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

Cerebral Palsy Clinical Trial

— I-C-FUN  

Official title:

Effects of Remote Limb Ischemic Conditioning to Enhance Muscle Power, Dynamic Balance, and Walking Performance in Children With Cerebral Palsy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04598711
• Other study ID #: 19-003232
• Status: Completed
• Phase: N/A
• Start date: June 15, 2021
• Est. completion date: December 30, 2022

Study information

• Verified date: March 2023
• Source: East Carolina University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 30, 2022
• Est. primary completion date: December 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 16 Years

Eligibility

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

Related Conditions & MeSH terms

• Cerebral Palsy

Intervention

Behavioral:
• 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.
• 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.
• 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.
• 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.
• Treadmill Training
All participants will undergo short burst interval treadmill training using self-selected and fast walking speeds.

Locations

Country	Name	City	State
United States	East Carolina University	Greenville	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
East Carolina University

Country where clinical trial is conducted

United States, 

References & Publications (21)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View 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. — View 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. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Quadriceps Electromyography	While performing the isokinetic power testing, the electromyography (EMG) data will be recorded simultaneously. The EMG data will be used to quantify the electrical amplitude of quadriceps muscle.	Pre-intervention to 1 month post-intervention follow-up
Secondary	Gait Analysis	Lower extremity walking kinematics and kinetics will be measured using 10-camera motion analysis system (Qualisys Inc., Gothenburg, Sweden). Specific kinematic variables are hip, knee, and ankle joint torques. Kinetic variables are peak hip, knee, and ankle sagittal plane joint moments.	Pre-intervention to 1 month post-intervention follow-up
Secondary	Lower limb activity	Lower extremity activity will be measured using accelerometers (Actigraphs) worn on bilateral ankles for 24 hours. Specific accelerometry variable will be number of steps.	Pre-intervention to 1 month post-intervention follow-up