Effect of NMES on Spasticity

Официальное название

The Effect of Neuromuscular Electrical Stimulation on Spasticity: A Single-Subject Experimental Study

Обзор

The goal of this clinical trial is to learn if neuromuscular electrical stimulation (NMES) works to treat spasticity in adult patients with spasticity related to stroke. The main question it aims to answer is: • Does NMES reduces the severity of spasticity? Researchers will compare NMES treatment to baseline and non-stimulation periods to see if NMES works to treat spasticity. Participants will: • first undergo an initial assessment at 10-minute intervals for one hour, followed by 20 minutes of NMES exposure, and subsequent post-treatment assessments at 10-minute intervals for two hours. This daily procedure will be repeated over four days for one patient, and performed only once for the remaining three patients.

Подробное описание

Spasticity is a sensory-motor control disorder arising from upper motor neuron lesions, affecting approximately 97% of chronic stroke patients presenting with moderate-to-severe motor impairment. This pathology is driven by stretch reflex hyperexcitability, stemming from secondary alterations in the supraspinal, spinal interneuronal, and striated muscle systems; it manifests as an exaggerated reflex response to peripheral stimuli and concomitant excessive muscle activity. While several definitions exist in the literature, the operational conceptualization of spasticity as 'the enhancement of velocity-dependent stretch reflexes, measured at rest' establishes it as a highly quantifiable and robust target variable for clinical evaluation and scientific investigation.

Spasticity management encompasses diverse therapeutic modalities, ranging from pharmacological to non-pharmacological approaches. Among these, neuromuscular electrical stimulation (NMES) has emerged as a prominent intervention. Although documented as a beneficial adjunctive therapy, the clinical translation of NMES from randomized controlled trials to bedside practice is frequently hindered by marked study heterogeneity and a scarcity of high-quality evidence. Moreover, despite its clinical adoption, NMES application parameters remain largely unstandardized, and substantial inter-individual variability precludes the direct extrapolation of group-level averages to individual patients. Therefore, rigorous experimental frameworks capable of generating robust, individual-level scientific evidence are required to guide real-world practice and optimize personalized therapeutic decisions. Within this paradigm, single-subject experimental designs represent a highly promising methodological approach.

Consequently, this study investigates the therapeutic efficacy of NMES on spasticity among chronic stroke patients with spastic paresis lasting longer than one year, utilizing single-subject experimental methodologies-specifically withdrawal/reversal and multiple-baseline designs. To achieve this, this research addresses four primary objectives: evaluating whether standalone NMES reduces spasticity severity; determining the longevity of any observed therapeutic effect; quantifying the precise magnitude of this intervention; and examining the generalizability of the outcomes. Framed within the context of the experimental design-analysis paradigm, we hypothesize that isolated NMES application will significantly reduce spasticity. This hypothesis will be systematically tested across three distinct stages. The initial pilot stage will delineate the presence, magnitude, and duration of NMES efficacy using predefined stimulation parameters. Subsequently, the second stage will implement a withdrawal/reversal design with built-in wash-out periods to provide robust causal evidence regarding NMES outcomes. Finally, the third stage will deploy a multiple-baseline design across participants to establish the generalizability of the intervention parameters.

In the first stage, a basic phase-change (A-B) design will be applied to a single participant, where Phase A represents the untreated baseline period, and Phase B denotes the NMES application followed immediately by post-treatment assessments. Specifically, the participant will undergo a baseline assessment at 10-minute intervals for one hour, followed by a 20-minute NMES application, and subsequent post-treatment assessments at 10-minute intervals for two hours. This initial stage serves as a pilot phase designed to evaluate potential NMES-related effects, and progression to Stage 2 will occur independently of the treatment's efficacy status during this pilot.

In the second stage, this daily procedure is planned to be repeated over four consecutive days separated by washout intervals for the same participant, yielding a full A-B-A-B-A-B-A sequence. However, the study incorporates a strict ethical stopping rule: if visual analysis reveals no positive clinical response by the end of the second day (concluding the initial A-B-A-B phases), the protocol will be discontinued immediately due to futility, and the study will not proceed to the final stage. Conversely, if a positive response is verified visually, the full four-day sequence will be completed, and a non-concurrent multiple baseline design across participants (the final stage) will subsequently be implemented.

In the final stage, the single-day (A-B) procedure will be applied only once to three additional participants. To ensure methodological rigor, the baseline lengths for these three participants will consist of 5, 7, and 9 assessments, respectively, assigned in a randomized order.

Вмешательства

• Устройство Neuromuscular electrical stimulation (NMES)
  Neuromuscular electrical stimulation (NMES) (a symmetric, biphasic, rectangular waveform) will be administered to the antagonist wrist extensors (extensor carpi radialis longus/brevis and extensor carpi ulnaris) of the spastic wrist flexors in the B phase. The configuration consists of an application duration of 20 minutes, a stimulation frequency of 35 Hz, and a pulse duration of 300 μs. The duty cycle will feature a 20-second ON time and 20-second OFF time (1:1 ratio), with ramp-up and ramp-do
• Устройство Neuromuscular electrical stimulation (NMES)
  Neuromuscular electrical stimulation (NMES) is a therapeutic modality used in neurorehabilitation. By delivering transcutaneous electrical currents, NMES elicits repetitive, patterned muscle contractions to augment or restore motor functions.

Первичные конечные точки

• Angle of Muscle Reaction [Срок оценки: From enrollment up to 1 day (Stages 1 and 3) or 2 to 4 days (Stage 2), depending on the assigned stage.]
• Hmax / Mmax ratio [Срок оценки: From enrollment to the completion of treatment, varying by stage: 1 day for Stages 1 and 3, and 2 to 4 days for Stage 2.]

Критерии участия

Критерии включения

• Age between 18 and 70 years
• Post-stroke wrist flexor spasticity scored as Grade 2 or 3 on the Australian Spasticity Assessment Scale (ASAS), specifically selecting patients whose passive stretch resistance (post-catch response) can be easily overcome to ensure accurate and unconfounded electrophysiological evaluation.
• Provision of voluntary, written informed consent prior to study enrollment.

Критерии исключения

• Age <18 or >70 year
• Contraindications to neuromuscular electrical stimulation (e.g., active electronic implants, history of epilepsy, or localized skin lesions preventing electrode placement)
• Concomitant wrist contracture or pain sufficient to impede clinical evaluation
• Structural abnormalities of the elbow joint obstructing median nerve stimulation
• Median nerve neuropathy or injury in the ipsilateral upper extremity.
• Non-stable dosage of antispastic medications within the 2 weeks prior to baseline
• Initiation of medications affecting nerve conduction (e.g., antidepressants, anticonvulsants, anesthetics) within the past month; patients on a stable dose for >1 month remain eligible
• Botulinum toxin infiltration in the target spastic muscles within the preceding 3 months
• History of neurolytic procedures targeting spasticity in the affected limb.
• History of orthopedic or neurological surgery targeting spasticity in the affected limb
• Cognitive impairment severe enough to compromise adherence to study protocols
• Inability to maintain the required testing positions for the upper extremity joints (shoulder, elbow, forearm, and wrist)
• Pregnancy

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Turkey (Türkiye) · 1 центр

• İzmir Katip Çelebi University — Izmir

Публикации

• Love S, Gibson N, Smith N, Bear N, Blair E; Australian Cerebral Palsy Register Group. Interobserver reliability of the Australian Spasticity Assessment Scale (ASAS). Dev Med Child Neurol. 2016 Feb;58 Suppl 2:18-24. doi: 10.1111/dmcn.13000. Epub 2016 Jan 14. PMID 26762706
• Childers MK, Biswas SS, Petroski G, Merveille O. Inhibitory casting decreases a vibratory inhibition index of the H-reflex in the spastic upper limb. Arch Phys Med Rehabil. 1999 Jun;80(6):714-6. doi: 10.1016/s0003-9993(99)90178-8. PMID 10378501
• Katz RT, Rovai GP, Brait C, Rymer WZ. Objective quantification of spastic hypertonia: correlation with clinical findings. Arch Phys Med Rehabil. 1992 Apr;73(4):339-47. doi: 10.1016/0003-9993(92)90007-j. PMID 1554307
• He J, Luo A, Yu J, Qian C, Liu D, Hou M, Ma Y. Quantitative assessment of spasticity: a narrative review of novel approaches and technologies. Front Neurol. 2023 Jul 5;14:1121323. doi: 10.3389/fneur.2023.1121323. eCollection 2023. PMID 37475737
• Burke D. Clinical uses of H reflexes of upper and lower limb muscles. Clin Neurophysiol Pract. 2016 Apr 7;1:9-17. doi: 10.1016/j.cnp.2016.02.003. eCollection 2016. PMID 30214954
• Cameron T, McDonald K, Anderson L, Prochazka A. The effect of wrist angle on electrically evoked hand opening in patients with spastic hemiplegia. IEEE Trans Rehabil Eng. 1999 Mar;7(1):109-11. doi: 10.1109/86.750560. PMID 10188613
• Sentandreu-Mano T, Tomas JM, Ricardo Salom Terradez J. A randomised clinical trial comparing 35 Hz versus 50 Hz frequency stimulation effects on hand motor recovery in older adults after stroke. Sci Rep. 2021 Apr 28;11(1):9131. doi: 10.1038/s41598-021-88607-8. PMID 33911100
• Malhotra S, Rosewilliam S, Hermens H, Roffe C, Jones P, Pandyan AD. A randomized controlled trial of surface neuromuscular electrical stimulation applied early after acute stroke: effects on wrist pain, spasticity and contractures. Clin Rehabil. 2013 Jul;27(7):579-90. doi: 10.1177/0269215512464502. Epub 2012 Nov 5. PMID 23129814

Идентификаторы

NCT: NCT07617311 · 2026-KAE-0011

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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