Efficacy and Safety of Spinal Cord Stimulation in Patients With Spinal Cord Stimulation (SCORS-DOC)

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

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

Study Overview

• Status: Recruiting
• Conditions: Disorder of Consciousness; Spinal Cord Stimulation
• Intervention / Treatment: Procedure: SCS Stimulation; Procedure: Sham Stimulation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xuehai Wu, Ph.D.; Phone Number: +8613764880571; Email: Wuxuehai2013@163.com
• Study Contact Backup: Name: Lijian Lang, M.M.; Phone Number: +8613896851367; Email: lang_lijian@163.com

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Recruiting
      • The First Affiliated Hospital of Fujian Medical University
      • Contact: Peisen Yao, Ph.D.; Phone Number: 18650084102
  • Hunan
    • Changsha, Hunan, China, 410000
      • Recruiting
      • Xiangya hospital，Central South University
      • Contact: Zhongyi Sun, Ph.D.; Phone Number: 18163618671
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Department of Neurosurgery, Huashan Hospital, Fudan University
      • Contact: Xuehai Wu, Ph.D.; Phone Number: +8613764880571; Email: Wuxuehai2013@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SCS group; SCS stimulation therapy is initiated 1 week post-surgery, which is administered continuously for a duration of 6 months.	Procedure: SCS Stimulation; Participants will accept the SCS stimulus for six months
Sham Comparator: Sham group; Sham stimulation therapy is initiated 1 week post-surgery, and SCS stimulation therapy is initiated 3 months post-surgery, which is stimulated continuously for a duration of 3 months.	Procedure: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effective rate of awakening	The CRS-R is employed, with a minimum of 5 CRS-R assessments conducted at each follow-up time point, accompanied by simultaneous video recording. And the highest value is scored as a state of consciousness. The clinical assessment of participants' consciousness is deemed significantly improved when it fulfills the following criteria: a) MCS- recover to consciousness level of MCS+ or higher; b) MCS status (MCS- or MCS+) recover to emergence from MCS (restoration of functional communication).	SCS stimulation for 3 months after operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference of CRS-R scale relative to baseline between SCS group and Sham group	The Coma Recovery Scale-Revised (CRS-R) is a standardized neurobehavioral assessment measure designed for use in patients with disorders of consciousness. It has good validity, reliability and practicability.	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	The Simplified Evaluation of CONsciousness Disorders (SECONDs) is a fast tool to assess consciousness in brain-injured patients.	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	The modified Ashworth scale is the most universally accepted clinical tool used to measure the increase of muscle tone.	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	The Nociception Coma Scale-Revised (NCS-R) was developed to help assess pain in patients with disorders of consciousness (DOC). Several studies have shown its sensitivity in assessing response to acute noxious stimuli.	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		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		SCS stimulation for 6-month-postoperative-stimulation
The difference of effective rate of awakening between SCS group and Sham group by SECONDs scale		SCS stimulation for 6-month-postoperative-stimulation
The difference of recovery trajectories of consciousness level between SCS group and Sham group		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		6-month-postoperation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Security outcome	Incidence of postoperative infections within 3 months after operation	3 months after operation
Security outcome	Incidence of postoperative hemorrhage within 3 months after operation	3 months after operation

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Collaborators: Xiangya Hospital of Central South University; First Affiliated Hospital of Fujian Medical University
• Investigators: Principal Investigator: Xuehai Wu, Ph.D., Department of Neurosurgery, Huashan Hospital, Fudan University

Publications and helpful links

General Publications

• 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.
• 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.
• North RB, Kidd DH, Zahurak M, James CS, Long DM. Spinal cord stimulation for chronic, intractable pain: experience over two decades. Neurosurgery. 1993 Mar;32(3):384-94; discussion 394-5. doi: 10.1227/00006123-199303000-00008.
• Mekhail N, Levy RM, Deer TR, Kapural L, Li S, Amirdelfan K, Hunter CW, Rosen SM, Costandi SJ, Falowski SM, Burgher AH, Pope JE, Gilmore CA, Qureshi FA, Staats PS, Scowcroft J, Carlson J, Kim CK, Yang MI, Stauss T, Poree L; Evoke Study Group. Long-term safety and efficacy of closed-loop spinal cord stimulation to treat chronic back and leg pain (Evoke): a double-blind, randomised, controlled trial. Lancet Neurol. 2020 Feb;19(2):123-134. doi: 10.1016/S1474-4422(19)30414-4. Epub 2019 Dec 20.
• 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.
• 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.
• 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.
• Thibaut A, Schiff N, Giacino J, Laureys S, Gosseries O. Therapeutic interventions in patients with prolonged disorders of consciousness. Lancet Neurol. 2019 Jun;18(6):600-614. doi: 10.1016/S1474-4422(19)30031-6. Epub 2019 Apr 16.
• Petersen EA, Stauss TG, Scowcroft JA, Brooks ES, White JL, Sills SM, Amirdelfan K, Guirguis MN, Xu J, Yu C, Nairizi A, Patterson DG, Tsoulfas KC, Creamer MJ, Galan V, Bundschu RH, Paul CA, Mehta ND, Choi H, Sayed D, Lad SP, DiBenedetto DJ, Sethi KA, Goree JH, Bennett MT, Harrison NJ, Israel AF, Chang P, Wu PW, Gekht G, Argoff CE, Nasr CE, Taylor RS, Subbaroyan J, Gliner BE, Caraway DL, Mekhail NA. Effect of High-frequency (10-kHz) Spinal Cord Stimulation in Patients With Painful Diabetic Neuropathy: A Randomized Clinical Trial. JAMA Neurol. 2021 Jun 1;78(6):687-698. doi: 10.1001/jamaneurol.2021.0538.
• 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. Erratum In: J Am Med Dir Assoc. 2019 May;20(5):652. doi: 10.1016/j.jamda.2019.01.145.
• 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, Haagsma JA, Hammond FM, Hawryluk G, Hutchinson P, van der Jagt M, Jain S, Jain S, Jiang JY, Kent H, Kolias A, Kompanje EJO, Lecky F, Lingsma HF, Maegele M, Majdan M, Markowitz A, McCrea M, Meyfroidt G, Mikolic A, Mondello S, Mukherjee P, Nelson D, Nelson LD, Newcombe V, Okonkwo D, Oresic M, Peul W, Pisica D, Polinder S, Ponsford J, Puybasset L, Raj R, Robba C, Roe C, Rosand J, Schueler P, Sharp DJ, Smielewski P, Stein MB, von Steinbuchel N, Stewart W, Steyerberg EW, Stocchetti N, Temkin N, Tenovuo O, Theadom A, Thomas I, Espin AT, Turgeon AF, Unterberg A, Van Praag D, van Veen E, Verheyden J, Vyvere TV, Wang KKW, Wiegers EJA, Williams WH, Wilson L, Wisniewski SR, Younsi A, Yue JK, Yuh EL, Zeiler FA, Zeldovich M, Zemek R; InTBIR Participants and Investigators. Traumatic brain injury: progress and challenges in prevention, clinical care, and research. Lancet Neurol. 2022 Nov;21(11):1004-1060. doi: 10.1016/S1474-4422(22)00309-X. Epub 2022 Sep 29. Erratum In: Lancet Neurol. 2022 Dec;21(12):e10. doi: 10.1016/S1474-4422(22)00411-2.
• 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.
• Hara S, Andresen H, Solheim O, Carlsen SM, Sundstrom T, Lonne G, Lonne VV, Taraldsen K, Tronvik EA, Oie LR, Gulati AM, Sagberg LM, Jakola AS, Solberg TK, Nygaard OP, Salvesen OO, Gulati S. Effect of Spinal Cord Burst Stimulation vs Placebo Stimulation on Disability in Patients With Chronic Radicular Pain After Lumbar Spine Surgery: A Randomized Clinical Trial. JAMA. 2022 Oct 18;328(15):1506-1514. doi: 10.1001/jama.2022.18231.
• Funahashi K, Komai N, Ogura M, Kuwata T, Nakai M, Tsuji N. [Effects and indications of spinal cord stimulation on the vegetative syndrome]. No Shinkei Geka. 1989 Oct;17(10):917-23. Japanese.
• Kanno T, Morita I, Yamaguchi S, Yokoyama T, Kamei Y, Anil SM, Karagiozov KL. Dorsal column stimulation in persistent vegetative state. Neuromodulation. 2009 Jan;12(1):33-8. doi: 10.1111/j.1525-1403.2009.00185.x.
• Piedade GS, Assumpcao de Monaco B, Guest JD, Cordeiro JG. Review of spinal cord stimulation for disorders of consciousness. Curr Opin Neurol. 2023 Dec 1;36(6):507-515. doi: 10.1097/WCO.0000000000001222. Epub 2023 Oct 26.
• Kinfe TM, Pintea B, Vatter H. Is Spinal Cord Stimulation Useful and Safe for the Treatment of Chronic Pain of Ischemic Origin? A Review. Clin J Pain. 2016 Jan;32(1):7-13. doi: 10.1097/AJP.0000000000000229.
• Giacino JT, Katz DI, Schiff ND, Whyte J, Ashman EJ, Ashwal S, Barbano R, Hammond FM, Laureys S, Ling GSF, Nakase-Richardson R, Seel RT, Yablon S, Getchius TSD, Gronseth GS, Armstrong MJ. Practice guideline update recommendations summary: Disorders of consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research. Neurology. 2018 Sep 4;91(10):450-460. doi: 10.1212/WNL.0000000000005926. Epub 2018 Aug 8. Erratum In: Neurology. 2019 Jul 16;93(3):135. doi: 10.1212/WNL.0000000000007382.

Study record dates

Study Major Dates

• Study Start (Estimated): January 10, 2025
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): May 30, 2026

Study Registration Dates

• First Submitted: June 23, 2024
• First Submitted That Met QC Criteria: July 18, 2024
• First Posted (Actual): July 23, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 4, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Spinal Cord Stimulation; Disorder of Consciousness; Randomized clinical trail
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Neurobehavioral Manifestations; Neurocognitive Disorders; Consciousness Disorders
• Other Study ID Numbers: KY2024-752

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No