Disorders of Consciousness Due to Severe Brain Injury
Conditions
Keywords
Transcutaneous Electrical Acupoint Stimulation, Hand Jing-Well Points, Disorders of Consciousness
Brief summary
Effective treatment options for disorders of consciousness (DoC) remain limited, and available interventions show heterogeneous efficacy. To date, limited evidences support the use of amantadine and transcranial direct current stimulation in this population. Bloodletting puncture (BP) at the hand twelve Jing-Well points (HTWPs) has been traditionally used in China as an empirical therapy for DoC; however, its efficacy has not been established by robust clinical evidence. Transcutaneous electrical acupoint stimulation (TEAS) provides a modern, noninvasive alternative for acupoint stimulation. The Wells-DoC trial, a multicenter, randomized, controlled, open-label study with blinded endpoint assessment, provided preliminary evidence that TEAS applied at the hand twelve Jing-Well points was associated with a numerically higher proportion of consciousness improvement in patients with DoC, although the difference did not reach statistical significance. These findings support the need for further evaluation in an adequately powered randomized controlled trial. The Wells-DoC II trial is a multicenter, randomized, controlled, double-blind clinical trial designed to evaluate the efficacy and safety of TEAS at the twelve Jing-Well points of the hand in patients with DoC. The primary objective of the Wells-DoC II trial is to determine whether TEAS applied at the twelve Jing-Well points of the hand improves consciousness in adults with DoC. The primary endpoint is the proportion of patients achieving consciousness improvement after 14 consecutive days of treatment, compared between the TEAS group and the sham stimulation (placebo control) group. The secondary objectives are to assess the effects of TEAS versus sham stimulation on: (1) changes in Coma Recovery Scale-Revised (CRS-R) scores at 7 and 14 days; (2) change in ABCD model classification at day 14; and (3) functional outcomes measured by the Glasgow Outcome Scale-Extended (GOSE) at 3 and 6 months after enrollment. A total of 160 patients will be recruited over a 28-month period.
Interventions
DEVICETranscutaneous electrical stimulation
Transcutaneous electrical acupoint stimulation at hand twelve jing-well points
Sham electrical acupoint stimulation at hand twelve jing-well points
Sponsors
Xijing Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All study members are blinded to randomization except the following: electrical stimulation operators in each investigation site. Electrical stimulation operators are independent of all other components of the trial and are responsible for participant randomization as well as the administration of both active TEAS and sham interventions. Consequently, they are aware of treatment allocation. To minimize bias, they will not be involved in outcome assessment, data collection beyond the intervention procedures, or statistical analysis, and will be required to maintain strict confidentiality regarding group assignments throughout the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age: 18-80 years old; * From 7 to 90 days since brain injury; * Diagnosed in VS/UWS or MCS as defined by at least two CRS-R assessments performed during the screening period * Acquired cerebral damage of known etiology * Intact hand skin * Informed consent given by the legal surrogate
Exclusion criteria
* Patients who continuously receive sedative drugs and Na+ or Ca2+ channel blockers (e.g., carbamazepine) or NMDA receptor antagonists (e.g., dextromethorphan) * History of previous serious、progressive neurological disorder prior to the brain injury; * Epilepsy and seizure * Unstable vital signs or life-threatening comorbidities * Implanted devices: including cardiac pacemakers or implantable cardioverter-defibrillators (ICDs), deep brain stimulators, ventriculoperitoneal (VP) shunts, and other indwelling electronic or neurosurgical implants. * Documented pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of consciousness improvement after 14 consecutive days of treatment | 14 days after treatment | The primary effectiveness outcome was the proportion of patients with consciousness improvement after 14 consecutive days of treatment, wherein improvements from unresponsive wakefulness syndrome (UWS)/vegetative state (VS) to minimally conscious state (MCS) or emergence from minimally conscious state (EMCS), from MCS minus (MCS-) to MCS plus (MCS+) or EMCS, or from MCS+ to EMCS signify a consciousness improvement. Diagnoses of UWS/VS, MCS (minus or plus) and EMCS were determined based on the presence of specific Coma Recovery Scale-Revised (CRS-R) subscale items, assessed by a trained neurologist. The hierarchical order of consciousness levels from worst to best is UWS/VS, MCS-, MCS+, and EMCS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Coma Recovery Scale-Revised (CRS-R) scores after 7 days of treatment | 7 days after treatment | CRS-R is composed of six subscales: auditory function, visual function, motor function, oromotor function, communication ability, and arousal level. CRS-R score ranges from 0 to 23, with higher scores mean a better outcome. |
| Changes in sub scale of Coma Recovery Scale-Revised (CRS-R) scores after 7 days of treatment | 7 days after treatment | CRS-R is composed of six subscales: auditory function, visual function, motor function, oromotor function, communication ability, and arousal level. CRS-R score ranges from 0 to 23, with higher scores mean a better outcome. Each sub scale consists of multiple hierarchically organized questions, with higher scores indicating greater performance. |
| Changes in Coma Recovery Scale-Revised (CRS-R) scores after 14 days of treatment | 14 days after treatment | CRS-R is composed of six subscales: auditory function, visual function, motor function, oromotor function, communication ability, and arousal level. CRS-R score ranges from 0 to 23, with higher scores mean a better outcome. |
| Changes in sub scale of Coma Recovery Scale-Revised (CRS-R) scores after 14 days of treatment | 14 days after treatment | CRS-R is composed of six subscales: auditory function, visual function, motor function, oromotor function, communication ability, and arousal level. CRS-R score ranges from 0 to 23, with higher scores mean a better outcome. Each sub scale consists of multiple hierarchically organized questions, with higher scores indicating greater performance. |
| Changes in ABCD model classification after 14 days of treatment | 14 days after treatment | This model classifies the power spectrum of resting-state EEG data into four categories: A, B, C, and D. Type A exhibit a power spectrum peak in the delta range (0-4 Hz), indicative of a completely disconnected thalamocortical network. Type B shows a primary power spectrum peak in the theta range (4-8 Hz), reflecting a severely disconnected thalamocortical network. Type C exhibits power spectrum peaks in both the theta (4-8 Hz) and beta (13-24 Hz) ranges, indicative of a moderately disconnected thalamocortical network. Type D shows power spectrum peaks in the alpha (8-13 Hz) and beta ranges, representing a fully intact thalamocortical network. |
| Functional outcomes measured by the Glasgow Outcome Scale-Extended (GOSE) at 3 months after enrollment | 3 months after enrollment | Functional outcomes were assessed at 3 months after enrollment using the Glasgow Outcome Scale-Extended (GOSE; range 1-8, where higher scores indicate better functional outcomes). |
| Functional outcomes measured by the Glasgow Outcome Scale-Extended (GOSE) at 6 months after enrollment | 6 months after enrollment | Functional outcomes were assessed at 6 months after enrollment using the Glasgow Outcome Scale-Extended (GOSE; range 1-8, where higher scores indicate better functional outcomes). |
| Incidence of adverse events during 6 months after enrollment | 6 months after enrollment | The safety outcome was the incidence of adverse events during 6 months after enrollment. |
| Incidence of severe adverse events during 6 months after enrollment | 6 months after enrollment | The safety outcome was the incidence of severe adverse events during 6 months after enrollment. |
| Incidence of adverse events prespecified for transcutaneous electrical stimulation during treatment | from the first treatment on Day 1 to the completion of the last treatment on Day 14 | The following adverse events are prespecified for transcutaneous electrical stimulation applied to the twelve Jing-Well points of the hand, including treatment intolerance: manifested as observable distress responses during stimulation, (e.g., painful facial expressions, moaning, crying, or involuntary head movements); local adverse effects: skin infection (e.g., redness, swelling, suppuration), subcutaneous ecchymosis, and skin burns (e.g., blistering or eschar formation) at stimulation sites; and systemic adverse effects: epileptic seizures temporally associated with the intervention. |
| Incidence of severe adverse events prespecified for transcutaneous electrical stimulation during treatment | from the first treatment on Day 1 to the completion of the last treatment on Day 14 | The following adverse events are prespecified for transcutaneous electrical stimulation applied to the twelve Jing-Well points of the hand, including treatment intolerance: manifested as observable distress responses during stimulation, (e.g., painful facial expressions, moaning, crying, or involuntary head movements); local adverse effects: skin infection (e.g., redness, swelling, suppuration), subcutaneous ecchymosis, and skin burns (e.g., blistering or eschar formation) at stimulation sites; and systemic adverse effects: epileptic seizures temporally associated with the intervention. Serious adverse events (SAEs) are defined as any untoward medical occurrence that results in death, is life-threatening, requires or prolongs hospitalization, results in persistent or significant disability/incapacity |
Countries
China
Contacts
CONTACTWen Jiang, Dr.
CONTACTZhirong Fan, Dr.
Outcome results
None listed