Clinical trial NCT06860464: Remote Ischemic Conditioning and Spinal Reflex Modulation
Official title: Effects of Remote Ischemic Conditioning Combined with Motor Training on Spinal Reflex Modulation in Healthy Young Adults
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Healthy Young Adults
Keywords: Remote ischemic conditioning
Spinal reflex modulation
H-reflex
Balance training
Lead sponsor: East Carolina University
Sponsor class: OTHER
First posted: 2025-03-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Remote ischemic conditioning (RIC) is a clinically feasible method that protects distant organs from severe injury through brief, sub lethal periods of ischemia followed by re-perfusion. Recent studies suggest that RIC, combined with training, improves muscle strength and balance in healthy adults and post-stroke survivors. While the underlying mechanisms are not fully understood, RIC's neuroprotective effects - such as promoting angiogenesis, neurogenesis, and modulating glutamate and GABA synthesis - overlap with neuroplasticity processes. Evidence indicates that neuroplasticity from exercise training occurs not only in the cerebral cortex but also within the spinal cord, yet the role of spinal reflex mechanisms underlying the benefits of RIC remains under explored. Therefore, this study aims to investigate effects of RIC on spinal reflex modulation in healthy adults, both independently and combined with balance training.

Detailed description: Ischemic conditioning (IC) is an endogenous phenomenon that protects target organs from severe ischemic events by applying alternating cycles of brief, sublethal ischemia followed by reperfusion. Remote ischemic conditioning (RIC) is a more feasible, non-invasive method of delivering IC. It involves using a standard blood pressure cuff on either the arm or leg to induce brief periods of sublethal ischemia. Extensive evidence from both animal and human studies indicates that RIC provides neuroprotection through multifactorial mechanisms involving inflammatory, oxidative, excitotoxic, metabolic, vascular, and glial pathways. Additionally, several studies demonstrate the involvement of peripheral somatosensory, spinal cord, and autonomic pathways in RIC-induced neuroprotection. Prior research also shows that RIC enhances motor learning (balance performance) when paired with motor training in both young and older adults. While a wealth of research has shown that neuroplasticity in response to training occurs in cortical and spinal neural circuits, limited studies have explored the effects of RIC on spinal modulations in healthy adults. Notably, only one study has reported a reduction in Hoffman (H)-reflex amplitudes with RIC. Given the evidence of peripheral neuronal pathways involved in RIC and its positive impact on balance performance, it is plausible that RIC could lead to spinal reflex modulations and enhance balance improvements in healthy adults. These modulations may be further amplified when RIC is combined with balance training. The specific aims of this study are: 1) to investigate whether RIC modulates spinal reflex mechanisms, as reflected by the H-reflex, 2) to explore whether combining RIC with motor training has additive effects on spinal reflex modulations, and 3) to compare the differences in spinal reflex modulation between single and multiple (five) sessions of RIC + motor training in healthy adults. In this single-blind, randomized controlled trial, 30 healthy adults aged 18-40 will undergo H-reflex testing on the dominant lower extremity (LE) and balance assessments. Participants will then undergo RIC or sham conditioning combined with balance training. RIC or sham conditioning will be delivered via cyclic inflation and deflation of a pressure cuff on the thigh of the dominant LE using a standard protocol. The balance training (5 days) will involve standing on a stability platform with the goal of maintaining the platform within a 5-degree horizontal range for 30 seconds across 15 trials/day. Participants will be tested at baseline, immediately post-conditioning (RIC/sham), post one session of conditioning (RIC/sham) + balance training, and after five sessions of conditioning (RIC/sham) + balance training. Investigators hypothesize that compared to sham conditioning + training, RIC + training will significantly modulate (decrease) H-reflex outcomes (Hmax, maximal H-reflex amplitude, and Hmax/Mmax ratio) and enhance balance performance in healthy adults. Furthermore, compared to multiple (five) sessions of sham conditioning combined with training, multiple sessions of RIC + training are expected to result in more significant modulations of the H-reflex and greater balance improvements.This study will help clarify whether RIC induces alterations in spinal reflex modulations when applied independently or in combination with motor training, thereby reflecting neuroplasticity within the spinal cord in healthy young adults. These findings would deepen our understanding of the spinal mechanisms underlying the benefits of RIC and could accelerate its translation for individuals with neurological disorders

Eligibility criteria: Inclusion Criteria:

* Healthy adults 18-40 years of age

Exclusion Criteria:

* Individuals with cognitive deficits or communication problems
* Individuals with impaired vision
* Individuals with balance disorders such as vestibular disorders, etc.
* Individuals who are pregnant
* Individuals with known cardiorespiratory dysfunctions
* Presence of lower extremity condition, injury, or surgery within last three months which could compromise training

Primary outcomes:
measure: Change in maximal H-reflex amplitude (Hmax)
timeFrame: Baseline, Day 2, Day 7
measure: Change in Hmax/ Mmax Ratio
timeFrame: Baseline, Day 2, Day 7
Secondary outcomes:
measure: Change in Balance Performance
timeFrame: Baseline, Day 2, Day 7
Other outcomes:
Locations:
city: Greenville
country: United States
facility: Swati Surkar
state: North Carolina
Study officials:
affiliation: East Carolina University
name: Swati M Surkar, PT, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Taube W, Kullmann N, Leukel C, Kurz O, Amtage F, Gollhofer A. Differential reflex adaptations following sensorimotor and strength training in young elite athletes. Int J Sports Med. 2007 Dec;28(12):999-1005. doi: 10.1055/s-2007-964996. Epub 2007 May 11.
citation: Quadrado IC, Cancio RB, Silva BM, Vianna LC, Mezzarane RA. Modulation of spinal cord excitability following remote limb ischemic preconditioning in healthy young men. Exp Brain Res. 2020 May;238(5):1265-1276. doi: 10.1007/s00221-020-05807-w. Epub 2020 Apr 17.
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.
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.
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.