Efficacy and Safety of Spinal Cord Stimulation in Patients With Spinal Cord Stimulation

Официальное название

Efficacy and Safety of Spinal Cord Stimulation in Patients With Disorders of Consciousness: A Multicenter, Double-blind, Randomized Controlled Trail

Обзор

Investigating the efficacy and safety of spinal cord stimulation for patients with disorders of consciousness.

Подробное описание

Disorder of Consciousness (DOC) is a highly significant and concerning consequence that frequently ensues various acute brain injuries. The DOC encompasses coma, unresponsive wakefulness syndrome (UWS), also known as persistent vegetative state (PVS), and minimally conscious state (MCS). Currently, the available treatments for arousing patients with DOC are relatively limited, encompassing pharmacotherapy, hyperbaric oxygen therapy, neuromodulation, physical rehabilitation exercises, and traditional Chinese acupuncture. Among these approaches, only amantadine and transcranial direct current stimulation have demonstrated efficacy in DOC patients; however, further extensive validation is still warranted.

In recent years, spinal cord stimulation (SCS) has emerged as a cutting-edge and extensively researched modality for arousal therapy. SCS is a form of neuromodulation therapy primarily utilized for intractable pain, diabetic neuropathy, and muscle spasticity, the therapeutic efficacy of the SCS is both significant and safe. Although preliminary studies have demonstrated the potential of SCS in promoting arousal in patients with DOC, these findings are currently limited to small sample reports. Therefore, this multicenter randomized controlled trial aims to provide robust evidence on the effectiveness of SCS in promoting arousal among patients with DOC, thereby standardizing its clinical application and offering advanced evidence-based medicine for DOC management.

Вмешательства

• Процедура SCS Stimulation
  Participants will accept the SCS stimulus for six months
• Процедура Sham Stimulation
  Sham stimulation will be performed in the first three months after surgery, and SCS stimulation will be started in the fourth month after surgery

Первичные конечные точки

• Effective rate of awakening [Срок оценки: SCS stimulation for 3 months after operation]

Вторичные конечные точки (9)

• The difference of CRS-R scale relative to baseline between SCS group and Sham group [Срок оценки: SCS stimulation for 14 days, 1-month-postoperative-stimulation, 3-month-postoperative-stimulation, 6-month-postoperative-stimulation]
• The difference of SECONDs scale relative to baseline between SCS group and Sham group [Срок оценки: SCS stimulation for 14 days, 1-month-postoperative-stimulation, 3-month-postoperative-stimulation, 6-month-postoperative-stimulation]
• The difference of modified Ashworth scale relative to baseline between SCS group and Sham group [Срок оценки: SCS stimulation for 14 days, 1-month-postoperative-stimulation, 3-month-postoperative-stimulation, 6-month-postoperative-stimulation]
• The NCS-R scale relative to baseline between SCS group and Sham group [Срок оценки: SCS stimulation for 14 days, 1-month-postoperative-stimulation, 3-month-postoperative-stimulation, 6-month-postoperative-stimulation]
• The difference of effective rate of awakening between SCS group and Sham group by SECONDs scale [Срок оценки: SCS stimulation for 3-month-postoperative-stimulation]
• SCS stimulation for 6-month-postoperative-stimulation, the difference of effective rate of awakening between SCS group and Sham group by CRS-R scale [Срок оценки: SCS stimulation for 6-month-postoperative-stimulation]
• The difference of effective rate of awakening between SCS group and Sham group by SECONDs scale [Срок оценки: SCS stimulation for 6-month-postoperative-stimulation]
• The difference of recovery trajectories of consciousness level between SCS group and Sham group [Срок оценки: SCS stimulation for 6-month-postoperative-stimulation]
• The difference of effective rate of awakening of 3 month s of sham stimulation and 3 month s of SCS stimulation in Sham group [Срок оценки: 6-month-postoperation]

Критерии участия

Критерии включения

• Male and female patients between the ages of 18 and 65, experiencing DOC for a duration ranging from 3 months to 1 year following brain disease.
• Patients diagnosed with DOC as a consequence of traumatic brain injury, hypertensive intracerebral hemorrhage, or severe cerebral infarction.
• Patients exhibiting stable cerebral anatomy and no need for further cranioplasty or hydrocephalus shunt.
• Patients in MCS, who fulfill at least one of the following criteria: ① Demonstrating an oriented response to noxious stimuli; ② Exhibiting sustained eye tracking behavior; ③ Displaying purposeful movements; ④ Manifesting comprehension of language or emotions and actions (often observed in specific environments such as when hearing family members crying).
• The vital signs and state of consciousness are stable: normal body temperature, the spontaneous breathing is stable (minimal sputum production and respiratory stability without oxygen supplementation for at least 2 hours); there is no significant change in the level of consciousness for at least 1 month and more.
• Presence of short-latency responses (N20/P25) on somatosensory evoked potentials (SEP) recorded from the median nerve in the upper limbs.
• Written informed consent obtained from legal guardians or representatives.

Критерии исключения

• Patients with a history of severe neurological or psychiatric disorders, or other significant diseases impacting prognosis prior to the onset of DOC;
• Patients with contraindications for surgery, such as acute infections or coagulation disorders;
• Patients who require short-wave diathermy treatment and are unable to undergo neurostimulation;
• Patients with hypoxic brain injury due to suffocation, cardiac arrest, or respiratory arrest;
• Patients with brainstem hemorrhage;
• Pregnant women;
• Patients who voluntarily request SCS implantation but are unwilling to cooperate with the research protocol;
• Participants in other clinical trials.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 3 центра

• The First Affiliated Hospital of Fujian Medical University — Фучжоу
• Xiangya Hospital,Central South University — Чанша
• Department of Neurosurgery, Huashan Hospital, Fudan University — Шанхай

Публикации

• van Erp WS, Lavrijsen JC, Vos PE, Bor H, Laureys S, Koopmans RT. The vegetative state: prevalence, misdiagnosis, and treatment limitations. J Am Med Dir Assoc. 2015 Jan;16(1):85.e9-85.e14. doi: 10.1016/j.jamda.2014.10.014. PMID 25528282
• Maas AIR, Menon DK, Manley GT, Abrams M, Akerlund C, Andelic N, Aries M, Bashford T, Bell MJ, Bodien YG, Brett BL, Buki A, Chesnut RM, Citerio G, Clark D, Clasby B, Cooper DJ, Czeiter E, Czosnyka M, Dams-O'Connor K, De Keyser V, Diaz-Arrastia R, Ercole A, van Essen TA, Falvey E, Ferguson AR, Figaji A, Fitzgerald M, Foreman B, Gantner D, Gao G, Giacino J, Gravesteijn B, Guiza F, Gupta D, Gurnell M, PMID 36183712
• Wu S, Wu B, Liu M, Chen Z, Wang W, Anderson CS, Sandercock P, Wang Y, Huang Y, Cui L, Pu C, Jia J, Zhang T, Liu X, Zhang S, Xie P, Fan D, Ji X, Wong KL, Wang L; China Stroke Study Collaboration. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol. 2019 Apr;18(4):394-405. doi: 10.1016/S1474-4422(18)30500-3. PMID 30878104
• Multi-Society Task Force on PVS. Medical aspects of the persistent vegetative state (1). N Engl J Med. 1994 May 26;330(21):1499-508. doi: 10.1056/NEJM199405263302107. PMID 7818633
• Giacino JT, Ashwal S, Childs N, Cranford R, Jennett B, Katz DI, Kelly JP, Rosenberg JH, Whyte J, Zafonte RD, Zasler ND. The minimally conscious state: definition and diagnostic criteria. Neurology. 2002 Feb 12;58(3):349-53. doi: 10.1212/wnl.58.3.349. PMID 11839831
• Thibaut A, Bruno MA, Ledoux D, Demertzi A, Laureys S. tDCS in patients with disorders of consciousness: sham-controlled randomized double-blind study. Neurology. 2014 Apr 1;82(13):1112-8. doi: 10.1212/WNL.0000000000000260. Epub 2014 Feb 26. PMID 24574549
• Giacino JT, Whyte J, Bagiella E, Kalmar K, Childs N, Khademi A, Eifert B, Long D, Katz DI, Cho S, Yablon SA, Luther M, Hammond FM, Nordenbo A, Novak P, Mercer W, Maurer-Karattup P, Sherer M. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med. 2012 Mar 1;366(9):819-26. doi: 10.1056/NEJMoa1102609. PMID 22375973
• Denison T, Morrell MJ. Neuromodulation in 2035: The Neurology Future Forecasting Series. Neurology. 2022 Jan 11;98(2):65-72. doi: 10.1212/WNL.0000000000013061. PMID 35263267

Идентификаторы

NCT: NCT06515132 · KY2024-752

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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