACKGROUND

• 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.

  PMID: 21131871 BACKGROUND

• 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.

  PMID: 23846166 BACKGROUND

• 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.

  PMID: 19760432 BACKGROUND

• 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.

  PMID: 22843115 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 16311188 BACKGROUND

• 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.

  PMID: 22699100 BACKGROUND

• 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.

  PMID: 22959837 BACKGROUND

• Moreau NG, Holthaus K, Marlow N. Differential adaptations of muscle architecture to high-velocity versus traditional strength training in cerebral palsy. Neurorehabil Neural Repair. 2013 May;27(4):325-34. doi: 10.1177/1545968312469834. Epub 2013 Jan 4.

  PMID: 23292847 BACKGROUND

• 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.

  PMID: 29420152 BACKGROUND

• 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.

  PMID: 25867743 BACKGROUND

• Christie A, Kamen G. Short-term training adaptations in maximal motor unit firing rates and afterhyperpolarization duration. Muscle Nerve. 2010 May;41(5):651-60. doi: 10.1002/mus.21539.

  PMID: 19941348 BACKGROUND

MeSH Terms

Conditions

Cerebral Palsy

Interventions

salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Swati M Surkar, PT, PhD

  Assistant Professor, East Carolina University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants are masked to group assignment (RLIC vs. Sham conditioning) and the assessor will be masked to group assignment of the participants.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Double blinded, randomized controlled trial

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: October 22, 2020
• Study Start: June 15, 2021
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2022
• Last Updated: March 13, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be available soon after the completion of the study.
• Access Criteria: Contact Dr. Surkar

Locations

US (1)