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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
160
Transcutaneous electrical acupoint stimulation at hand twelve jing-well points
Sham electrical acupoint stimulation at hand twelve jing-well points
Xijing Hospital
Xi'an, Shaanxi, China
Proportion of consciousness improvement after 14 consecutive days of 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.
Time frame: 14 days after treatment
Changes in Coma Recovery Scale-Revised (CRS-R) scores after 7 days of 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.
Time frame: 7 days after treatment
Changes in sub scale of Coma Recovery Scale-Revised (CRS-R) scores after 7 days of 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.
Time frame: 7 days after treatment
Changes in Coma Recovery Scale-Revised (CRS-R) scores after 14 days of 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.
Time frame: 14 days after treatment
Changes in sub scale of Coma Recovery Scale-Revised (CRS-R) scores after 14 days of 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.
Time frame: 14 days after treatment
Changes in ABCD model classification after 14 days of 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.
Time frame: 14 days after treatment
Functional outcomes measured by the Glasgow Outcome Scale-Extended (GOSE) at 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).
Time frame: 3 months after enrollment
Functional outcomes measured by the Glasgow Outcome Scale-Extended (GOSE) at 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).
Time frame: 6 months after enrollment
Incidence of adverse events during 6 months after enrollment
The safety outcome was the incidence of adverse events during 6 months after enrollment.
Time frame: 6 months after enrollment
Incidence of severe adverse events during 6 months after enrollment
The safety outcome was the incidence of severe adverse events during 6 months after enrollment.
Time frame: 6 months after enrollment
Incidence of adverse events prespecified for transcutaneous electrical stimulation during treatment
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.
Time frame: from the first treatment on Day 1 to the completion of the last treatment on Day 14
Incidence of severe adverse events prespecified for transcutaneous electrical stimulation during treatment
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
Time frame: from the first treatment on Day 1 to the completion of the last treatment on Day 14
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