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With the rapid development of life support technology, more and more people can survive severe brain injury. Some survivors regain consciousness after a period of coma, however, many patients develop prolonged disorders of consciousness (DOC), which poses a therapeutic challenge for clinicians and a heavy burden for their families. The investigators design an Electro-acupuncture to treat disorder of consciousness (AcuDoc) trial with the aim of validating the clinical effect of electroacupuncture in treating DOC and exploring its therapeutic mechanisms by integrating EEG, neuroimaging, evoked potential tests, and behavioral assessments.
The AcuDoc trial is a single-center, prospective, triple masking, randomized, sham electroacupuncture-controlled study. A total of 50 adult patients with DOC and 25 healthy subjects will be enrolled in the study . Patients will be randomized into electroacupuncture (EA) group or sham EA group (1:1). All patients will receive EA or sham-EA treatment in the supine position at 9 am for 30 minutes once a day for consecutive 14 days and healthy subjects will receive no treatments. The primary objective is to determine the therapeutic benefit of electroacupuncture on the recovery of consciousness in patients with DOC after a 2-week intervention. Key secondary objective is to investigate the effect of electroacupuncture on the circuitry of consciousness using a multimodal approach integrating EEG, neuroimaging (rs-fMRI, amide proton transfer imaging, intravoxel incoherent motion imaging, neurite orientation dispersion and density imaging), and evoked potentials (SEP, BAEP). Other secondary outcomes include the effect of EA on the assessment of brain-computer interface after a 2-week intervention and on the Glasgow Outcome Scale-Extended score at 30 days and 90 days .
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Electro-acupuncture group | Experimental | Patients in EA group receive acupuncture at Shuigou (also known as Renzhong, GV26) and Yintang (updated number GV24+, previous number GV29). Paired electrodes from the EA apparatus are clipped to the needle handles at Shuigou and Yintang. The electroacupuncture stimulation lasts for 30 minutes with a wave of rarefaction and condensation (10 Hz / 50 Hz) and a current intensity of the maximum withstand current within 7mA. All patients receive EA at 9 am for 30 minutes once a day for consecutive 14 days. |
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| Sham electro-acupuncture group | Sham Comparator | Patients in sham-EA group receive sham-EA at sham-Shuigou and sham-Yintang.Acupuncture needles are inserted into the adhesive pads but do not pierce the skin. Paired electrodes from the EA apparatus via sham connecting cords are clipped to the needle handles at sham-Shuigou and sham-Yintang. The sham connecting cords are similar in appearance to the normal ones, but the inner wires in sham connecting cords are cut off and cannot conduct electricity. All patients receive sham-EA at 9 am for 30 minutes once a day for consecutive 14 days. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Electroacupuncture | Other | Electro-acupuncture at Shuigou and Yintang. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Coma Recovery Scale - Revised score | 0 - 23, a higher score indicates a better level of consciousness | after 14 days of EA or sham-EA treatment |
| Measure | Description | Time Frame |
|---|---|---|
| phase locking value | measured by electroencephalogram | after 14 days of EA or sham-EA treatment |
| amplitude of low-frequency fluctuation | measured by resting-state functional magnetic resonance imaging |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Fang Yuan, PhD | Contact | +86-20-81887233 | yuanfang@gzucm.edu.cn | |
| Jixiang Chen, PhD | Contact | 756337176@qq.com |
| Name | Affiliation | Role |
|---|---|---|
| Fang Yuan, PhD | The Second Affiliated Hospital of Guangzhou University of Chinese Medicine | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Second Affiliated Hospital of Guangzhou University of Chinese Medicine | Recruiting | Guangzhou | Guangdong | 510120 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31003899 | Background | 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. | |
| 21040571 | Background | Laureys S, Celesia GG, Cohadon F, Lavrijsen J, Leon-Carrion J, Sannita WG, Sazbon L, Schmutzhard E, von Wild KR, Zeman A, Dolce G; European Task Force on Disorders of Consciousness. Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome. BMC Med. 2010 Nov 1;8:68. doi: 10.1186/1741-7015-8-68. |
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The detailed datasets used and/or analyzed during the current study are available upon reasonable request.
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| ID | Term |
|---|---|
| D003244 | Consciousness Disorders |
| D001930 | Brain Injuries |
| ID | Term |
|---|---|
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D015671 | Electroacupuncture |
| ID | Term |
|---|---|
| D003131 | Combined Modality Therapy |
| D013812 | Therapeutics |
| D015670 | Acupuncture Therapy |
| D000529 | Complementary Therapies |
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| Sham electroacupuncture |
| Other |
Sham-EA at sham-Shuigou and sham-Yintang. |
|
| after 14 days of EA or sham-EA treatment |
| Amide proton transfer-weighted signal | measured by amide proton transfer imaging | after 14 days of EA or sham-EA treatment |
| f value | measured by intravoxel incoherent motion imaging | after 14 days of EA or sham-EA treatment |
| neurite density index | measured by neurite orientation dispersion and density imaging | after 14 days of EA or sham-EA treatment |
| latency value of N20 | measured by somatosensory evoked potential biomarkers | after 14 days of EA or sham-EA treatment |
| latency between III and V potentials | measured by brainstem auditory evoked potential | after 14 days of EA or sham-EA treatment |
| Glasgow Outcome Scale-Extended score | 1 - 8, a higher score indicates better functional recovery from brain injury | 30 days after randomization |
| Glasgow Outcome Scale-Extended score | 1 - 8, a higher score indicates better functional recovery from brain injury | 90 days after randomization |
| brain-computer interface accuracy | measured by electroencephalogram-based brain-computer interface experiment | after 14 days of EA or sham-EA treatment |
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| 21674197 | Background | Bruno MA, Vanhaudenhuyse A, Thibaut A, Moonen G, Laureys S. From unresponsive wakefulness to minimally conscious PLUS and functional locked-in syndromes: recent advances in our understanding of disorders of consciousness. J Neurol. 2011 Jul;258(7):1373-84. doi: 10.1007/s00415-011-6114-x. Epub 2011 Jun 16. |
| 8340806 | Background | Steriade M, Nunez A, Amzica F. A novel slow (< 1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components. J Neurosci. 1993 Aug;13(8):3252-65. doi: 10.1523/JNEUROSCI.13-08-03252.1993. |
| 11073868 | Background | Timofeev I, Grenier F, Bazhenov M, Sejnowski TJ, Steriade M. Origin of slow cortical oscillations in deafferented cortical slabs. Cereb Cortex. 2000 Dec;10(12):1185-99. doi: 10.1093/cercor/10.12.1185. |
| 19954851 | Background | Schiff ND. Recovery of consciousness after brain injury: a mesocircuit hypothesis. Trends Neurosci. 2010 Jan;33(1):1-9. doi: 10.1016/j.tins.2009.11.002. Epub 2009 Dec 1. |
| 30089617 | Background | 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. Comprehensive systematic review update 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):461-470. doi: 10.1212/WNL.0000000000005928. Epub 2018 Aug 8. |
| 36875660 | Background | Li H, Zhang X, Sun X, Dong L, Lu H, Yue S, Zhang H. Functional networks in prolonged disorders of consciousness. Front Neurosci. 2023 Feb 17;17:1113695. doi: 10.3389/fnins.2023.1113695. eCollection 2023. |
| 33318675 | Background | Edlow BL, Claassen J, Schiff ND, Greer DM. Recovery from disorders of consciousness: mechanisms, prognosis and emerging therapies. Nat Rev Neurol. 2021 Mar;17(3):135-156. doi: 10.1038/s41582-020-00428-x. Epub 2020 Dec 14. |
| 16014785 | Background | Rudolph M, Pelletier JG, Pare D, Destexhe A. Characterization of synaptic conductances and integrative properties during electrically induced EEG-activated states in neocortical neurons in vivo. J Neurophysiol. 2005 Oct;94(4):2805-21. doi: 10.1152/jn.01313.2004. Epub 2005 Jul 13. |
| 23747956 | Background | Howell K, Grill E, Klein AM, Straube A, Bender A. Rehabilitation outcome of anoxic-ischaemic encephalopathy survivors with prolonged disorders of consciousness. Resuscitation. 2013 Oct;84(10):1409-15. doi: 10.1016/j.resuscitation.2013.05.015. Epub 2013 Jun 6. |
| 33488494 | Background | Perez P, Valente M, Hermann B, Sitt J, Faugeras F, Demeret S, Rohaut B, Naccache L. Auditory Event-Related "Global Effect" Predicts Recovery of Overt Consciousness. Front Neurol. 2021 Jan 8;11:588233. doi: 10.3389/fneur.2020.588233. eCollection 2020. |
| 29871771 | Background | Threlkeld ZD, Bodien YG, Rosenthal ES, Giacino JT, Nieto-Castanon A, Wu O, Whitfield-Gabrieli S, Edlow BL. Functional networks reemerge during recovery of consciousness after acute severe traumatic brain injury. Cortex. 2018 Sep;106:299-308. doi: 10.1016/j.cortex.2018.05.004. Epub 2018 May 12. |
| 30775433 | Background | Demertzi A, Tagliazucchi E, Dehaene S, Deco G, Barttfeld P, Raimondo F, Martial C, Fernandez-Espejo D, Rohaut B, Voss HU, Schiff ND, Owen AM, Laureys S, Naccache L, Sitt JD. Human consciousness is supported by dynamic complex patterns of brain signal coordination. Sci Adv. 2019 Feb 6;5(2):eaat7603. doi: 10.1126/sciadv.aat7603. eCollection 2019 Feb. |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
| D004599 |
| Electric Stimulation Therapy |
| D026741 | Physical Therapy Modalities |
| D012046 | Rehabilitation |
| D004561 | Transcutaneous Electric Nerve Stimulation |
| D000698 | Analgesia |
| D000760 | Anesthesia and Analgesia |
| D000758 | Anesthesia |